{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T04:40:58Z","timestamp":1760676058525,"version":"build-2065373602"},"reference-count":131,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T00:00:00Z","timestamp":1760486400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Federal Agency of Scientific Organizations of Russia","award":["No. 075-00263-25-00"],"award-info":[{"award-number":["No. 075-00263-25-00"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>As we found earlier, paxilline (a Penicillium paxilli mycotoxin and blocker of Ca2+-activated big-conductance potassium channels, BK(Ca)s) attenuated Cd2+-induced cytotoxic effects, whereas BK(Ca) activators (NS004, NS1619) and Cd2+ were able to induce apoptosis, which was enhanced when used together. In this work, molecular mechanisms underlying the aforementioned effects were studied using two rat cell lines, PC12 and AS-30D, flow cytometry, and spectrofluorometric and polarographic techniques. Both NS004 and NS1619 were found to have time- and dose-dependent effects on cell viability, respiration, mitochondrial membrane potential, and intracellular reactive oxygen species (ROS) production. In PC12 cells, BK(Ca) openers exerted an uncoupling effect after 3 h, increasing the resting respiration, while they partially inhibited the maximal respiration after 5 and 24 h; in addition, after 3 h, a transient protection by NS004\/NS1619 against Cd2+-induced decrease of cell viability was observed. In both cell types, NS004\/NS1619 increased ROS production after 3 h and counteracted the mitigating effect of paxilline against Cd2+-induced necrosis. In turn, paxilline reduced NS004\/NS1619-induced apoptosis in AS-30D cells and ROS increase produced by NS004\/NS1619 and\/or Cd2+ in PC12 cells. As a result, the involvement of the mitochondrial respiratory chain, ROS, and, very likely, BK(Ca)s, in the mechanisms of the modulatory effects of the BK(Ca) blocker\/opener(s) used in the absence and presence of Cd2+ was revealed.<\/jats:p>","DOI":"10.3390\/ijms262010048","type":"journal-article","created":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T14:04:02Z","timestamp":1760537042000},"page":"10048","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Application of Modulators of Ca2+-Activated Big-Conductance Potassium Channels Against Cd2+-Induced Cytotoxicity: A Study on Two Rat Cell Lines, PC12 and AS-30D"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3663-3881","authenticated-orcid":false,"given":"Elena A.","family":"Belyaeva","sequence":"first","affiliation":[{"name":"Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 44 Thorez Avenue, Saint-Petersburg 194223, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatyana V.","family":"Sokolova","sequence":"additional","affiliation":[{"name":"Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 44 Thorez Avenue, Saint-Petersburg 194223, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Nordberg, G.F., and Costa, M. (2022). Chapter 7\u2014Cadmium. Handbook on the Toxicology of Metals, Academic Press. [5th ed.].","DOI":"10.1016\/B978-0-12-822946-0.00006-4"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1007\/s40572-022-00371-7","article-title":"Environmental Chemical Exposures and Mitochondrial Dysfunction: A Review of Recent Literature","volume":"9","author":"Reddam","year":"2022","journal-title":"Curr. Environ. Health Rep."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Koyama, H., Kamogashira, T., and Yamasoba, T. (2024). Heavy Metal Exposure: Molecular Pathways, Clinical Implications, and Protective Strategies. Antioxidants, 13.","DOI":"10.3390\/antiox13010076"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Davidova, S., Milushev, V., and Satchanska, G. (2024). The Mechanisms of Cadmium Toxicity in Living Organisms. Toxics, 12.","DOI":"10.20944\/preprints202410.1332.v1"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.jtemb.2016.12.012","article-title":"Lead, cadmium and mercury in cerebrospinal fluid and risk of amyotrophic lateral sclerosis: A case-control study","volume":"43","author":"Vinceti","year":"2017","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Tassone, G., Kola, A., Valensin, D., and Pozzi, C. (2021). Dynamic Interplay Between Copper Toxicity and Mitochondrial Dysfunction in Alzheimer\u2019s Disease. Life, 11.","DOI":"10.3390\/life11050386"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Arruebarrena, M.A., Hawe, C.T., Lee, Y.M., and Branco, R.C. (2023). Mechanisms of Cadmium Neurotoxicity. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242316558"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4459","DOI":"10.1007\/s12011-023-04041-z","article-title":"Inflammation in Metal-Induced Neurological Disorders and Neurodegenerative Diseases","volume":"202","author":"Wei","year":"2024","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"349","DOI":"10.2131\/jts.49.349","article-title":"Protection of cultured vascular endothelial cells against cadmium cytotoxicity by simultaneous treatment or pretreatment with manganese","volume":"49","author":"Fujie","year":"2024","journal-title":"J. Toxicol. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"116254","DOI":"10.1016\/j.ecoenv.2024.116254","article-title":"In vivo chronic exposure to inorganic mercury worsens hypercholesterolemia, oxidative stress and atherosclerosis in the LDL receptor knockout mice","volume":"275","author":"Queiroz","year":"2024","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/s00204-024-03903-2","article-title":"Heavy metals: Toxicity and human health effects","volume":"99","author":"Jomova","year":"2025","journal-title":"Arch. Toxicol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.taap.2008.03.017","article-title":"Mitochondria as an important target in heavy metal toxicity in rat hepatoma AS-30D cells","volume":"231","author":"Belyaeva","year":"2008","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"S63","DOI":"10.1016\/j.jtemb.2010.10.007","article-title":"In vitro modulation of heavy metal-induced rat liver mitochondria dysfunction: A comparison of copper and mercury with cadmium","volume":"25","author":"Belyaeva","year":"2011","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"136063","DOI":"10.1100\/2012\/136063","article-title":"Mitochondrial electron transport chain in heavy metal-induced neurotoxicity: Effects of cadmium, mercury, and copper","volume":"2012","author":"Belyaeva","year":"2012","journal-title":"Sci. World J."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Buha, A., Matovic, V., Antonijevic, B., Bulat, Z., Curcic, M., Renieri, E.A., Tsatsakis, A.M., Schweitzer, A., and Wallace, D. (2018). Overview of Cadmium Thyroid Disrupting Effects and Mechanisms. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19051501"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"139181","DOI":"10.1016\/j.jhazmat.2025.139181","article-title":"Secondary target organs exhibit differential ability to clear cadmium after cadmium oxide nanoparticle inhalation","volume":"496","author":"Alexa","year":"2025","journal-title":"J. Hazard. Mater."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"105101","DOI":"10.1016\/j.tiv.2021.105101","article-title":"Underlying mechanisms of cytotoxicity in HepG2 hepatocarcinoma cells exposed to arsenic, cadmium and mercury individually and in combination","volume":"72","author":"Cordier","year":"2021","journal-title":"Toxicol. Vitr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"105015","DOI":"10.1016\/j.tiv.2020.105015","article-title":"Effects of environmental metals on mitochondrial bioenergetics of the CD-1 mice pancreatic beta-cells","volume":"70","author":"Elmorsy","year":"2021","journal-title":"Toxicol. Vitr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"153339","DOI":"10.1016\/j.tox.2022.153339","article-title":"The mechanism of the cadmium-induced toxicity and cellular response in the liver","volume":"480","year":"2022","journal-title":"Toxicology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"153136","DOI":"10.1016\/j.tox.2022.153136","article-title":"Heavy metals induced mitochondrial dysfunction in animals: Molecular mechanism of toxicity","volume":"469","author":"Sun","year":"2022","journal-title":"Toxicology"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Korotkov, S.M. (2023). Mitochondrial Oxidative Stress Is the General Reason for Apoptosis Induced by Different-Valence Heavy Metals in Cells and Mitochondria. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241914459"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Qu, F., and Zheng, W. (2024). Cadmium Exposure: Mechanisms and Pathways of Toxicity and Implications for Human Health. Toxics, 12.","DOI":"10.3390\/toxics12060388"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1007\/s00204-020-02692-8","article-title":"Cell organelles as targets of mammalian cadmium toxicity","volume":"94","author":"Lee","year":"2020","journal-title":"Arch. Toxicol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1023\/A:1010607307099","article-title":"Bivalent metal ions modulate Cd2+ effects on isolated rat liver mitochondria","volume":"33","author":"Belyaeva","year":"2001","journal-title":"J. Bioenerg. Biomembr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/S0003-9861(02)00400-9","article-title":"Cyclosporin A-sensitive permeability transition pore is involved in Cd2+-induced dysfunction of isolated rat liver mitochondria: Doubts no more","volume":"405","author":"Belyaeva","year":"2002","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/S0041-008X(03)00255-2","article-title":"Mechanism of primary Cd2+-induced rat liver mitochondria dysfunction: Discrete modes of Cd2+ action on calcium and thiol-dependent domains","volume":"192","author":"Belyaeva","year":"2003","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.cbi.2004.09.019","article-title":"Cd2+ versus Ca2+-produced mitochondrial membrane permeabilization: A proposed direct participation of respiratory complexes I and III","volume":"150","author":"Belyaeva","year":"2004","journal-title":"Chem. Biol. Interact."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1146\/annurev-biophys-092622-094853","article-title":"Mitochondrial Ion Channels","volume":"52","author":"Szabo","year":"2023","journal-title":"Annu. Rev. Biophys."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Tommasin, L., Carrer, A., Nata, F.B., Frigo, E., Fogolari, F., Lippe, G., Carraro, M., and Bernardi, P. (2025). Adenine nucleotide translocator and ATP synthase cooperate in mediating the mitochondrial permeability transition. J. Physiol.","DOI":"10.1113\/JP287147"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"545","DOI":"10.18388\/abp.2004_3590","article-title":"Cd2+-promoted mitochondrial permeability transition: A comparison with other heavy metals","volume":"51","author":"Belyaeva","year":"2004","journal-title":"Acta Biochim. Pol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Belyaeva, E.A., Emelyanova, L.V., Korotkov, S.M., Brailovskaya, I.V., and Savina, M.V. (2014). On the mechanism(s) of membrane permeability transition in liver mitochondria of lamprey, Lampetra fluviatilis L.: Insights from cadmium. Biomed. Res. Int., 2014.","DOI":"10.1155\/2014\/691724"},{"key":"ref_32","first-page":"105","article-title":"Mechanism(s) of Membrane Permeability Transition in Liver Mitochondria of Lamprey, Lampetra fluviatilis L. during Pre-spawning Starvation","volume":"Volume 16","author":"Elshimali","year":"2021","journal-title":"Recent Developments in Medicine and Medical Research"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1134\/S0022093013050046","article-title":"Effect of diazoxide on AS-30D rat ascites hepatoma cells treated by Cd2+","volume":"49","author":"Belyaeva","year":"2013","journal-title":"J. Evol. Biochem. Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"114829","DOI":"10.1016\/j.ecoenv.2023.114829","article-title":"Modulators of mitochondrial ATP-sensitive potassium channel affect cytotoxicity of heavy metals: Action on isolated rat liver mitochondria and AS-30D ascites hepatoma cells","volume":"256","author":"Belyaeva","year":"2023","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"110519","DOI":"10.1016\/j.ecoenv.2020.110519","article-title":"Mitigating effect of paxilline against injury produced by Cd2+ in rat pheochromocytoma PC12 and ascites hepatoma AS-30D cells","volume":"196","author":"Belyaeva","year":"2020","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Sancho, M., and Kyle, B.D. (2021). The Large-Conductance, Calcium-Activated Potassium Channel: A Big Key Regulator of Cell Physiology. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.750615"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.2174\/1570159X21666221208091805","article-title":"KCa-Related Neurological Disorders: Phenotypic Spectrum and Therapeutic Indications","volume":"21","author":"Zahra","year":"2023","journal-title":"Curr. Neuropharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1568","DOI":"10.1016\/j.bbabio.2006.09.006","article-title":"Reactive oxygen species produced by the mitochondrial respiratory chain are involved in Cd2+-induced injury of rat ascites hepatoma AS-30D cells","volume":"1757","author":"Belyaeva","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Belyaeva, E.A. (2010). Stigmatellin as a modulator of metal-induced inner mitochondrial membrane permeabilization. Biochim. Biophys. Acta Bioenerg., 1797.","DOI":"10.1016\/j.bbabio.2010.04.239"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"435","DOI":"10.18388\/abp.2010_2430","article-title":"Mitochondrial respiratory chain inhibitors modulate the metal-induced inner mitochondrial membrane permeabilization","volume":"57","author":"Belyaeva","year":"2010","journal-title":"Acta Biochim. Pol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.jtemb.2018.06.009","article-title":"Respiratory complex II in mitochondrial dysfunction-mediated cytotoxicity: Insight from cadmium","volume":"50","author":"Belyaeva","year":"2018","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"105264","DOI":"10.1016\/j.aquatox.2019.105264","article-title":"Effects of bioenergetics, temperature and cadmium on liver mitochondria reactive oxygen species production and consumption","volume":"214","author":"Okoye","year":"2019","journal-title":"Aquat. Toxicol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Branca, J.J.V., Pacini, A., Gulisano, M., Taddei, N., Fiorillo, C., and Becatti, M. (2020). Cadmium-induced cytotoxicity: Effects on mitochondrial electron transport chain. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.604377"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"144","DOI":"10.9734\/bpi\/cerb\/v2\/17514D","article-title":"Role of Mitochondrial Respiratory Chain in Neurotoxic Action of Heavy Metals: Comparison of Cd2+, Hg2+ and Cu2+","volume":"2","author":"Belyaeva","year":"2022","journal-title":"Cut. Edge Res. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"de Lira-S\u00e1nchez, J.A., Esparza-Perusqu\u00eda, M., Mart\u00ednez, F., Pardo, J.P., and Flores-Herrera, O. (2023). Heavy metals do not induce ROS production by mitochondrial respirasome. Biochim. Biophys. Acta Bioenerg., 1864.","DOI":"10.1016\/j.bbabio.2023.148999"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"100750","DOI":"10.1016\/j.jlr.2025.100750","article-title":"Cadmium-cardiolipin disruption of respirasome assembly and redox balance through mitochondrial membrane rigidification","volume":"66","author":"Romanova","year":"2025","journal-title":"J. Lipid Res."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Gonz\u00e1lez-Sanabria, N., Echeverr\u00eda, F., Segura, I., Alvarado-S\u00e1nchez, R., and Latorre, R. (2021). BK in Double-Membrane Organelles: A Biophysical, Pharmacological, and Functional Survey. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.761474"},{"key":"ref_48","first-page":"133","article-title":"Cd(II)-induced cytotoxicity is attenuated by K+ channels modulators","volume":"Volume 11","author":"Pele","year":"2011","journal-title":"Metal Ions in Biology and Medicine"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1134\/S0022093015040018","article-title":"The effect of modulators of large-conductance Ca2+-modulated K+ channels on rat AS-30D ascites hepatoma cells and isolated liver mitochondria treated with Cd2+","volume":"51","author":"Belyaeva","year":"2015","journal-title":"J. Evol. Biochem. Physiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"121433","DOI":"10.1016\/j.lfs.2023.121433","article-title":"Role of organellar Ca2+-activated K+ channels in disease development","volume":"316","author":"Jiang","year":"2023","journal-title":"Life Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.bbrc.2008.07.161","article-title":"The potassium ion channel opener NS1619 inhibits proliferation and induces apoptosis in A2780 ovarian cancer cells","volume":"375","author":"Han","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_52","first-page":"27","article-title":"Large-conductance K+ channel openers induce death of human glioma cells","volume":"60","author":"Godlewski","year":"2009","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1007\/s12035-013-8467-x","article-title":"Activation of BKca channels mediates hippocampal neuronal death after reoxygenation and reperfusion","volume":"48","author":"Chen","year":"2013","journal-title":"Mol. Neurobiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.intimp.2014.06.040","article-title":"Big Potassium (BK) ion channels in biology, disease and possible targets for cancer immunotherapy","volume":"22","author":"Ge","year":"2014","journal-title":"Int. Immunopharmacol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Augustynek, B., Koprowski, P., Rotko, D., Kunz, W.S., Szewczyk, A., and Kulawiak, B. (2018). Mitochondrial BK Channel Openers CGS7181 and CGS7184 Exhibit Cytotoxic Properties. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19020353"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Van, N.T.H., Kim, W.K., and Nam, J.H. (2024). Challenges in the Therapeutic Targeting of KCa Channels: From Basic Physiology to Clinical Applications. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25052965"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Wrzosek, A., Ga\u0142ecka, S., \u017bochowska, M., Olszewska, A., and Kulawiak, B. (2022). Alternative Targets for Modulators of Mitochondrial Potassium Channels. Molecules, 27.","DOI":"10.3390\/molecules27010299"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.mito.2011.12.001","article-title":"Glutamate-induced cell death in HT22 mouse hippocampal cells is attenuated by paxilline, a BK channel inhibitor","volume":"12","author":"Kulawiak","year":"2012","journal-title":"Mitochondrion"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/j.mito.2013.07.077","article-title":"Cd2+-induced injury of rat ascites hepatoma AS-30D cells: A possible involvement of Ca2+-activated large-conductance potassium channels","volume":"13","author":"Belyaeva","year":"2013","journal-title":"Mitochondrion"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Belyaeva, E.A., and Sokolova, T.V. (2020). Mechanism(s) of Modulation of Cd2+-Induced Cytotoxicity by Paxilline and NS1619\/NS004: An Involvement of Ca2+-Activated Big-Conductance Potassium Channel and\/or Respiratory Chain of Mitochondria?. Zh. Evol. Biokhim. Fiziol., 56.","DOI":"10.31857\/S0044452920071523"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1016\/j.freeradbiomed.2010.12.032","article-title":"Cadmium induction of reactive oxygen species activates the mTOR pathway, leading to neuronal cell death","volume":"50","author":"Chen","year":"2011","journal-title":"Free Radic. Biol. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/s12011-014-9918-6","article-title":"Cadmium induces PC12 cells apoptosis via an extracellular signal-regulated kinase and c-Jun N-terminal kinase-mediated mitochondrial apoptotic pathway","volume":"158","author":"Jiang","year":"2014","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.cbi.2017.04.003","article-title":"Cytotoxic effects of cadmium and zinc co-exposure in PC12 cells and the underlying mechanism","volume":"269","author":"Rahman","year":"2017","journal-title":"Chem. Biol. Interact."},{"key":"ref_64","first-page":"130","article-title":"Impact of Zn2+ and selenite on rat ascites hepatoma AS-30D cells and rat liver mitochondria: A comparison with Cd2+, Hg2+, Cu2+, and Ca2+","volume":"Volume 10","author":"Turkmen","year":"2025","journal-title":"Recent Developments in Chemistry and Biochemistry Research"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Shah, N., Saxena, B., and Gupta, R. (2025). Mitochondria: Key Mediator for Environmental Toxicant-Induced Neurodegeneration. Int. J. Toxicol., 10915818251369414.","DOI":"10.1177\/10915818251369414"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Szewczyk, A., Bednarczyk, P., Kulawiak, B., \u017bochowska, M., Kalenik, B., Lewandowska, J., Pytlak, K., Ga\u0142ecka, S., Wrzosek, A., and Koprowski, P. (2025). Mitochondrial potassium channels: New properties and functions. Biochim. Biophys. Acta Bioenerg., 1866.","DOI":"10.1016\/j.bbabio.2025.149546"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.cyto.2005.09.008","article-title":"The mitochondrial permeability transition pore and the Ca2+-activated K+ channel contribute to the cardioprotection conferred by tumor necrosis factor-alpha","volume":"32","author":"Gao","year":"2005","journal-title":"Cytokine"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"H434","DOI":"10.1152\/ajpheart.00763.2005","article-title":"Cardiac mitochondrial preconditioning by Big Ca2+-sensitive K+ channel opening requires superoxide radical generation","volume":"290","author":"Stowe","year":"2006","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"H1400","DOI":"10.1152\/ajpheart.00198.2007","article-title":"Reverse electron flow-induced ROS production is attenuated by activation of mitochondrial Ca2+-sensitive K+ channels","volume":"293","author":"Heinen","year":"2007","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1159\/000149790","article-title":"Hypoxia increases activity of the BK-channel in the inner mitochondrial membrane and reduces activity of the permeability transition pore","volume":"22","author":"Cheng","year":"2008","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.expneurol.2008.05.004","article-title":"BK channel openers inhibit ROS production of isolated rat brain mitochondria","volume":"212","author":"Kulawiak","year":"2008","journal-title":"Exp. Neurol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1016\/j.febslet.2009.12.038","article-title":"Interaction of mitochondrial potassium channels with the permeability transition pore","volume":"584","author":"Cheng","year":"2010","journal-title":"FEBS Lett."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1159\/000327944","article-title":"Activation of the permeability transition pore by Bax via inhibition of the mitochondrial BK channel","volume":"27","author":"Cheng","year":"2011","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1097\/FJC.0000000000000524","article-title":"Endogenous and Agonist-induced Opening of Mitochondrial Big Versus Small Ca2+-sensitive K+ Channels on Cardiac Cell and Mitochondrial Protection","volume":"70","author":"Stowe","year":"2017","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Goswami, S.K., Ponnalagu, D., Hussain, A.T., Shah, K., Karekar, P., Gururaja Rao, S., Meredith, A.L., Khan, M., and Singh, H. (2019). Expression and Activation of BKCa Channels in Mice Protects Against Ischemia-Reperfusion Injury of Isolated Hearts by Modulating Mitochondrial Function. Front. Cardiovasc. Med., 5.","DOI":"10.3389\/fcvm.2018.00194"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"6023","DOI":"10.1073\/pnas.1920008117","article-title":"Loss-of-function BK channel mutation causes impaired mitochondria and progressive cerebellar ataxia","volume":"117","author":"Du","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"H625","DOI":"10.1152\/ajpheart.00818.2014","article-title":"BKCa channel activation increases cardiac contractile recovery following hypothermic ischemia\/reperfusion","volume":"309","author":"Cordeiro","year":"2015","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1177\/1535370212474596","article-title":"Pharmacological activation of mitochondrial BKCa channels protects isolated cardiomyocytes against simulated reperfusion-induced injury","volume":"238","author":"Borchert","year":"2013","journal-title":"Exp. Biol. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.molcel.2016.05.040","article-title":"Redox Nanodomains Are Induced by and Control Calcium Signaling at the ER-Mitochondrial Interface","volume":"63","author":"Booth","year":"2016","journal-title":"Mol. Cell"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.ceca.2017.07.005","article-title":"Mitochondrial Ca2+-activated K+ channels and their role in cell life and death pathways","volume":"69","author":"Krabbendam","year":"2018","journal-title":"Cell Calcium"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1016\/S0006-2952(03)00180-1","article-title":"Large-conductance K+ channel openers NS1619 and NS004 as inhibitors of mitochondrial function in glioma cells","volume":"65","author":"Debska","year":"2003","journal-title":"Biochem. Pharmacol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1080\/15376520490257482","article-title":"Large-Conductance Potassium Cation Channel Opener NS1619 Inhibits Cardiac Mitochondria Respiratory Chain","volume":"14","author":"Kicinska","year":"2004","journal-title":"Toxicol. Mech. Methods"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1111\/j.1471-4159.2007.05210.x","article-title":"Delayed neuronal preconditioning by NS1619 is independent of calcium activated potassium channels","volume":"105","author":"Katakam","year":"2008","journal-title":"J. Neurochem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.ejphar.2016.05.039","article-title":"SERCA, complex I of the respiratory chain and ATP-synthase inhibition are involved in pleiotropic effects of NS1619 on endothelial cells","volume":"786","author":"Skup","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"ref_85","first-page":"A20427","article-title":"Activation of large-conductance Ca2+-activated K+ channels (BK) during ischemic cardioplegic arrest (CP) promotes formation of mitochondrial supercomplexes and enhanced mitochondrial respiration","volume":"130","author":"Cordeiro","year":"2014","journal-title":"Circulation"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"20","DOI":"10.21307\/ane-2017-002","article-title":"Effectors of large-conductance calcium-activated potassium channel modulate glutamate excitotoxicity in organotypic hippocampal slice cultures","volume":"76","author":"Szewczyk","year":"2016","journal-title":"Acta Neurobiol. Exp."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Shrum, S., Rusch, N.J., and MacMillan-Crow, L.A. (2019). Specific BK Channel Activator NS11021 Protects Rat Renal Proximal Tubular Cells from Cold Storage-Induced Mitochondrial Injury In Vitro. Biomolecules, 9.","DOI":"10.3390\/biom9120825"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.bbabio.2009.08.002","article-title":"Energetic performance is improved by specific activation of K+ fluxes through KCa channels in heart mitochondria","volume":"1797","author":"Aon","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1134\/S1990747823030066","article-title":"Benzimidazole Derivative NS1619 Inhibits Functioning of Mitochondria Isolated from Mouse Skeletal Muscle","volume":"17","author":"Dubinin","year":"2023","journal-title":"Biochem. Moscow Suppl. Ser. A"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Dubinin, M.V., Starinets, V.S., Belosludtseva, N.V., Mikheeva, I.B., Chelyadnikova, Y.A., Igoshkina, A.D., Vafina, A.B., Vedernikov, A.A., and Belosludtsev, K.N. (2022). BKCa Activator NS1619 Improves the Structure and Function of Skeletal Muscle Mitochondria in Duchenne Dystrophy. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14112336"},{"key":"ref_91","first-page":"189","article-title":"Effect of Large-Conductance Calcium-Dependent K+ Channel Activator NS1619 on Function of Mitochondria in the Heart of Dystrophin-Deficient Mice","volume":"88","author":"Dubinin","year":"2023","journal-title":"Biochemistry"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1152\/ajpheart.00016.2005","article-title":"Cardioprotective effects of estradiol include the activation of large-conductance Ca2+-activated K+ channels in cardiac mitochondria","volume":"289","author":"Ohya","year":"2005","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Bednarczyk, P., Wieckowski, M.R., Broszkiewicz, M., Skowronek, K., Siemen, D., and Szewczyk, A. (2013). Putative Structural and Functional Coupling of the Mitochondrial BKCa Channel to the Respiratory Chain. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0068125"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.mito.2016.08.017","article-title":"The mitochondrial BKCa channel cardiac interactome reveals BKCa association with the mitochondrial import receptor subunit Tom22, and the adenine nucleotide translocator","volume":"33","author":"Zhang","year":"2017","journal-title":"Mitochondrion"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1089\/ars.2022.0173","article-title":"Mitochondrial Cristae Morphology Reflecting Metabolism, Superoxide Formation, Redox Homeostasis, and Pathology","volume":"39","year":"2023","journal-title":"Antioxid. Redox Signal."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.cell.2013.08.032","article-title":"Mitochondrial cristae shape determines respiratory chain supercomplexes assembly and respiratory efficiency","volume":"155","author":"Cogliati","year":"2013","journal-title":"Cell"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1093\/brain\/awm335","article-title":"OPA1 mutations associated with dominant optic atrophy impair oxidative phosphorylation and mitochondrial fusion","volume":"131","author":"Zanna","year":"2008","journal-title":"Brain"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1161\/CIRCRESAHA.124.325477","article-title":"Pharmacological Enhancement of Small Conductance Ca2+-Activated K+ Channels Suppresses Cardiac Arrhythmias in a Mouse Model of Catecholaminergic Polymorphic Ventricular Tachycardia","volume":"137","author":"Veress","year":"2025","journal-title":"Circ. Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"e70776","DOI":"10.1096\/fj.202500707RR","article-title":"KCNH6 Potassium Channel Regulates Assembling of Mitochondrial Complex I and Promotes Insulin Secretion in Islet Beta Cells","volume":"39","author":"Han","year":"2025","journal-title":"FASEB J."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Cui, J. (2021). BK Channel Gating Mechanisms: Progresses Toward a Better Understanding of Variants Linked Neurological Diseases. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.762175"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1016\/S0006-3495(97)78168-2","article-title":"A novel calcium-sensing domain in the BK channel","volume":"73","author":"Schreiber","year":"1997","journal-title":"Biophys. J."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1038\/nature00956","article-title":"Multiple regulatory sites in large-conductance calcium-activated potassium channels","volume":"418","author":"Xia","year":"2002","journal-title":"Nature"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1085\/jgp.200409239","article-title":"Divalent cation sensitivity of BK channel activation supports the existence of three distinct binding sites","volume":"125","author":"Zeng","year":"2005","journal-title":"J. Gen. Physiol."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Ram\u00edrez-Camacho, I., Garc\u00eda-Ni\u00f1o, W.R., Flores-Garc\u00eda, M., Pedraza-Chaverri, J., and Zazueta, C. (2020). Alteration of mitochondrial supercomplexes assembly in metabolic diseases. Biochim. Biophys. Acta Mol. Basis Dis., 1866.","DOI":"10.1016\/j.bbadis.2020.165935"},{"key":"ref_105","first-page":"71","article-title":"Regulated mitochondrial permeability transition: A possible involvement of mitochondrial respiratory complexes I and III","volume":"4","author":"Belyaeva","year":"2004","journal-title":"Mitochondrion"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s00232-011-9361-y","article-title":"Spectroscopic and microscopic studies on the mechanisms of mitochondrial toxicity induced by different concentrations of cadmium","volume":"241","author":"Zhang","year":"2011","journal-title":"J. Membr. Biol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.jinorgbio.2016.11.023","article-title":"Quercetin loading CdSe\/ZnS nanoparticles as efficient antibacterial and anticancer materials","volume":"167","author":"Yang","year":"2017","journal-title":"J. Inorg. Biochem."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Al-Hasawi, N.A., Amine, S.A., and Novotny, L. (2018). The In Vitro Anti-Proliferative Interaction of Flavonoid Quercetin and Toxic Metal Cadmium in the 1321N1 Human Astrocytoma Cell Line. Sci. Pharm., 86.","DOI":"10.3390\/scipharm86030036"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1002\/ptr.6503","article-title":"A systematic review on hepatoprotective activity of quercetin against various drugs and toxic agents: Evidence from preclinical studies","volume":"34","author":"Pingili","year":"2020","journal-title":"Phytother. Res."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Capriglione, F., Maiuolo, J., Celano, M., Damante, G., Russo, D., Bulotta, S., and Maggisano, V. (2021). Quercetin Protects Human Thyroid Cells against Cadmium Toxicity. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22136849"},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Wang, J., Wang, K., Ding, L., Zhao, P., Zhang, C., Wang, H., Yang, Z., and Liu, Z. (2022). Alleviating effect of quercetin on cadmium-induced oxidative damage and apoptosis by activating the Nrf2-keap1 pathway in BRL-3A cells. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.969892"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"107561","DOI":"10.1016\/j.toxicon.2023.107561","article-title":"Roles of Cyt-c\/Caspase-9\/Caspase-3\/Bax\/Bcl-2 pathway in Cd-induced testicular injury in rats and the protective effect of quercetin","volume":"237","author":"Yu","year":"2024","journal-title":"Toxicon"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Seo, S.Y., Ju, W.S., Kim, K., Kim, J., Yu, J.O., Ryu, J.S., Kim, J.S., Lee, H.A., Koo, D.B., and Choo, Y.K. (2024). Quercetin Induces Mitochondrial Apoptosis and Downregulates Ganglioside GD3 Expression in Melanoma Cells. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25105146"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"235101","DOI":"10.1088\/1361-6528\/add6ad","article-title":"Tumor microenvironment-responsive diagnosis and treatment of integrated drug-loaded CdTe quantum dots for treatment tumors","volume":"36","author":"Su","year":"2025","journal-title":"Nanotechnology"},{"key":"ref_115","first-page":"e42682","article-title":"Phytochemical insights into flavonoids in cancer: Mechanisms, therapeutic potential, and the case of quercetin","volume":"1","author":"Canales","year":"2025","journal-title":"Heliyon"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1016\/j.bbabio.2009.06.002","article-title":"Quercetin can act either as an inhibitor or an inducer of the mitochondrial permeability transition pore: A demonstration of the ambivalent redox character of polyphenols","volume":"1787","author":"Biasutto","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1038\/sj.bjp.0703397","article-title":"Inhibition of mitochondrial proton F0F1-ATPase\/ATP synthase by polyphenolic phytochemicals","volume":"130","author":"Zheng","year":"2000","journal-title":"Br. J. Pharmacol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1562","DOI":"10.1016\/j.bbabio.2011.09.022","article-title":"Complex I and cytochrome C are molecular targets of flavonoids that inhibit hydrogen peroxide production by mitochondria","volume":"1807","author":"Lagoa","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.cbi.2012.05.006","article-title":"Inhibition of mitochondrial complex I by various non-steroidal anti-inflammatory drugs and its protection by quercetin via a coenzyme Q-like action","volume":"199","author":"Aliaga","year":"2012","journal-title":"Chem. Biol. Interact."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Dabrowska, A., Zajac, M., Bednarczyk, P., and Lukasiak, A. (2022). Effect of Quercetin on mitoBKCa Channel and Mitochondrial Function in Human Bronchial Epithelial Cells Exposed to Particulate Matter. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24010638"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.mito.2022.04.005","article-title":"Flavonoid quercetin abolish paxilline inhibition of the mitochondrial BKCa channel","volume":"65","author":"Kampa","year":"2022","journal-title":"Mitochondrion"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1016\/0028-3908(96)00137-2","article-title":"Paxilline inhibition of the alpha-subunit of the high-conductance calcium-activated potassium channel","volume":"35","author":"Sanchez","year":"1996","journal-title":"Neuropharmacology"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1073\/pnas.1912623117","article-title":"The functionally relevant site for paxilline inhibition of BK channels","volume":"117","author":"Zhou","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/S0014-2999(00)00775-5","article-title":"The mycotoxin paxilline inhibits the cerebellar inositol 1,4,5-trisphosphate receptor","volume":"408","author":"Longland","year":"2000","journal-title":"Eur. J. Pharmacol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/S0003-9861(02)00240-0","article-title":"The mechanism of inhibition of the sarco\/endoplasmic reticulum Ca2+-ATPase by paxilline","volume":"406","author":"Bilmen","year":"2002","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Kamitsuka, P.J., Ghanem, M.M., Ziar, R., McDonald, S.E., Thomas, M.G., and Kwakye, G.F. (2023). Defective Mitochondrial Dynamics and Protein Degradation Pathways Underlie Cadmium-Induced Neurotoxicity and Cell Death in Huntington\u2019s Disease Striatal Cells. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24087178"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s13530-024-00243-7","article-title":"A comprehensive review of cadmium-induced toxicity, signalling pathways, and potential mitigation strategies","volume":"17","author":"Vijiyakumar","year":"2025","journal-title":"Toxicol. Environ. Health Sci."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Lee, J.Y., Tokumoto, M., and Satoh, M. (2025). Molecular Mechanisms of Cadmium-Induced Toxicity and Its Modification. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26157515"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.bbamcr.2005.12.009","article-title":"Short-term and long-term effects of fatty acids in rat hepatoma AS-30D cells: The way to apoptosis","volume":"1763","author":"Dymkowska","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Sivandzade, F., Bhalerao, A., and Cucullo, L. (2019). Analysis of the Mitochondrial Membrane Potential Using the Cationic JC-1 Dye as a Sensitive Fluorescent Probe. Bio Protoc., 9.","DOI":"10.21769\/BioProtoc.3128"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/0022-1759(91)90198-O","article-title":"A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry","volume":"139","author":"Nicoletti","year":"1991","journal-title":"J. Immunol. Methods"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/20\/10048\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T04:23:39Z","timestamp":1760675019000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/20\/10048"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,15]]},"references-count":131,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["ijms262010048"],"URL":"https:\/\/doi.org\/10.3390\/ijms262010048","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2025,10,15]]}}}