{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T01:51:46Z","timestamp":1793152306660,"version":"4.5.0"},"reference-count":56,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T00:00:00Z","timestamp":1610668800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001843","name":"Science and Engineering Research Board","doi-asserted-by":"publisher","award":["EMR\/2016\/005644"],"award-info":[{"award-number":["EMR\/2016\/005644"]}],"id":[{"id":"10.13039\/501100001843","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001409","name":"Department of Science and Technology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["DST\/CSRI\/2018\/247"],"award-info":[{"award-number":["DST\/CSRI\/2018\/247"]}],"id":[{"id":"10.13039\/501100001409","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["National bioscience award"],"award-info":[{"award-number":["National bioscience award"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Severe malaria caused by Plasmodium falciparum poses a major global health problem with high morbidity and mortality. P. falciparum harbors a family of pore-forming proteins (PFPs), known as perforin like proteins (PLPs), which are structurally equivalent to prokaryotic PFPs. These PLPs are secreted from the parasites and, they contribute to disease pathogenesis by interacting with host cells. The severe malaria pathogenesis is associated with the dysfunction of various barrier cells, including endothelial cells (EC). Several factors, including PLPs secreted by parasites, contribute to the host cell dysfunction. Herein, we have tested the hypothesis that PLPs mediate dysfunction of barrier cells and might have a role in disease pathogenesis. We analyzed various dysfunctions in barrier cells following rPLP2 exposure and demonstrate that it causes an increase in intracellular Ca2+ levels. Additionally, rPLP2 exposed barrier cells displayed features of cell death, including Annexin\/PI positivity, depolarized the mitochondrial membrane potential, and ROS generation. We have further performed the time-lapse video microscopy of barrier cells and found that the treatment of rPLP2 triggers their membrane blebbing. The cytoplasmic localization of HMGB1, a marker of necrosis, further confirmed the necrotic type of cell death. This study highlights the role of parasite factor PLP in endothelial dysfunction and provides a rationale for the design of adjunct therapies against severe malaria.<\/jats:p>","DOI":"10.3390\/toxins13010062","type":"journal-article","created":{"date-parts":[[2021,1,21]],"date-time":"2021-01-21T02:36:05Z","timestamp":1611196565000},"page":"62","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Pathogenic Pore Forming Proteins of Plasmodium Triggers the Necrosis of Endothelial Cells Attributed to Malaria Severity"],"prefix":"10.3390","volume":"13","author":[{"given":"Abhishek","family":"Shivappagowdar","sequence":"first","affiliation":[{"name":"Department of Life Science, School of Natural Sciences, Shiv Nadar University, Chithera, Gautam Buddha Nagar, Uttar Pradesh 201314, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swati","family":"Garg","sequence":"additional","affiliation":[{"name":"Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi 110067, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akriti","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Department of Life Science, School of Natural Sciences, Shiv Nadar University, Chithera, Gautam Buddha Nagar, Uttar Pradesh 201314, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3972-6004","authenticated-orcid":false,"given":"Rahul S.","family":"Hada","sequence":"additional","affiliation":[{"name":"Department of Life Science, School of Natural Sciences, Shiv Nadar University, Chithera, Gautam Buddha Nagar, Uttar Pradesh 201314, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inderjeet","family":"Kalia","sequence":"additional","affiliation":[{"name":"Infectious Disease Lab, National Institute of Immunology, New Delhi 110067, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agam P.","family":"Singh","sequence":"additional","affiliation":[{"name":"Infectious Disease Lab, National Institute of Immunology, New Delhi 110067, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lalit C.","family":"Garg","sequence":"additional","affiliation":[{"name":"Gene Regulation Laboratory, National Institute of Immunology, New Delhi 110067, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soumya","family":"Pati","sequence":"additional","affiliation":[{"name":"Department of Life Science, School of Natural Sciences, Shiv Nadar University, Chithera, Gautam Buddha Nagar, Uttar Pradesh 201314, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5286-6605","authenticated-orcid":false,"given":"Shailja","family":"Singh","sequence":"additional","affiliation":[{"name":"Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi 110067, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/(SICI)1096-8628(19971128)73:1<1::AID-AJMG1>3.0.CO;2-Y","article-title":"Retinitis Pigmentosa, Hypopituitarism, Nephronophthisis, and Mild Skeletal Dysplasia (RHYNS): A New Syndrome?","volume":"73","author":"Picco","year":"1997","journal-title":"Am. J. Med. Gen."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.pt.2019.04.010","article-title":"Blood\u2013Brain Barrier in Cerebral Malaria: Pathogenesis and Therapeutic Intervention","volume":"35","author":"Nishanth","year":"2019","journal-title":"Trends Parasitol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1017\/S0031182009991715","article-title":"Cerebral malaria: Why experimental murine models are required to understand the pathogenesis of disease","volume":"137","author":"Hafalla","year":"2010","journal-title":"Parasitology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"389","DOI":"10.4269\/ajtmh.1997.57.389","article-title":"Receptor-specific adhesion and clinical disease in Plasmodium falciparum","volume":"57","author":"Newbold","year":"1997","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1086\/512083","article-title":"Plasmodium falciparum-infected erythrocytes decrease the integrity of human blood-brain barrier endothelial cell monolayers","volume":"195","author":"Tripathi","year":"2007","journal-title":"J. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.ppat.1001021","article-title":"Plasmodium falciparum adhesion on human brain microvascular endothelial cells involves transmigration-like cup formation and induces opening of intercellular junctions","volume":"6","author":"Jambou","year":"2010","journal-title":"PLoS Pathog."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1128\/CVI.00533-16","article-title":"Cytokine profiles in Malawian children presenting with uncomplicated malaria, severe malarial anemia, and cerebral malaria","volume":"24","author":"Mandala","year":"2017","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1203\/PDR.0b013e3181eee738","article-title":"Cerebral malaria: Mechanisms of brain injury and strategies for improved neurocognitive outcome","volume":"68","author":"Idro","year":"2010","journal-title":"Pediatr. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12936-020-03336-z","article-title":"Pathophysiology and neurologic sequelae of cerebral malaria","volume":"19","author":"Schiess","year":"2020","journal-title":"Malar. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12936-016-1342-2","article-title":"Adhesion of Plasmodium falciparum infected erythrocytes in ex vivo perfused placental tissue: A novel model of placental malaria","volume":"15","author":"Pehrson","year":"2016","journal-title":"Malar. J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/S1471-4906(03)00229-1","article-title":"Cytokines: Accelerators and brakes in the pathogenesis of cerebral malaria","volume":"24","author":"Hunt","year":"2003","journal-title":"Trends Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.ijpara.2006.02.004","article-title":"Human cerebral malaria and the blood-brain barrier","volume":"36","author":"Medana","year":"2006","journal-title":"Int. J. Parasitol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1086\/373992","article-title":"Plasmodium falciparum-infected erythrocyte adhesion induces caspase activation and apoptosis in human endothelial cells","volume":"187","author":"Pino","year":"2003","journal-title":"J. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Claser, C., Malleret, B., Gun, S.Y., Wong, A.Y.W., Chang, Z.W., Teo, P., See, P.C.E., Howland, S.W., Ginhoux, F., and R\u00e9nia, L. (2011). Cd8+ T cells and IFN-\u03b3 mediate the time-dependent accumulation of infected red blood cells in deep organs during experimental cerebral malaria. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0018720"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"193","DOI":"10.4161\/viru.19013","article-title":"Cerebral malaria Mysteries at the blood-brain barrier","volume":"3","author":"Howland","year":"2012","journal-title":"Virulence"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e00985-16","DOI":"10.1128\/IAI.00985-16","article-title":"Perforin expression by CD8 T cells is sufficient to cause fatal brain edema during experimental cerebral malaria","volume":"85","author":"Huggins","year":"2017","journal-title":"Infect. Immun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/978-94-017-8881-6_12","article-title":"The role of MACPF proteins in the biology of malaria and other apicomplexan parasites","volume":"80","author":"Tavares","year":"2014","journal-title":"Subcell. Biochem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1097\/MOH.0000000000000334","article-title":"Molecular mechanisms that mediate invasion and egress of malaria parasites from red blood cells","volume":"24","author":"Alaganan","year":"2017","journal-title":"Curr. Opin. Hematol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1111\/cmi.12288","article-title":"Perforin-like protein PPLP2 permeabilizes the red blood cell membrane during egress of Plasmodium falciparum gametocytes","volume":"16","author":"Wirth","year":"2014","journal-title":"Cell. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1111\/cmi.12131","article-title":"A perforin-like protein mediates disruption of the erythrocyte membrane during egress of Plasmodium berghei male gametocytes","volume":"15","author":"Deligianni","year":"2013","journal-title":"Cell. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1038\/ncomms2725","article-title":"Calcium-dependent permeabilization of erythrocytes by a perforin-like protein during egress of malaria parasites","volume":"4","author":"Garg","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"16310","DOI":"10.1073\/pnas.0406187101","article-title":"Essential role of membrane-attack protein in malarial transmission to mosquito host","volume":"101","author":"Kadota","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1111\/j.1462-5822.2004.00447.x","article-title":"A Plasmodium sporozoite protein with a membrane attack complex domain is required for breaching the liver sinusoidal cell layer prior to hepatocyte infection","volume":"7","author":"Ishino","year":"2005","journal-title":"Cell. Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/j.exppara.2007.01.015","article-title":"Plasmodium berghei: Plasmodium perforin-like protein 5 is required for mosquito midgut invasion in Anopheles stephensi","volume":"116","author":"Ecker","year":"2007","journal-title":"Exp. Parasitol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3105","DOI":"10.1016\/j.celrep.2017.03.017","article-title":"Cell Traversal Activity Is Important for Plasmodium falciparum Liver Infection in Humanized Mice","volume":"18","author":"Yang","year":"2017","journal-title":"Cell Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2083","DOI":"10.1007\/s00018-012-1153-8","article-title":"Effects of MACPF\/CDC proteins on lipid membranes","volume":"70","author":"Gilbert","year":"2013","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"121","DOI":"10.3389\/fcimb.2020.00121","article-title":"Plasmodium Perforin-Like Protein Pores on the Host Cell Membrane Contribute in Its Multistage Growth and Erythrocyte Senescence","volume":"10","author":"Garg","year":"2020","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1126\/science.1144706","article-title":"A common fold mediates vertebrate defense and bacterial attack","volume":"317","author":"Rosado","year":"2007","journal-title":"Science"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1007\/s00253-010-2785-y","article-title":"Functional and structural characterization of soluble recombinant epsilon toxin of Clostridium perfringens D, causative agent of enterotoxaemia","volume":"88","author":"Mathur","year":"2010","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6480","DOI":"10.1128\/jb.179.20.6480-6487.1997","article-title":"Clostridium perfringens epsilon-toxin acts on MDCK cells by forming a large membrane complex","volume":"179","author":"Petit","year":"1997","journal-title":"J. Bacteriol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1093\/infdis\/jis746","article-title":"A bacterial RTX toxin causes programmed necrotic cell death through calcium-mediated mitochondrial dysfunction","volume":"207","author":"Kim","year":"2013","journal-title":"J. Infect. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1038\/sj.cdd.4401236","article-title":"Apoptotic and necrotic blebs in epethelial cells display similar neck diameters but different kinase dependency","volume":"10","author":"Barros","year":"2003","journal-title":"Cell Death Differ."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"C817","DOI":"10.1152\/ajpcell.00139.2004","article-title":"Calcium, ATP, and ROS: A mitochondrial love-hate triangle","volume":"287","author":"Brookes","year":"2004","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Ghibelli, L., Cerella, C., and Diederich, M. (2010). The dual role of calcium as messenger and stressor in cell damage, death, and survival. Int. J. Cell Biol., 2010.","DOI":"10.1155\/2010\/546163"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1101\/gad.1376506","article-title":"Necrotic death as a cell fate","volume":"20","author":"Zong","year":"2006","journal-title":"Genes Dev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2977","DOI":"10.1016\/j.bbamcr.2016.09.012","article-title":"Activation of apoptosis signalling pathways by reactive oxygen species","volume":"1863","year":"2016","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Shivappagowdar, A., Pati, S., Narayana, C., Ayana, R., Kaushik, H., Sah, R., Garg, S., Khanna, A., Kumari, J., and Garg, L. (2019). A small bioactive glycoside inhibits epsilon toxin and prevents cell death. DMM Dis. Model. Mech., 12.","DOI":"10.1242\/dmm.040410"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1089\/ars.2010.3356","article-title":"High-mobility group box 1, oxidative stress, and disease","volume":"14","author":"Tang","year":"2011","journal-title":"Antioxid. Redox Signal."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2913","DOI":"10.1084\/jem.20070247","article-title":"HMGB1 release induced by liver ischemia involves Toll-like receptor 4-dependent reactive oxygen species production and calcium-mediated signaling","volume":"204","author":"Tsung","year":"2007","journal-title":"J. Exp. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1002\/dneu.20954","article-title":"Extracellular matrix and matrix receptors in blood-brain barrier formation and stroke","volume":"71","author":"Baeten","year":"2011","journal-title":"Dev. Neurobiol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Tunon-Ortiz, A., and Lamb, T.J. (2019). Blood brain barrier disruption in cerebral malaria: Beyond endothelial cell activation. PLoS Pathog., 15.","DOI":"10.1371\/journal.ppat.1007786"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/B978-0-444-53490-3.00002-9","article-title":"Mechanisms of CNS invasion and damage by parasites","volume":"Volume 114","author":"Kristensson","year":"2013","journal-title":"Handbook of Clinical Neurology"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Kumar Sah, R., Garg, S., Dangi, P., Ponnusamy, K., and Singh, S. (2019). Phosphatidic acid homeostasis regulated by a type-2 phosphatidic acid phosphatase represents a novel druggable target in malaria intervention. Cell Death Discov., 5.","DOI":"10.1038\/s41420-019-0187-1"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1007\/s00018-018-2992-8","article-title":"Mechanisms protecting host cells against bacterial pore-forming toxins","volume":"76","author":"Brito","year":"2019","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/j.bcp.2010.12.027","article-title":"Plasma membrane repair and cellular damage control: The annexin survival kit","volume":"81","author":"Draeger","year":"2011","journal-title":"Biochem. Pharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Chassin, C., Bens, M., De Barry, J., Courjaret, R., Bossu, J.L., Cluzeaud, F., Ben Mkaddem, S., Gibert, M., Poulain, B., and Popoff, M.R. (2007). Pore-forming epsilon toxin causes membrane permeabilization and rapid ATP depletion-mediated cell death in renal collecting duct cells. Am. J. Physiol. Ren. Physiol., 293.","DOI":"10.1152\/ajprenal.00199.2007"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Kennedy, C.L., Smith, D.J., Lyras, D., Chakravorty, A., and Rood, J.I. (2009). Programmed cellular necrosis mediated by the pore-forming \u03b1-toxin from Clostridium septicum. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000516"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.1111\/j.1462-5822.2007.00932.x","article-title":"The multiple mechanisms of Ca2+ signalling by listeriolysin O, the cholesterol-dependent cytolysin of Listeria monocytogenes","volume":"9","author":"Gekara","year":"2007","journal-title":"Cell. Microbiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"18122","DOI":"10.1074\/jbc.273.29.18122","article-title":"Aerolysin induces G-protein activation and Ca2+ release from intracellular stores in human granulocytes","volume":"273","author":"Krause","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.bbabio.2006.04.029","article-title":"Mitochondrial ROS-induced ROS release: An update and review","volume":"1757","author":"Zorov","year":"2006","journal-title":"Biochim. Biophys. Acta Bioenerg."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1038\/nrc1738","article-title":"Lysosomes and autophagy in cell death control","volume":"5","author":"Kroemer","year":"2005","journal-title":"Nat. Rev. Cancer"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Gonz\u00e1lez-Juarbe, N., Gilley, R.P., Hinojosa, C.A., Bradley, K.M., Kamei, A., Gao, G., Dube, P.H., Bergman, M.A., and Orihuela, C.J. (2015). Pore-Forming Toxins Induce Macrophage Necroptosis during Acute Bacterial Pneumonia. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1005337"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"S51","DOI":"10.1016\/S2222-1808(15)60856-8","article-title":"Superoxide dismutase activity in patients of cerebral malaria","volume":"5","author":"Raza","year":"2015","journal-title":"Asian Pac. J. Trop. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"13978","DOI":"10.1073\/pnas.96.24.13978","article-title":"Poly(ADP-ribose) polymerase is a mediator of necrotic cell death by ATP depletion","volume":"96","author":"Ha","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1038\/nature00858","article-title":"Release of chromatin protein HMGB1 by necrotic cells triggers inflammation","volume":"418","author":"Scaffidi","year":"2002","journal-title":"Nature"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"17845","DOI":"10.1074\/jbc.M701465200","article-title":"Activation of poly(ADP)-ribose polymerase (PARP-1) induces release of the pro-inflammatory mediator HMGB1 from the nucleus","volume":"282","author":"Ditsworth","year":"2007","journal-title":"J. Biol. Chem."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/13\/1\/62\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:11:31Z","timestamp":1760159491000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/13\/1\/62"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,15]]},"references-count":56,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,1]]}},"alternative-id":["toxins13010062"],"URL":"https:\/\/doi.org\/10.3390\/toxins13010062","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,15]]}}}