{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T21:41:30Z","timestamp":1775943690544,"version":"3.50.1"},"reference-count":65,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2018,7,10]],"date-time":"2018-07-10T00:00:00Z","timestamp":1531180800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Hydrogen sulfide (H2S) is an endogenous gasotransmitter recognized as an essential body product with a dual, biphasic action. It can function as an antioxidant and a cytoprotective, but also as a poison with a high probability of causing brain damage when present at noxious levels. In a previous study, we measured toxic liquoral levels of H2S in sporadic amyotrophic lateral sclerosis (ALS) patients and in the familial ALS (fALS) mouse model, SOD1G93A. In addition, we experimentally demonstrated that H2S is extremely and selectively toxic to motor neurons, and that it is released by glial cells and increases Ca2+ concentration in motor neurons due to a lack of ATP. The presented study further examines the effect of toxic concentrations of H2S on embryonic mouse spinal-cord cultures. We performed a proteomic analysis that revealed a significant H2S-mediated activation of pathways related to oxidative stress and cell death, particularly the Nrf-2-mediated oxidative stress response and peroxiredoxins. Furthermore, we report that Na2S (a stable precursor of H2S) toxicity is, at least in part, reverted by the Bax inhibitor V5 and by necrostatin, a potent necroptosis inhibitor.<\/jats:p>","DOI":"10.3390\/antiox7070087","type":"journal-article","created":{"date-parts":[[2018,7,10]],"date-time":"2018-07-10T09:24:01Z","timestamp":1531214641000},"page":"87","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Proteomics and Toxicity Analysis of Spinal-Cord Primary Cultures upon Hydrogen Sulfide Treatment"],"prefix":"10.3390","volume":"7","author":[{"given":"Viviana","family":"Greco","sequence":"first","affiliation":[{"name":"Institute of Biochemistry and Clinical Biochemistry, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Department of Laboratory Diagnostic and Infectious Diseases, Fondazione Policlinico Universitario Agostino Gemelli-IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alida","family":"Spalloni","sequence":"additional","affiliation":[{"name":"Department of Experimental Neuroscience, Molecular Neurobiology Unit, Fondazione Santa Lucia, 00143 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor","family":"Corasolla Carregari","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Clinical Biochemistry, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Department of Laboratory Diagnostic and Infectious Diseases, Fondazione Policlinico Universitario Agostino Gemelli-IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7141-1817","authenticated-orcid":false,"given":"Luisa","family":"Pieroni","sequence":"additional","affiliation":[{"name":"Department of Experimental Neuroscience, Proteomics and Metabonomics Unit, Fondazione Santa Lucia-IRCCS, 00143 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Persichilli","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Clinical Biochemistry, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Department of Laboratory Diagnostic and Infectious Diseases, Fondazione Policlinico Universitario Agostino Gemelli-IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola B.","family":"Mercuri","sequence":"additional","affiliation":[{"name":"Department of Systems Medicine, Policlinico Universitario \u201cTor Vergata\u201d, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"},{"name":"Department of Experimental Neuroscience, Experimental Neurology Unit, 00143 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Urbani","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Clinical Biochemistry, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Department of Laboratory Diagnostic and Infectious Diseases, Fondazione Policlinico Universitario Agostino Gemelli-IRCCS, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrizia","family":"Longone","sequence":"additional","affiliation":[{"name":"Department of Experimental Neuroscience, Molecular Neurobiology Unit, Fondazione Santa Lucia, 00143 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,7,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1002\/ana.24372","article-title":"Evidence of hydrogen sulfide involvement in amyotrophic lateral sclerosis","volume":"77","author":"Davoli","year":"2015","journal-title":"Ann. Neurol."},{"key":"ref_2","first-page":"re2","article-title":"Signaling by gasotransmitters","volume":"28","author":"Mustafa","year":"2009","journal-title":"Sci. Signal."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"59ps54","DOI":"10.1126\/scitranslmed.3000721","article-title":"Gastransmitters: New frontiers for translational science","volume":"2","author":"Szabo","year":"2010","journal-title":"Sci. Transl. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.bcp.2017.11.019","article-title":"Gasotransmitter hydrogen sulfide signaling in neuronal health and disease","volume":"149","author":"Paul","year":"2018","journal-title":"Biochem. Pharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1089\/ars.2014.5869","article-title":"Signaling molecules: Hydrogen sulfide and polysulfide","volume":"22","author":"Kimura","year":"2015","journal-title":"Antioxid. Redox Signal."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1111\/j.1474-9726.2009.00543.x","article-title":"Neuroprotective effects of hydrogen sulfide on Parkinson\u2019s disease rat models","volume":"9","author":"Hu","year":"2010","journal-title":"Aging Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.neuroscience.2016.03.053","article-title":"Hydrogen sulfide prevents Abeta-induced neuronal apoptosis by attenuating mitochondrial translocation of PTEN","volume":"325","author":"Cui","year":"2016","journal-title":"Neuroscience"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1016\/j.pharep.2016.05.006","article-title":"Hydrogen sulfide down-regulates BACE1 and PS1 via activating PI3K\/Akt pathway in the brain of APP\/PS1 transgenic mouse","volume":"68","author":"He","year":"2016","journal-title":"Pharmacol. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.forsciint.2006.02.043","article-title":"Fatal occupational inhalation of hydrogen sulfide","volume":"169","author":"Bartoli","year":"2007","journal-title":"Forensic Sci. Int."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.forsciint.2010.09.008","article-title":"Toxicological analysis of 17 autopsy cases of hydrogen sulfide poisoning resulting from the inhalation of intentionally generated hydrogen sulfide gas","volume":"207","author":"Maebashi","year":"2011","journal-title":"Forensic Sci. Int."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.bbrc.2011.09.144","article-title":"Involvement of ERK in NMDA receptor-independent cortical neurotoxicity of hydrogen sulfide","volume":"414","author":"Kurokawa","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.neuropharm.2007.06.014","article-title":"Hydrogen sulfide induced neuronal death occurs via glutamate receptor and is associated with calpain activation and lysosomal rupture in mouse primary cortical neurons","volume":"53","author":"Cheung","year":"2007","journal-title":"Neuropharmacology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.nbd.2003.11.012","article-title":"Cu\/Zn-superoxide dismutase (GLY93\u2192ALA) mutation alters AMPA receptor subunit expression and function and potentiates kainate-mediated toxicity in motor neurons in culture","volume":"2","author":"Spalloni","year":"2004","journal-title":"Neurobiol. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.jprot.2015.05.040","article-title":"Mechanisms of antibiotic resistance to enrofloxacin in uropathogenic Escherichia coli in dog","volume":"127","author":"Piras","year":"2015","journal-title":"J. Proteom."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1039\/C6MB00723F","article-title":"Changes in protein expression profiles in bovine endometrial epithelial cells exposed to E. coli LPS challenge","volume":"13","author":"Piras","year":"2017","journal-title":"Mol. Biosyst."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1074\/mcp.M500230-MCP200","article-title":"Absolute quantification of proteins by LCMSE a virtue of parallel MS acquisition","volume":"5","author":"Silva","year":"2006","journal-title":"Mol. Cell. Proteom."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1074\/mcp.M600303-MCP200","article-title":"Analysis and quantification of diagnostic serum markers and protein signatures for Gaucher disease","volume":"6","author":"Vissers","year":"2007","journal-title":"Mol. Cell. Proteom."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1096\/fj.04-1815fje","article-title":"Hydrogen sulfide protects neurons from oxidative stress","volume":"18","author":"Kimura","year":"2004","journal-title":"FASEB J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1096\/fj.03-1052fje","article-title":"Hydrogen sulfide induces calcium waves in astrocytes","volume":"18","author":"Nagai","year":"2004","journal-title":"FASEB J."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Marutani, E., Yamada, M., Ida, T., Tokuda, K., Ikeda, K., Kai, S., Shirozu, K., Hayashida, K., Kosugi, S., and Hanaoka, K. (2015). Thiosulfate Mediates Cytoprotective Effects of Hydrogen Sulfide Against Neuronal Ischemia. J. Am. Heart Assoc., 4.","DOI":"10.1161\/JAHA.115.002125"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1002\/glia.1061","article-title":"Inducible ablation of astrocytes shows that these cells are required for neuronal survival in the adult brain","volume":"34","author":"Cui","year":"2001","journal-title":"Glia"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1038\/s41419-017-0153-x","article-title":"Functional and structural damage of neurons by innate immune mechanisms during neurodegeneration","volume":"25","author":"Ising","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1038\/nn1876","article-title":"Astrocytes expressing ALS-linked mutated SOD1 release factors selectively toxic to motor neurons","volume":"10","author":"Nagai","year":"2007","journal-title":"Nat. Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"42","DOI":"10.2174\/18715273113126660189","article-title":"Necroptosis: Who knew there were so many interesting ways to die?","volume":"13","author":"Fayaz","year":"2014","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1016\/j.neuron.2014.01.011","article-title":"Necroptosis drives motor neuron death in models of both sporadic and familial ALS","volume":"81","author":"Re","year":"2014","journal-title":"Neuron"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1126\/science.aaf6803","article-title":"RIPK1 mediates axonal degeneration by promoting inflammation and necroptosis in ALS","volume":"353","author":"Ito","year":"2016","journal-title":"Science"},{"key":"ref_27","first-page":"379","article-title":"Antibody to caspase-cleaved actin detects apoptosis in differentiated neuroblastoma and plaque-associated neurons and microglia in Alzheimer\u2019s diseases","volume":"152","author":"Yang","year":"1998","journal-title":"Am. J. Pathol."},{"key":"ref_28","first-page":"619","article-title":"Fractin immunostaining for the detection of apoptotic cells and apoptotic bodies in Formalin-fixed and paraffin-embedded tissues","volume":"79","author":"Suurmeijer","year":"1999","journal-title":"Lab. Investig."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/S0092-8674(00)80434-1","article-title":"Cytochrome c and dATP-dependent formation of Apaf-1\/caspase-9 complex initiates an apoptotic protease cascade","volume":"91","author":"Li","year":"1997","journal-title":"Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/S0092-8674(00)80501-2","article-title":"Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3","volume":"90","author":"Zou","year":"1997","journal-title":"Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4997","DOI":"10.1073\/pnas.95.9.4997","article-title":"Bax directly induces release of cytochrome c from isolated mitochondria","volume":"95","author":"Jurgensmeier","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1016\/j.cell.2008.11.010","article-title":"Membrane binding by tBid initiates an ordered series of events culminating in membrane permeabilization by Bax","volume":"135","author":"Lovell","year":"2008","journal-title":"Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1016\/j.cell.2008.11.029","article-title":"Bcl-2 proteins and apoptosis: Choose your partner","volume":"35","author":"Shore","year":"2008","journal-title":"Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1126\/science.1115035","article-title":"Caspases 3 and 7: Key mediators of mitochondrial events of apoptosis","volume":"311","author":"Lakhani","year":"2006","journal-title":"Science"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1146\/annurev-pathol-052016-100247","article-title":"Necroptosis: Mechanisms and Relevance to Disease","volume":"12","author":"Galluzzi","year":"2017","journal-title":"Annu. Rev. Pathol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3745","DOI":"10.1128\/MCB.05303-11","article-title":"Requirement of FADD, NEMO, and BAX\/BAK for aberrant mitochondrial function in tumor necrosis factor alpha-induced necrosis","volume":"18","author":"Irrinki","year":"2011","journal-title":"Mol. Cell. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Karch, J., Kanisicak, O., Brody, M.J., Sargent, M.A., Michael, D.M., and Molkentin, J.D. (2015). Necroptosis Interfaces with MOMP and the MPTP in Mediating Cell Death. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0130520"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/cdd.2016.102","article-title":"Bak-dependent mitochondrial amplification step contributes to Smac mimetic\/glucocorticoid-induced necroptosis","volume":"24","author":"Rohde","year":"2017","journal-title":"Cell Death Differ."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1016\/j.celrep.2013.10.034","article-title":"Widespread mitochondrial depletion via mitophagy does not compromise necroptosis","volume":"5","author":"Tait","year":"2013","journal-title":"Cell Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"12024","DOI":"10.1073\/pnas.1305538110","article-title":"Two independent pathways of regulated necrosis mediate ischemia-reperfusion injury","volume":"110","author":"Linkermann","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1196\/annals.1427.036","article-title":"The Nrf2-ARE pathway: An indicator and modulator of oxidative stress in neurodegeneration","volume":"1147","author":"Johnson","year":"2008","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"22925","DOI":"10.1074\/jbc.M414635200","article-title":"Induction of the Nrf2-driven antioxidant response confers neuroprotection during mitochondrial stress in vivo","volume":"280","author":"Shih","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.mam.2011.10.006","article-title":"Oxidative stress in health and disease: The therapeutic potential of Nrf2 activation","volume":"32","author":"Hybertson","year":"2011","journal-title":"Mol. Asp. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1073\/pnas.0408487101","article-title":"Protection from mitochondrial complex II inhibition in vitro and in vivo by Nrf2-mediated transcription","volume":"102","author":"Calkins","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Innamorato, N.G., Jazwa, A., Rojo, A.I., Garc\u00eda, C., Fern\u00e1ndez-Ruiz, J., Grochot-Przeczek, A., Stachurska, A., Jozkowicz, A., Dulak, J., and Cuadrado, A. (2010). Different susceptibility to the Parkinson\u2019s toxin MPTP in mice lacking the redox master regulator Nrf2 or its target gene heme oxygenase-1. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0011838"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"13574","DOI":"10.1523\/JNEUROSCI.4099-08.2008","article-title":"Nrf2 activation in astrocytes protects against neurodegeneration in mouse models of familial amyotrophic lateral sclerosis","volume":"28","author":"Vargas","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Vargas, M.R., Burton, N.C., Kutzke, J., Gan, L., Johnson, D.A., Sch\u00e4fer, M., Werner, S., and Johnson, J.A. (2013). Absence of Nrf2 or its selective overexpression in neurons and muscle does not affect survival in ALS-linked mutant hSOD1 mouse models. PLoS ONE, 8.","DOI":"10.1371\/annotation\/28f68b10-e23d-4519-8d52-8cc94fe372b1"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1002\/ana.410380424","article-title":"Oxidative damage to protein in sporadic motor neuron disease spinal cord","volume":"38","author":"Shaw","year":"1995","journal-title":"Ann. Neurol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1002\/ana.410440419","article-title":"Presence of 4-hydroxynonenal in cerebrospinal fluid of patients with sporadic amyotrophic lateral sclerosis","volume":"44","author":"Smith","year":"1998","journal-title":"Ann. Neurol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s004019900173","article-title":"Nonoxidative protein glycation is implicated in familial amyotrophic lateral sclerosis with superoxide dismutase-1 mutation","volume":"100","author":"Shibata","year":"2000","journal-title":"Acta Neuropathol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/S0006-8993(01)02926-2","article-title":"Morphological evidence for lipid peroxidation and protein glycoxidation in spinal cords from sporadic amyotrophic lateral sclerosis patients","volume":"917","author":"Shibata","year":"2001","journal-title":"Brain Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.expneurol.2007.05.026","article-title":"Activation of the Nrf2-ARE pathway in muscle and spinal cord during ALS-like pathology in mice expressing mutant SOD1","volume":"207","author":"Kraft","year":"2007","journal-title":"Exp. Neurol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.tibs.2015.05.001","article-title":"Peroxiredoxins: Guardians against oxidative stress and modulators of peroxide signaling","volume":"40","author":"Perkins","year":"2015","journal-title":"Trends Biochem. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"60","DOI":"10.14348\/molcells.2016.2341","article-title":"Multiple Roles of Peroxiredoxins in Inflammation","volume":"39","author":"Knoops","year":"2016","journal-title":"Mol. Cells"},{"key":"ref_55","first-page":"729","article-title":"Histological recovery of the hepatocytes is based on the redox system upregulation in the animal models of mutant superoxide dismutase (SOD)1-linked amyotrophic lateral sclerosis","volume":"21","author":"Kato","year":"2006","journal-title":"Histol. Histopathol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1096\/fj.01-0944rev","article-title":"Cellular adaptation to hypoxia: O2-sensing protein hydroxylases, hypoxia-inducible transcription factors, and O2-regulated gene expression","volume":"16","author":"Wenger","year":"2002","journal-title":"FASEB J."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"5510","DOI":"10.1073\/pnas.92.12.5510","article-title":"Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension","volume":"92","author":"Wang","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1002\/jcb.24438","article-title":"HIFs, angiogenesis, and cancer","volume":"114","author":"Yang","year":"2013","journal-title":"J. Cell. Biochem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1038\/nm0906-996","article-title":"Hypoxia pathway linked to kidney failure","volume":"12","author":"Semenza","year":"2006","journal-title":"Nat. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1111\/j.1476-5381.2011.01208.x","article-title":"Role of hypoxia-inducible factors in the dexrazoxane-mediated protection of cardiomyocytes from doxorubicin-induced toxicity","volume":"163","author":"Spagnuolo","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.tibs.2008.08.002","article-title":"HIF-1 regulation: Not so easy come, easy go","volume":"33","author":"Powis","year":"2008","journal-title":"Trends Biochem. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.abb.2016.09.018","article-title":"Biological chemistry of hydrogen sulfide and persulfides","volume":"617","author":"Cuevasanta","year":"2017","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"758678","DOI":"10.1155\/2015\/758678","article-title":"Interaction of Hydrogen Sulfide with Oxygen Sensing under Hypoxia","volume":"2015","author":"Wu","year":"2015","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1248\/bpb.33.1550","article-title":"Hypoxia-inducible factor-1\u03b1 is involved in the pro-angiogenic effect of hydrogen sulfide under hypoxic stress","volume":"33","author":"Liu","year":"2010","journal-title":"Biol. Pharm. Bull."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1089\/ars.2011.3882","article-title":"Hydrogen sulfide inhibits hypoxia- but not anoxia-induced hypoxia-inducible factor 1 activation in a von hippel-lindau- and mitochondria-dependent manner","volume":"16","author":"Kai","year":"2012","journal-title":"Antioxid. Redox Signal."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/7\/7\/87\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:11:27Z","timestamp":1760195487000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/7\/7\/87"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7,10]]},"references-count":65,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2018,7]]}},"alternative-id":["antiox7070087"],"URL":"https:\/\/doi.org\/10.3390\/antiox7070087","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,7,10]]}}}