Nec-1 Protects against Nonapoptotic Cell Death in Cisplatin-Induced Kidney Injury

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dc.contributor.authorTristao, Vivian Regina [UNIFESP]
dc.contributor.authorGoncalves, Paula Fernanda [UNIFESP]
dc.contributor.authorDalboni, Maria Aparecida [UNIFESP]
dc.contributor.authorBatista, Marcelo Costa [UNIFESP]
dc.contributor.authorDurao, Marcelino de Souza [UNIFESP]
dc.contributor.authorMartins Monte, Julio Cesar [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T14:17:47Z
dc.date.available2016-01-24T14:17:47Z
dc.date.issued2012-01-01
dc.description.abstractBackground/aims: Necrostatin-1 (Nec-1) inhibits necroptosis, a nonapoptotic cell death pathway. Acute kidney injury (AKI) is a clinical problem of high incidence and mortality. It involves several mechanisms of cell death. We aim to evaluate the effect of Nec-1 in the toxic kidney injury model by cisplatin. Methods: We analyzed the effect of Nec-1 in AKI by cisplatin in human proximal tubule cells by flow cytometry. Results: Our results show that Nec-1 has no effect on apoptosis in renal tubular epithelial cells (Nec-1 + Cis group 13.4 +/- 1.7% vs. Cis group 14.6 +/- 1.4%) (p > 0.05). But, in conditions in which apoptosis was blocked by benzyloxy-carbonyl-Val-Ala-Asp-fluoromethyl ketone (z-VAD-fmk) the use of Nec-1 completely reversed cell viability (Nec-1 + Cis + z-VAD group 72.9 +/- 6.3% vs. Cis group 35.5 +/- 2.2%) (p < 0.05) suggesting that Nec-1 has effect on nonapoptotic cell death (necroptosis). Conclusion: Our findings suggest that the combined use of apoptosis and necroptosis inhibitors can provide additional cytoprotection in AKI. Furthermore, this is the first study to demonstrate that Nec-1 inhibits tubular kidney cell death and restores cell viability via a nonapoptotic mechanism.en
dc.description.affiliationUniversidade Federal de São Paulo, Dept Med, São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Med, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipIDFAPESP: 08/09773-4
dc.format.extent373-377
dc.identifierhttp://dx.doi.org/10.3109/0886022X.2011.647343
dc.identifier.citationRenal Failure. London: Informa Healthcare, v. 34, n. 3, p. 373-377, 2012.
dc.identifier.doi10.3109/0886022X.2011.647343
dc.identifier.issn0886-022X
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/34510
dc.identifier.wosWOS:000300558700019
dc.language.isoeng
dc.publisherInforma Healthcare
dc.relation.ispartofRenal Failure
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.rights.licensehttp://informahealthcare.com/userimages/ContentEditor/1255620309227/Copyright_And_Permissions.pdf
dc.subjectnecrostatin-1en
dc.subjectcytoprotectionen
dc.subjectnecroptosisen
dc.subjectcisplatinen
dc.subjectacute kidney injuryen
dc.titleNec-1 Protects against Nonapoptotic Cell Death in Cisplatin-Induced Kidney Injuryen
dc.typeinfo:eu-repo/semantics/article
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