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

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

Autor Tristao, Vivian Regina Autor UNIFESP Google Scholar
Goncalves, Paula Fernanda Autor UNIFESP Google Scholar
Dalboni, Maria Aparecida Autor UNIFESP Google Scholar
Batista, Marcelo Costa Autor UNIFESP Google Scholar
Durao, Marcelino de Souza Autor UNIFESP Google Scholar
Martins Monte, Julio Cesar Autor UNIFESP Google Scholar
Instituição Universidade Federal de São Paulo (UNIFESP)
Resumo Background/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.
Assunto necrostatin-1
cytoprotection
necroptosis
cisplatin
acute kidney injury
Idioma Inglês
Financiador Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Número do financiamento FAPESP: 08/09773-4
Data 2012-01-01
Publicado em Renal Failure. London: Informa Healthcare, v. 34, n. 3, p. 373-377, 2012.
ISSN 0886-022X (Sherpa/Romeo, fator de impacto)
Editor Informa Healthcare
Extensão 373-377
Fonte http://dx.doi.org/10.3109/0886022X.2011.647343
Direito de acesso Acesso restrito
Tipo Artigo
Web of Science WOS:000300558700019
URI http://repositorio.unifesp.br/handle/11600/34510

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