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

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

Author 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
Institution Universidade Federal de São Paulo (UNIFESP)
Abstract 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.
Keywords necrostatin-1
cytoprotection
necroptosis
cisplatin
acute kidney injury
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Grant number FAPESP: 08/09773-4
Date 2012-01-01
Published in Renal Failure. London: Informa Healthcare, v. 34, n. 3, p. 373-377, 2012.
ISSN 0886-022X (Sherpa/Romeo, impact factor)
Publisher Informa Healthcare
Extent 373-377
Origin http://dx.doi.org/10.3109/0886022X.2011.647343
Access rights Closed access
Type Article
Web of Science ID WOS:000300558700019
URI http://repositorio.unifesp.br/handle/11600/34510

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