| Full text | |
| Author(s): |
Tristao, Vivian Regina
[1]
;
Pessoa, Edson A.
[1]
;
Nakamichi, Renata
[1]
;
Reis, Luciana A.
[1]
;
Batista, Marcelo Costa
[1]
;
Durao Junior, Marcelino de Souza
[1]
;
Martins Monte, Julio Cesar
[1]
Total Authors: 7
|
| Affiliation: | [1] Univ Fed Sao Paulo, Sao Paulo - Brazil
Total Affiliations: 1
|
| Document type: | Journal article |
| Source: | Apoptosis; v. 21, n. 1, p. 51-59, JAN 2016. |
| Web of Science Citations: | 14 |
| Abstract | |
Necroptosis is a nonapoptotic cell death pathway. We aim to study the effect of necrostatin-1 (a specific necroptosis inhibitor) in cisplatin-induced injury. We analyzed the effect of the combined use of inhibitors of apoptosis (z-vad) and necroptosis (necrostatin-1) in acute kidney injury by cisplatin in human proximal tubule cells. Our results showed moderate effectiveness in cytoprotection after treatment with z-vad. But the concomitant use of inhibitors (z-vad and necrostatin-1) presented synergistic and additive protection. The present study analyzed the caspase-3 activity and we observed a significant decrease in the group treated with z-vad and cisplatin. However we did not observe changes in the group treated with both inhibitors (z-vad and necrostatin-1) and cisplatin. Thus, demonstrating that necroptosis is a caspase-independent mechanism. We also analyzed the effect of necrostatin-1 in vivo model. C57BL/6 mice were treated with cisplatin and/or inhibitors. The concomitant use of inhibitors (z-vad and necrostatin-1) recovered renal function and decreased levels of urinary Ngal. Additionally, we analyzed the expression of RIP-1, a specific marker for necroptosis. In animals treated with cisplatin and z-VAD levels of RIP-1 were higher. This result reinforces that necroptosis occurs only in conditions where apoptosis was blocked. However, the use of both inhibitors (z-vad and necrostatin-1) provided additional protection. In conclusion, our study has a significant potential to show in vitro and in vivo protection obtained by necrostatin-1. Therefore, our results suggest that necroptosis may be an important mechanism of cell death after kidney injury. (AU) | |
| FAPESP's process: | 08/09773-4 - The contribution of necroptosis and apoptosis during acute kidney injury |
| Grantee: | Júlio César Martins Monte |
| Support type: | Regular Research Grants |