Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/71208
Type: Artigo de periódico
Title: Role of caspases on cell death, inflammation, and cell cycle in glycerol-induced acute renal failure
Author: Homsi, E
Janino, P
de Faria, JBL
Abstract: Caspases are the main executioners of apoptosis as well as interleukin (IL)-1 beta and IL-18 conversion to active forms. They are activated after acute kidney injuries. In this study, we evaluated the importance of the caspase family in the pathogenesis and recovery of glycerol-induced acute renal failure in rats (Gly-ARF). Rats were treated with pan-caspase or selective caspase 1 and 3 inhibitors at the moment we injected glycerol. Renal function, renal histology ( HE), transferase- mediated deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling staining for apoptosis, leukocytes infiltration ( immunohistochemistry), renal expression of IL-1 beta and IL-18 ( immunohistochemistry and Western blot), tubular regeneration ( 5-bromo-2'-deoxyuridine ( BrdU) incorporation), and P27(Kip) expression ( Western blot) were evaluated at appropriate times. All inhibitors reduced the renal function impairment. Pan-caspase and caspase-3 inhibitors reduced cellular death ( necrosis and apoptosis) 24 h after Gly-ARF. All caspases inhibitors reduced macrophages infiltration. The expression of total IL-1 beta was enhanced in Gly-ARF, but the active IL-1 beta and IL-18 forms were abolished in pan-caspase treated rats. Caspase-1 inhibitor attenuated Gly-ARF but not tubular injury suggesting glomerular hemodynamic improvement. There was striking regenerative response 48 h after Gly-ARF characterized by enhanced BrdU incorporation and reduced expression of p27(Kip.) This response was not blunted by caspases inhibition. Our findings demonstrate that caspases participate in important pathogenic mechanisms in Gly-ARF such as inflammation, apoptosis, vasoconstriction, and tubular necrosis. The early inhibition of caspases attenuates these mechanisms and reduces the renal function impairment in Gly-ARF.
Subject: acute renal failure
apoptosis
inflammation
caspases
Country: EUA
Editor: Nature Publishing Group
Rights: fechado
Identifier DOI: 10.1038/sj.ki.5000315
Date Issue: 2006
Appears in Collections:Artigos e Materiais de Revistas Científicas - Unicamp

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