Ras activation modulates methylglyoxal-induced mesangial cell apoptosis through superoxide production

Wei Jan Huang, Chun Wu Tung, Cheng Ho, Jen Tsung Yang, Min Li Chen, Pey Jium Chang, Pei Hsien Lee, Chun Liang Lin, Jeng Yi Wang

研究成果: 雜誌貢獻文章同行評審

18 引文 斯高帕斯(Scopus)

摘要

Aims. While previous studies have demonstrated that diabetic nephropathy is attributable to glucose-derived dicarbonyl compounds, methylglyoxal (MGO)-inducing apoptosis in renal mesangial cells, the molecular mechanism of upper stream redox signaling modulation, has not been fully elucidated. Methods: Rat mesangial cells pretreated with or without superoxide dismutase, diphenyloniodium, SB203580, and manumycin A were cultured in methylglyoxal stress-induced apoptosis. Signaling protein expression, flow cytometry, and morphological features of apoptotic cell death were assessed. Results: Methylglyoxal decreased cell viability in mesangial cells. Superoxide mediated methylglyoxal-induced caspase 3 cleavage. Pretreatment with diphenyloniodium, SB203580, and manumycin A reduced methylglyoxal augmentation of superoxide synthesis and caspase-3 activation. Methylglyoxal rapidly enhanced Ras activation and progressively increased cytosolic P38 and nuclear c-Jun activation. Scavenging of superoxide by superoxide dismutase or diphenyloniodium, inhibiting P38 by SB203580, and inhibiting Ras with manumycin A successfully reduced the promoting effect of methylglyoxal on P38 and c-Jun phosphorylation (activation). Furthermore, pretreatment with superoxide dismutase, diphenyloniodium, SB203580, and manumycin A significantly attenuated methylglyoxal induction of apoptosis on the basis of Annexin-V assay and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labelling (TUNEL) staining. Conclusions. This study has shown that methylglyoxal increased Ras modulation of superoxide-mediated P38 activation and c-Jun activation, which resulted in increased apoptosis.

原文英語
頁(從 - 到)911-921
頁數11
期刊Renal Failure
29
發行號7
DOIs
出版狀態已發佈 - 九月 2007
對外發佈

ASJC Scopus subject areas

  • 腎臟病學

指紋

深入研究「Ras activation modulates methylglyoxal-induced mesangial cell apoptosis through superoxide production」主題。共同形成了獨特的指紋。

引用此