Resveratrol ameliorates high glucose-induced protein synthesis in glomerular epithelial cells.

Resveratrol ameliorates high glucose-induced protein synthesis in glomerular epithelial cells.
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DOI:
10.1016/j.cellsig.2009.09.011
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发表时间:
2010-01
影响因子:
4.8
通讯作者:
Kasinath BS
Kasinath BS
中科院分区:
生物学2区
文献类型:
--
作者:
Lee MJ;Feliers D;Sataranatarajan K;Mariappan MM;Li M;Barnes JL;Choudhury GG;Kasinath BS

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High glucose-induced protein synthesis in the glomerular epithelial cell (GEC) is partly dependent on reduction in phosphorylation of AMP-activated protein kinase (AMPK). We evaluated the effect of resveratrol, a phytophenol known to stimulate AMPK, on protein synthesis. Resveratrol completely inhibited high glucose stimulation of protein synthesis and synthesis of fibronectin, an important matrix protein, at 3 days. Resveratrol dose-dependently increased AMPK phosphorylation and abolished high glucose-induced reduction in its phosphorylation. We examined the effect of resveratrol on critical steps in mRNA translation, a critical event in protein synthesis. Resveratrol inhibited high glucose-induced changes in association of eIF4E with eIF4G, phosphorylation of eIF4E, eEF2, eEF2 kinase and, p70S6 kinase, indicating it affects important events in both initiation and elongation phases of mRNA translation. Upstream regulators of AMPK in high glucose-treated GEC were explored. High glucose augmented acetylation of LKB1, the upstream kinase for AMPK, and inhibited its activity. Resveratrol prevented acetylation of LKB1 and restored its activity in high glucose-treated cells; this action did not appear to depend on SIRT1, a class III histone deacetylase. Our data show that resveratrol ameliorates protein synthesis by regulating the LKB1-AMPK axis.
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