TY - JOUR
T1 - Resveratrol ameliorates high glucose-induced protein synthesis in glomerular epithelial cells
AU - Lee, Myung Ja
AU - Feliers, Denis
AU - Sataranatarajan, Kavithalakshmi
AU - Mariappan, Meenalakshmi M.
AU - Li, Manli
AU - Barnes, Jeffrey L.
AU - Choudhury, Goutam Ghosh
AU - Kasinath, Balakuntalam S.
N1 - Funding Information:
This study was supported by the NIH (grants DK077295 to BSK, DK050190 to GGC), NIDDK O'Brien Kidney Center Grant (BSK, DF), Veterans Research Service (BSK, GGC), American Diabetes Association (grant 7-05-RA-60 to BSK), Juvenile Diabetes Research Foundation (grant 3-2007-245 to MMM/BSK, grant 1-2008-185 to GGC), and, American Heart Association (grant SDG 0630283N to DF). GGC is a recipient of VA Research Career Scientist Award. We thank Dr. Nicolas Musi and Dr. Koh for helpful suggestions on LKB1 activity assay.
PY - 2010/1
Y1 - 2010/1
N2 - 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 that 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.
AB - 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 that 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.
KW - AMP-activated protein kinase
KW - Diabetic nephropathy
KW - LKB1
KW - Protein synthesis
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U2 - 10.1016/j.cellsig.2009.09.011
DO - 10.1016/j.cellsig.2009.09.011
M3 - Article
C2 - 19765649
AN - SCOPUS:70350043289
SN - 0898-6568
VL - 22
SP - 65
EP - 70
JO - Cellular Signalling
JF - Cellular Signalling
IS - 1
ER -