title: Resveratrol ameliorates high glucose-induced protein synthesis in glomerular epithelial cells.
abstract: 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.
authors.affiliation: O'Brien Kidney Research Center, Division of Nephrology, Department of Medicine, University of Texas Health Science Center, GRECC, South Texas Veterans Health Care System, San Antonio, TX 78229-3900, USA.
authors.forename: Myung-Ja
authors.initials: MJ
authors.lastname: Lee
authors.forename: Denis
authors.initials: D
authors.lastname: Feliers
authors.forename: Kavithalakshmi
authors.initials: K
authors.lastname: Sataranatarajan
authors.forename: Meenalakshmi M
authors.initials: MM
authors.lastname: Mariappan
authors.forename: Manli
authors.initials: M
authors.lastname: Li
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Barnes
authors.forename: Goutam Ghosh
authors.initials: GG
authors.lastname: Choudhury
authors.forename: Balakuntalam S
authors.initials: BS
authors.lastname: Kasinath
mesh_terms: D000818:Animals; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D014176:Protein Biosynthesis / Q000187:drug effects*; D011506:Proteins / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D011506:Proteins; D013267:Stilbenes; D005947:Glucose; D000077185:Resveratrol