Hydrogen Sulfide Inhibits High Glucose-induced Matrix Protein Synthesis by Activating AMP-activated Protein Kinase in Renal Epithelial Cells

• DOI: 10.1074/jbc.m111.278325
• Publication Date: 2011-12-10T04:11:48Z
• Authors: Hak Joo Lee; Meenalakshmi M. M...; Denis Feliers; Rita C. Cavaglieri; Kavithalakshmi Sa...; Hanna E. Abboud; Goutam Ghosh Chou...; Balakuntalam S. K...
• Keywords: AMP-Activated Protein Kinase

Hydrogen sulfide, a signaling gas, affects several cell functions. We hypothesized that hydrogen sulfide modulates high glucose (30 mm) stimulation of matrix protein synthesis in glomerular epithelial cells. High global synthesis, cellular hypertrophy, and laminin type IV collagen content was inhibited by sodium hydrosulfide (NaHS), an H(2)S donor. activation mammalian target rapamycin (mTOR) complex 1 (mTORC1), shown phosphorylation p70S6 kinase 4E-BP1, NaHS. stimulated mTORC1 to promote key events the initiation elongation phases mRNA translation: binding eIF4A eIF4G, reduction PDCD4 expression inhibition its eIF4A, eEF2 phosphorylation, dephosphorylation eEF2; these were The role AMP-activated (AMPK), inhibitor examined. NaHS dose-dependently AMPK restored reduced glucose. Compound C, inhibitor, abolished modulation effect on translation as well synthesis. induction siRNA for calmodulin β, but not LKB1, upstream kinases AMPK; STO-609, β had same effect. Renal cortical cystathionine β-synthase γ-lyase, sulfide-generating enzymes, significantly mice with diabetes or 2 diabetes, coinciding renal hypertrophy accumulation. is newly identified modulator kidney, generation may contribute kidney injury diabetes.