Alpha lipoic acid modulates high glucose-induced rat mesangial cell proliferation via mTOR signaling pathway / 中华内分泌代谢杂志

ABSTRACT

Objective To examine whether alpha lipoic acid (LA) regulates high glucose-induced mesangial cell proliferation via mammalian target of rapamycin (mTOR) signaling.Methods The cell proliferation and cycle were determined by methylthiazoletetrazolium(MTT) assay and flow cytometry,respectively.The mRNA expression of AMP-activated protein kinase(AMPK) was detected by realtime PCR.The phosphorylation levels of protein kinase B (Akt),mTOR,eukaryotic translation initiation factor 4E binding protein 1 (4EBP1),and 70S6 kinase (p70S6K) were measured by Western blot.Results 0.25 mmol/L LA promoted high glucose-sitmulated rat mesangial cell proliferation(P＜0.01) and entry of cell cycle into S phase(P＜0.01),along with increased phosphorylation levels of Akt,mTOR,p70S6K,and 4EBP1 (P＜0.05).These effects of 0.25 mmol/L LA disappeared when Akt activity was inhibited.On the contrary,1.0 mmol/L LA inhibited high glucose-induced cell proliferation(P＜0.01) and entry of cell cycle into S phase(P＜0.01),with the decreased phosphorylation levels of mTOR,p70S6K,and 4EBP1 (P＜ 0.05) and the enhanced activity of AMPK(P＜0.01).These effects of 1.0 mmol/L LA were prevented when AMPK activity was inhibited.Conclusions LA dose-dependently regulates mesangial cell proliferation induced by glucose via mTOR signaling pathway.