Heme oxygenase-1 contributes to the cytoprotection of alpha-lipoic acid via activation of p44/42 mitogen-activated protein kinase in vascular smooth muscle cells.
Alpha-lipoic acid (ALA) is a natural antioxidant that scavenges reactive oxygen species (ROS) and regenerates or recycles endogenous antioxidants. ALA has recently been reported to protect against oxidative injury in various disease processes. The aim of this study was to investigate whether the antioxidant effect of ALA is mediated by the induction of heme oxygenase (HO)-1 in rat aortic smooth muscle cells (A10 cells). ALA significantly induced HO-1 expression accompanied by an increase in HO activity in A10 cells. Pretreatment with ALA increased the resistance of A10 cells to hydrogen-peroxide-induced oxidant stress. This protection of ALA was abrogated in the presence of the HO inhibitor zinc protoporphyrin IX. ALA significantly increased ROS, and this effect was blocked by N-acetyl-cysteine, which also inhibited ALA-induced activation of p44/42 mitogen-activated protein kinase (MAPK) and AP-1, HO-1 expression, and HO activity. These results suggest that ALA induces HO-1 expression through the production of ROS and subsequent activation of the p44/42 MAPK pathway and AP-1 in vascular smooth muscle cells. This study demonstrated that ALA increases the expression of HO-1, a critical cytoprotective molecule, and identified a novel pleiotropic effect of ALA on cardiovascular protection.
Cheng
Pao-Yun
PY
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
Lee
Yen-Mei
YM
Shih
Neng-Lang
NL
Chen
Yao-Chang
YC
Yen
Mao-Hsiung
MH
D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D020935:MAP Kinase Signaling System; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000201:enzymology*; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000235:genetics; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D008063:Thioctic Acid / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism
D017382:Reactive Oxygen Species; D018808:Transcription Factor AP-1; D008063:Thioctic Acid; D004247:DNA; D006861:Hydrogen Peroxide; D051547:Heme Oxygenase-1; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3