کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1950751 | 1055696 | 2012 | 10 صفحه PDF | دانلود رایگان |
α-Lipoic acid (LA) has been shown to improve the diabetic cardiac symptoms. However, the underlying mechanisms have not been elucidated precisely. We have reported recently that LA potentially protected neurons from substance-induced apoptosis. We hypothesized that LA could attenuate cardiac cells death induced by oxidative stress derived from high glucose. To test this possibility, we examined the effects of LA on d-glucose/glucose oxidase (DG/GO, 30 mM/5 mU)-induced injury in rat cardiomyoblast H9c2 cells. We observed that LA pretreatment significantly increased cell viability in DG/GO-challenged cells. LA pretreatment also attenuated DG/GO-induced apoptosis as evidenced by decreases in both nuclear condensation and loss of mitochondrial potential. In addition, LA activated ERK1/2 and moderately increased ROS production. Blockade of ERK1/2 activation by PD98059 completely abolished LA-induced protection against DG/GO challenge. Inhibition of ROS by N-acetylcysteine abrogated LA-induced ERK1/2 activation and cytoprotection. Furthermore, we observed that the ROS production induced by LA was significantly slower and milder than that by DG/GO. Our results suggest that pretreatment with LA moderately increased ROS production to induce a preconditioning-like effect by ERK1/2 activation thereby increased tolerance of H9c2 cells to DG/GO challenge.
► α-Lipoic acid (LA) prevented d-glucose/glucose oxidase (DG/GO) induced H9c2 cell injury.
► LA activated ERK1/2 and increased ROS generation.
► Inhibition of ERK1/2 activation abolished LA-induced protection against DG/GO challenge.
► Inhibition of ROS increase abrogated LA-induced cytoprotection and ERK1/2 activation.
► Our data suggest that LA-induced cytoprotection was mediated by ROS-dependent ERK1/2 activation.
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research - Volume 1823, Issue 4, April 2012, Pages 920–929