The protective effect of alpha lipoic acid on Schwann cells exposed to constant or intermittent high glucose.
Diabetic peripheral neuropathy (DPN) is one of the most common and costly microvascular complications of diabetes, and no effective therapy exists. Previous studies have demonstrated that oxidative stress may be the unifying factor for the damaging effect of hyperglycemia. The aim of this study was to examine the impact of treatment with Alpha lipoic acid (ALA) on the intermittent high glucose (IHG) or high glucose (HG)-induced oxidative stress-induced mitochondrial pathway activation and Schwann cells (SCs) apoptosis in vitro. Our results suggested that IHG and HG induced SCs apoptosis in both caspase-dependent and caspase-independent pathways related to oxidative stress. More importantly, the cytotoxic effect of IHG was significantly more potent than that of HG. Treatment with ALA inhibited the IHG and HG-induced oxidative stress and apoptosis in SCs. Furthermore, treatment with ALA down-regulated the Bax expression and the release of cytochrome c and AIF translocation, but up-regulated the Bcl-2 expression in SCs. Treatment with ALA attenuated the activation of caspase-3 and caspase-9 and minimized the cleavage of PARP in SCs. These findings suggest that variability in glycemic control could be more deleterious than a constant HG and ALA antagonized the IHG-induced oxidative stress, activation of mitochondrial pathway and apoptosis in SCs.
Department of Endocrinology, Chinese PLA General Hospital, 28 Fu Xing Road, Beijing 100853, China.
Lian-Qing
LQ
Sun
Ying-Ying
YY
Chen
Xuan
X
Wang
Xiao-Jin
XJ
Li
Bing
B
Xue
Ling
L
Qu
Ting-Ting
TT
Zhang
Yi-Ming
YM
Mu
Ju-Ming
JM
Lu
D000080242:8-Hydroxy-2'-Deoxyguanosine / Q000031:analogs & derivatives; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000633:toxicity*; D006147:Guanine / Q000031:analogs & derivatives / Q000032:analysis; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018384:Oxidative Stress; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012583:Schwann Cells / Q000187:drug effects*; D012584:Sciatic Nerve / Q000166:cytology; D008063:Thioctic Acid / Q000737:chemistry* / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
D051033:Apoptosis Inducing Factor; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D006147:Guanine; C078307:8-oxo-7,8-dihydrodeoxyguanine; D008063:Thioctic Acid; D000080242:8-Hydroxy-2'-Deoxyguanosine; D045304:Cytochromes c; D005947:Glucose