High glucose inhibits apoptosis induced by serum deprivation in vascular smooth muscle cells via upregulation of Bcl-2 and Bcl-xl.
Apoptosis plays a critical role in normal vascular development and atherosclerosis. To test the hypothesis that diabetic vasculopathy may be due in part to altered apoptosis pathways, we investigated the effects of high glucose treatment on serum withdrawal-induced apoptosis, expression of Bcl-2 family members, and inhibitor of apoptosis protein (IAP)-1 in vascular smooth muscle cells (VSMCs). Treatment with a high concentration of glucose (22 mmol/l) significantly attenuated apoptosis in response to serum withdrawal in cultured rat VSMCs compared with cells treated with a normal glucose concentration (5.5 mmol/l). This attenuation was accompanied by a significant decrease in the caspase-3 activity in comparison with the normal glucose group. Furthermore, exposure of VSMCs to high glucose markedly increased the abundance of Bcl-2 and Bcl-xl mRNAs compared with treatment with normal glucose, while expression of bax and IAP-1 mRNA remained unchanged. Our results suggest that high glucose suppresses serum withdrawal-induced apoptosis in VSMCs by upregulating expression of Bcl-2 and Bcl-xl, suggesting that enhanced expression of antiapoptotic proteins may play an important role in the development of macrovascular complications in diabetes.
Li
Haikun
H
Research Service, John D. Dingell Veterans Administration Medical Center, Detroit, Michigan, USA.
Télémaque
Sabine
S
Miller
Richard E
RE
Marsh
James D
JD
D000818:Animals; D001011:Aorta; D017209:Apoptosis / Q000187:drug effects*; D001483:Base Sequence; D018929:Cell Culture Techniques; D016895:Culture Media, Serum-Free; D017931:DNA Primers; D005947:Glucose / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D051034:Inhibitor of Apoptosis Proteins; D008353:Mannitol / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D011506:Proteins / Q000187:drug effects / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051020:bcl-X Protein
C494813:Bcl2l1 protein, rat; D016895:Culture Media, Serum-Free; D017931:DNA Primers; D051034:Inhibitor of Apoptosis Proteins; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051020:bcl-X Protein; D008353:Mannitol; D005947:Glucose