Sirt 1 activator inhibits the AGE-induced apoptosis and p53 acetylation in human vascular endothelial cells.
Advanced glycation end products (AGEs) by nonenzymatic glycation reactions are extremely accumulated in the diabetic vascular cells, neurons, and glia, and are confirmed to play important role in the pathogenesis of diabetes mellitus -induced cardiovascular complications. Sirt 1, known as mammalian sirtuin, has been recognized to regulate insulin secretion and protect cells against oxidative stress, which is promoted by the accumulated AGEs in cardiovascular cells. In the present study, we treated human endothelial Eahy926 cells with AGEs, and determined the apoptosis induction, caspase activation, the Sirt 1 activity, the expression and acetylation of p53. Then we manipulated Sirt 1 activity with a Sirt 1 activator, Resveratrol (RSV), and a Sirt 1 inhibitor, sirtinol, in the AGE-BSA-treated Eahy926 cells, and then re-evaluated the apoptosis induction, caspase activation, the expression and acetylation of p53. Results demonstrated that AGEs induced apoptosis in the human endothelial Eahy926 cells, by promoting the cytochrome c release, activation of caspase 9/3. Also, the AGE-BSA treatment promoted the total p53 level and acetylated (Ac) p53, but reduced the Sirt 1 level and activity. On the other hand, the Sirt 1 inhibitor/activator not only deteriorated/ameliorated the promotion to p53 level and Ac p53, but also aggravated/inhibited the AGE-induced apoptosis and the promotion to apoptosis-associated signaling molecules. In conclusion, the present study confirmed the apoptosis promotion by AGEs in endothelial Eahy926 cells, by regulating the Sirt 1 activity and p53 signaling, it also implies the protective role of Sirt 1 activator against the AGE-induced apoptosis.
Department of Emergency Room, the Affiliated Hospital of Qingdao University, China.
Peng
P
Li
Lina
L
Zhang
Changyong
C
Zhou
Nan
N
Lin
Aiguo
A
Liu
D000107:Acetylation / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics*; D001549:Benzamides / Q000494:pharmacology*; D002318:Cardiovascular Diseases / Q000209:etiology; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism; D003920:Diabetes Mellitus / Q000209:etiology; D042783:Endothelial Cells / Q000378:metabolism / Q000502:physiology*; D017127:Glycation End Products, Advanced / Q000009:adverse effects*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D009284:Naphthols / Q000494:pharmacology*; D018384:Oxidative Stress / Q000235:genetics; D000077185:Resveratrol; D015398:Signal Transduction / Q000235:genetics* / Q000502:physiology*; D056564:Sirtuin 1 / Q000502:physiology*; D013267:Stilbenes / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D001549:Benzamides; D017127:Glycation End Products, Advanced; D007328:Insulin; D009284:Naphthols; D013267:Stilbenes; D016159:Tumor Suppressor Protein p53; C439060:sirtinol; D045304:Cytochromes c; D020169:Caspases; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D000077185:Resveratrol