Sirt 1 activator inhibits the AGE-induced apoptosis and p53 acetylation in human vascular endothelial cells

Abstract

-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.

Far-infrared protects vascular endothelial cells from advanced glycation end products-induced injury via PLZF-mediated autophagy in diabetic mice

“…AGE-BSA is not a strong apoptosis inducer. For studing apoptosis, the AGE-BSA dose often ranges between 100 and 300 μg/ml, and the treatment time is 24 or 48 h3940. The level of AGE-BSA-induced apoptosis is dose- and time-dependent.…”

Exogenous nicotinamide supplementation and moderate physical exercise can attenuate the aging process in skeletal muscle of rats

“…Because p53 is deacetylated by SIRT1 the Acp53/p53 ratio was used to assess the activity of SIRT1 (Chung et al 2015;Feng et al 2015;Kim et al 2016;Li et al 2015;Song et al 2015;Weidele et al 2017) and the results showed that exercise and NAM treatment as well as the combined effects of these increased the activity of SIRT1 in old muscle. In terms of exercise training this is similar to our earlier results (Koltai et al 2010(Koltai et al , 2012 however, the intensity of training was much less than that used in those studies.…”

Sirtuins and their interactions with transcription factors and poly(ADP-ribose) polymerases

“…SIRT1 expression increases in the conditions of H 2 O 2 -induced oxidative stress, and sirtuin activation inhibits p53-dependent apoptosis [240]. Down-regulation of SIRT1's influence on p53 mediates responses to several stressors in other cell types [204,224] and to a range of age/hyperglycaemia-related vascular endothelial pathologies [107,233]. Similar mechanisms of age-related, glucose-elicited damage might also be involved in neurodegenerative disorders along with generalized oxidative/nitrosative stress.…”