Thus we hypothesised that high selenium intake could cause ED through ER stress.Įndothelial cells were treated with selenite (0.5–20 μM) in the presence or absence of the ER chemical chaperone, 4-phenylbutryic acid (PBA). High selenium doses cause apoptosis in some cancer cells through the induction of endoplasmic reticulum (ER) stress response, a mechanism also involved in the pathogenesis of insulin resistance and endothelial dysfunction (ED). However the underpinning molecular mechanisms involved are not clear. Selenium is associated with insulin resistance and may therefore affect endothelial function, increasing type II diabetes risk and associated cardiovascular-disease risk. This work also underscores the therapeutic potential of HO-1 induction against hyperglycaemia-mediated endothelial dysfunction. These results highlight the importance of oxidative stress both in initiating or maintaining ER stress response and in mediating ER stress-induced damage and cell death in endothelial cells. The mRNA expression of inflammatory cytokine IL-6 was enhanced in cells incubated with high glucose while those pre-treated with PBA or CoPP were prevented. Also, cells incubated with high glucose had enhanced apoptosis, increased protein expression of cleaved PARP and caspase-7 in addition to enhanced caspases 3/7 activity while cells pre-treated with either PBA or CoPP were totally protected. Interestingly, the pre-treatment of cells with PBA or CoPP significantly reduced high glucose-mediated ER stress and oxidative stress in cells. High glucose treatment in cells increased protein and mRNA expression of several ER stress response markers (BIP, CHOP, ATF4) and enhanced ROS production in addition to reducing NO release. Also, apoptosis and caspase 3/7 activity were assessed. The productions of ROS (flow cytometer) and NO (Griess assay) were analysed. Then, ER stress response was assessed (PCR, western blot). We aim in this project to test the hypothesis that HO-1 induction will protect against high glucose-mediated ER stress and oxidative stress in endothelial cells and will enhance cell survival.Įndothelial cells were cultured in physiological or high concentrations of glucose in the presence of cobalt protoporphyrin 1X (CoPP, HO-1 inducer), 4-phenylbutyrate (PBA, chemical chaperone to inhibit ER stress) or vehicle. Hemeoxygenase-1 (HO-1) induction was shown to protect against oxidative stress in diabetes however the underlying molecular mechanisms have not yet been fully elucidated. Much evidence highlighted the complex interplay between Endoplasmic Reticulum (ER) stress and oxidative stress in the pathogenesis of diabetes. Diabetes is intimately associated with cardiovascular complications.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |