Alpha-lipoic acid defends homocysteine-induced endoplasmic reticulum and oxidative stress in HAECs.

Oxidative stress and endoplasmic reticulum (ER) stress play vital roles in the development of atherosclerosis. And hyperhomocysteinemia (HHCY) has been recognized as an independent risk factor for this process. Alpha-lipoic acid, a disulphide-containing compound, can scavenge reactive oxygen species, inhibit the formation of free radicals and chelate metal to maintain the homeostasis in the cells. This study aimed to determine the protecting effects of Alpha-lipoic acid (ALA) on homocysteine (HCY) induced injuries to human aortic endothelial cells (HAECs) and uncover the underlying mechanisms. HAECs were treated with ALA in the presence/absence of HCY. The mechanism of ALA against HCY-induced cell injury was evaluated using Western blotting, real-time RT-PCR. Reactive oxygen Species (ROS) was detected by flow cytometry analysis. Mitochondrial membrane potential in HCY-treated HAECs was measured by Rhodamine 123 staining, and the samples were observed by confocal laser scanning microscopy. ALA suppressed the HCY-stimulated ROS generation, as well as the NF-κB transcriptional activation, and ICAM-1, VCAM-1 expression. ALA also elevated the bcl-2 and reduced caspase3, 9 expressions in the HCY- induced HAECs. Simultaneously, ALA could inhibit activation of ER stress-associated sensors GRP78, IRE1α, ATF6, P-PERK, P-eIF2α, CHOP and ATF4 induced by HCY. In addition, using GSH inhibitor, we proved ALA reduced the expressions of GRP78, ATF4 and IRE1α by generating GSH. ALA ameliorated HCY-induced ER stress and oxidation then reduced cells apoptosis and inflammation. These results suggested ALA played a key role in regulating ER homeostasis in atherosclerosis.

Hu H ，Wang C ，Jin Y ，Meng Q ，Liu Q ，Liu K ，Sun H ... -  《-》

Catalpol Inhibits Homocysteine-induced Oxidation and Inflammation via Inhibiting Nox4/NF-κB and GRP78/PERK Pathways in Human Aorta Endothelial Cells.

Hu H ，Wang C ，Jin Y ，Meng Q ，Liu Q ，Liu Z ，Liu K ，Liu X ，Sun H ... -  《-》

Madecassic Acid protects against hypoxia-induced oxidative stress in retinal microvascular endothelial cells via ROS-mediated endoplasmic reticulum stress.

Madecassic acid (MA) is an abundant triterpenoid in Centella asiatica (L.) Urban. (Apiaceae) that has been used as a wound-healing, anti-inflammatory and anti-cancer agent. Up to now, the effects of MA against oxidative stress remain unclear. In this study, we investigated the effect of MA and its mechanisms on hypoxia-induced human Retinal Microvascular Endothelial Cells (hRMECs). hRMECs were pre-treated with different concentrations of MA (0-50μM) for 30min before being incubated under hypoxia condition (37°C, 5% CO2 and 95% N2). Cell apoptosis was evaluated with MTT assay and TUNEL staining, and the expression of apoptosis- and endoplasmic reticulum (ER) stress-related molecules was assessed with western blotting and RT-PCR analysis. Intracellular ROS level was evaluated using DCFH-DA. Intracellular malondialdehyde (MDA), dehydrogenase (LDH), glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD) were evaluated using related Kits. Activating transcription factor 4 (ATF4) nuclear translocation was assessed with western blotting analysis and immunofluorescence staining. MA significantly reduced oxidative stress in hypoxia-induced hRMECs, as shown by increased cell viability, SOD and GSH-PX leakage, decreased TUNEL- and ROS-positive cell ratio, LDH and MDA leakage, caspase-3 and -9 activity, and Bax/Bcl-2 ratio. In addition, MA also attenuated hypoxia-induced ER stress in hRMECs, as shown by reduced mRNA levels of glucose-regulated protein 78 (GRP78), C/EBP homologous transcription factor (CHOP), protein levels of cleaved activating transcription factor 6 (ATF6) and inositol-requiring kinase/endonuclease 1 alpha (IRE1α), phosphorylation of pancreatic ER stress kinase (PERK) and eukaryotic initiation factor 2 alpha (eIF2α), cleaved caspase-12 and ATF4 translocation to nucleus. The current study indicated that the regulation of oxidative stress and ER stress by MA would be a promising therapy to reverse the process and development of hypoxia-induced hRMECs dysfunction.

Yang B ，Xu Y ，Hu Y ，Luo Y ，Lu X ，Tsui CK ，Lu L ，Liang X ... -  《-》

Cholestin (Monascus purpureus rice) inhibits homocysteine-induced reactive oxygen species generation, nuclear factor-kappaB activation, and vascular cell adhesion molecule-1 expression in human aortic endothelial cells.

Lin CP ，Chen YH ，Chen JW ，Leu HB ，Liu TZ ，Liu PL ，Huang SL ... -  《-》

Piceatannol attenuates homocysteine-induced endoplasmic reticulum stress and endothelial cell damage via heme oxygenase-1 expression.

Kil JS ，Jeong SO ，Chung HT ，Pae HO ... -  《-》