title: δ-Tocopherol prevents methylglyoxal-induced apoptosis by reducing ROS generation and inhibiting apoptotic signaling cascades in human umbilical vein endothelial cells.
abstract: Methylglyoxal (MGO) is a highly reactive metabolite of glucose, which is known to cause damage and induce apoptosis in endothelial cells. Endothelial cell damage is implicated in the progression of diabetes-associated complications and atherosclerosis. Nuts are high in vitamin E. Consumption of nuts has been recommended for the prevention of cardiovascular disease. However, different nuts contain different forms of vitamin E, which can have different effects on endothelial cells. In this work, we investigated the protective effect of different isoforms of vitamin E on MGO-induced apoptosis in human umbilical vein endothelial cells (HUVECs). Among all forms of vitamin E, δ-tocopherol showed the highest effect on apoptosis of HUVECs. We also compared the anti-apoptotic activity of δ-tocopherol with that of α-tocopherol in MGO-treated HUVECs. Pretreatment with α- or δ-tocopherol significantly inhibited MGO-induced changes in cell morphology, cell death, and production of intracellular reactive oxygen species. δ-Tocopherol prevented MGO-induced apoptosis in HUVECs by increasing Bcl-2 expression and decreasing Bax expression. Interestingly, α-tocopherol also inhibited these factors but to a lesser extent than δ-tocopherol. MGO was found to activate mitogen-activated protein kinases (MAPKs). Compared to pretreatment with α-tocopherol, pretreatment with δ-tocopherol more strongly inhibited the activation of MAPKs, such as JNK and ERK1/2. These findings suggest that δ-tocopherol may be a more effective regulator of MGO-induced apoptosis than α-tocopherol.
authors.affiliation: College of Pharmacy, Gachon University, Incheon, Republic of Korea. sunnykim@gachon.ac.kr.
authors.forename: Moon ho
authors.initials: Mh
authors.lastname: Do
authors.forename: Su nam
authors.initials: Sn
authors.lastname: Kim
authors.forename: Seung-Yong
authors.initials: SY
authors.lastname: Seo
authors.forename: Eui-Ju
authors.initials: EJ
authors.lastname: Yeo
authors.forename: Sun Yeou
authors.initials: SY
authors.lastname: Kim
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D011765:Pyruvaldehyde / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D024505:Tocopherols / Q000494:pharmacology*
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D011765:Pyruvaldehyde; D020928:Mitogen-Activated Protein Kinases; C479072:delta-tocopherol; D024505:Tocopherols