title: Venlafaxine protects methylglyoxal-induced apoptosis in the cultured human brain microvascular endothelial cells.
abstract: It was reported that venlafaxine protects microvascular endothelial cells injury in several models. But the mechanisms of venlafaxine protects cell injury still poor understanding. Here, we shows that in the cultured human brain microvascular endothelial cells (HBMEC), we found that venlafaxine protects methylglyoxal (MGO)-induced cell injury, and the venlafaxine significant reduction in the level of reactive oxygen species, down-regulated expression of pro-apoptotic activated caspase-3 and Bax, increased BDNF release and expression of anti-apoptotic Bcl-2 in the cultured HBMEC. Furthermore, we found that venlafaxine inhibits MGO-induced phosphorylation of JNK. Moreover, venlafaxine increased AKT phosphorylation and the protective effects of venlafaxine was inhibited by PI3K/AKT inhibitor. These findings suggest that venlafaxine protects MGO-induced HBMEC injury through PI3K/AKT and JNK pathway as the potential underlying mechanisms of HBMEC injury in diabetes.
authors.affiliation: Cancer Institute, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Lv
authors.affiliation: Department of Neurology, Ningbo No. 2 Hospital, Ningbo 315000, China.
authors.forename: Chengyao
authors.initials: C
authors.lastname: Gu
authors.affiliation: Department of Neurology, Ningbo No. 2 Hospital, Ningbo 315000, China. Electronic address: nb-ccj163com@163.com.
authors.forename: Caijing
authors.initials: C
authors.lastname: Chen
mesh_terms: D000928:Antidepressive Agents / Q000494:pharmacology*; D017209:Apoptosis; D001921:Brain / Q000098:blood supply*; D002460:Cell Line; D003511:Cyclohexanols / Q000494:pharmacology*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D055806:Microvessels / Q000166:cytology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011765:Pyruvaldehyde / Q000494:pharmacology*; D000069470:Venlafaxine Hydrochloride
chemical_list: D000928:Antidepressive Agents; D003511:Cyclohexanols; D018696:Neuroprotective Agents; D011765:Pyruvaldehyde; D000069470:Venlafaxine Hydrochloride; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases
keywords: Apoptosis; Human brain microvascular endothelial cells; Methylglyoxal; Reactive oxygen species; Venlafaxine