Role of TRPM7 channels in hyperglycemia-mediated injury of vascular endothelial cells.
This study investigated the change of transient receptor potential melastatin 7 (TRPM7) expression by high glucose and its role in hyperglycemia induced injury of vascular endothelial cells. Human umbilical vein endothelial cells (HUVECs) were incubated in the presence or absence of high concentrations of D-glucose (HG) for 72 h. RT-PCR, Real-time PCR, Western blotting, Immunofluorescence staining and whole-cell patch-clamp recordings showed that TRPM7 mRNA, TRPM7 protein expression and TRPM7-like currents were increased in HUVECs following exposure to HG. In contrast to D-glucose, exposure of HUVECs to high concentrations of L-glucose had no effect. HG increased reactive oxygen species (ROS) generation, cytotoxicity and decreased endothelial nitric oxide synthase protein expression, which could be attenuated by knockdown of TRPM7 with TRPM7 siRNA. The protective effect of silencing TRPM7 against HG induced endothelial injury was abolished by U0126, an inhibitor of the extracellular signal-regulated kinase signaling pathway. These observations suggest that TRPM7 channels play an important role in hyperglycemia-induced injury of vascular endothelial cells.
Department of Cardiology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China ; Neuroscience Institute, Morehouse School of Medicine, Atlanta, Georgia, United States of America.
Huawei
H
Sun
Tiandong
T
Leng
Zhao
Z
Zeng
Xiuren
X
Gao
Koichi
K
Inoue
Zhi-Gang
ZG
Xiong
D002070:Butadienes / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D020868:Gene Silencing; D005947:Glucose / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D006943:Hyperglycemia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D050053:TRPM Cation Channels / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D002070:Butadienes; D009570:Nitriles; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D050053:TRPM Cation Channels; C113580:U 0126; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D017346:Protein Serine-Threonine Kinases; C486583:TRPM7 protein, human; D005947:Glucose