Rosiglitazone inhibits high glucose-induced apoptosis in human umbilical vein endothelial cells through the PI3K/Akt/eNOS pathway.
Previous studies have shown that the phosphatidylinositol 3-kinase / Akt / endothelial nitric oxide synthase / NO (PI3K/Akt/eNOS/NO) pathway is involved in high glucose-induced endothelial cell apoptosis and rosiglitazone has a protective effect on endothelium. In the present study, we investigated the antiapoptotic effect of rosiglitazone on human umbilical vein endothelial cells (HUVECs) exposed to high glucose and explored its possible mechanism. Treatment of high glucose (33 mmol/L) for 48 h significantly induced the apoptosis of HUVECs, concomitantly with increased caspase-3 activity. High glucose treatment also decreased Akt and eNOS phosphorylation levels with subsequent NO production. All these alterations induced by high glucose were attenuated by rosiglitazone (1 micromol/L). Interestingly, the antiapoptotic effect of rosiglitazone was inhibited by PI3K inhibitor (LY294002, wortmannin) or eNOS inhibitor NG-<span class="smallcap">l</span>-nitro-arginine methyl ester (<span class="smallcap">l</span>-NAME). The reverse effects of rosiglitazone on phosphorylation of Akt and eNOS with subsequent NO production were also inhibited by LY294002, wortmannin or <span class="smallcap">l</span>-NAME, respectively. These findings suggest that rosiglitazone inhibits high glucose-induced apoptosis in HUVECs through the PI3K/Akt/eNOS pathway.
Wu
Jing
J
Department of Endocrinology, Xiang-Ya Hospital, Central South University, 87 Xiang-Ya Road, Changsha 410008, China.
Lei
Min-Xiang
MX
Xie
Xiao-Yun
XY
Liu
Lan
L
She
Yan-Mei
YM
Mo
Juan
J
Wang
Shan
S
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology; D005947:Glucose / Q000008:administration & dosage* / Q000037:antagonists & inhibitors* / Q000633:toxicity; D006801:Humans; D052250:Nitric Oxide Synthase Type III / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D000077154:Rosiglitazone; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D045162:Thiazolidinediones / Q000494:pharmacology*; D014471:Umbilical Veins / Q000187:drug effects / Q000502:physiology
D045162:Thiazolidinediones; D000077154:Rosiglitazone; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose