The thiazolidinedione drug troglitazone up-regulates nitric oxide synthase expression in vascular endothelial cells

• Published in: Journal of diabetes and its complications 2006-09, Vol.20 (5), p.336-342
• Main Authors: Goya, Kayoko, Sumitani, Satoru, Otsuki, Michio, Xu, Xin, Yamamoto, Hiroyasu, Kurebayashi, Shogo, Saito, Hiroshi, Kouhara, Haruhiko, Kasayama, Soji
• Format: Article
• Language: English
• Subjects: alpha-Tocopherol - metabolism; Analysis of Variance; Cells, Cultured; Chromans - pharmacology; Endothelial Cells - cytology; Endothelial Cells - drug effects; Endothelial Cells - enzymology; Endothelium; Enzymes; Humans; Hypoglycemic Agents - pharmacology; Nitric oxide; Nitric Oxide Synthase Type III - drug effects; Nitric Oxide Synthase Type III - genetics; Nitric Oxide Synthase Type III - metabolism; Peroxisome proliferator-activated receptor; Prostaglandin D2 - analogs & derivatives; Prostaglandin D2 - metabolism; RNA, Messenger - analysis; Rodents; Studies; Thiazolidinedione; Thiazolidinediones - pharmacology; Umbilical Veins - cytology; Umbilical Veins - enzymology; Up-Regulation; Vasodilation - drug effects; Vasodilation - physiology
• ISSN: 1056-8727; 1873-460X
• DOI: 10.1016/j.jdiacomp.2005.08.003

Endothelial dysfunction is a phenomenon often observed in diabetic patients, which is a cause for vascular complications of diabetes mellitus. Endothelium-derived nitric oxide (NO) is responsible for vasodilatation, and NO-dependent vasodilatation is diminished in diabetic patients. In the present study, we evaluated the effects of thiazolidinediones (TZDs), antidiabetic drugs known to improve insulin resistance and to have vasodilating properties, on endothelial NO synthase (eNOS) expression in cultured vascular endothelial cells. Human umbilical vein endothelial cells were treated with the TZDs troglitazone and pioglitazone, or the peroxisome proliferator-activated receptor (PPAR) γ activator 15-deoxy-Δ 12,14-prostaglandin J 2 (15-dPGJ2). The expression of eNOS protein and its mRNA was determined by Western and Northern blot analyses, respectively. The effect of α-tocopherol that possesses structural similarity to troglitazone was also examined. Troglitazone up-regulated eNOS protein and its mRNA levels, whereas pioglitazone and 15-dPGJ2 failed to increase their levels. By contrast, α-tocopherol also increased in eNOS protein and mRNA. These results suggest that troglitazone up-regulates eNOS expression probably through its 6-hydroxychromanes structure but not activating PPARγ.