The thiazolidinedione drug troglitazone up-regulates nitric oxide synthase expression in vascular endothelial cells.
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) gamma activator 15-deoxy-Delta(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 alpha-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, alpha-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 PPARgamma.
Goya
Kayoko
K
Department of Molecular Medicine, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
Sumitani
Satoru
S
Otsuki
Michio
M
Xu
Xin
X
Yamamoto
Hiroyasu
H
Kurebayashi
Shogo
S
Saito
Hiroshi
H
Kouhara
Haruhiko
H
Kasayama
Soji
S
D000704:Analysis of Variance; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D052250:Nitric Oxide Synthase Type III / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D045162:Thiazolidinediones / Q000494:pharmacology*; D000077288:Troglitazone; D014471:Umbilical Veins / Q000166:cytology / Q000201:enzymology; D015854:Up-Regulation; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D024502:alpha-Tocopherol / Q000378:metabolism
D002839:Chromans; D007004:Hypoglycemic Agents; D012333:RNA, Messenger; D045162:Thiazolidinediones; C037112:9-deoxy-delta-9-prostaglandin D2; D052250:Nitric Oxide Synthase Type III; D024502:alpha-Tocopherol; D000077288:Troglitazone; D015230:Prostaglandin D2