Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 407, Issue 3, Pages 227-235Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S0014-2999(00)00758-5
Keywords
apoptosis; smooth muscle cell, vascular; p53; Gadd45; troglitazone; pioglitazone
Categories
Ask authors/readers for more resources
Thiazolidinediones, activators of peroxisome proliferator-activated receptor (PPAR)gamma, have been reported to induce apoptosis in many types of cells. In the present study, we investigated the effects of thiazolidinediones, troglitazone, and pioglitazone on the cell growth of vascular smooth muscle cells, and identified a specific effect of troglitazone in addition to PPAR gamma activation. Subconfluent rat culture Vascular smooth muscle cells were treated with or without PPAR gamma activators, troglitazone (1-30 muM), or pioglitazone (1-30 muM) for 72 h. After treatment, cell viability was significantly reduced by troglitazone in concentration of 5-30 muM but not by pioglitazone. Vascular smooth muscle cells appeared to float and shrink 48 h after treatment with 20 muM of troglitazone. In situ DNA labeling showed that the nuclei of these cells were positively stained, and genomic DNA extracted from the cells showed nucleosomal laddering. Messenger RNA expression levels of c-myc, p21, bax, bcl-2, and bcl-x were not changed by the treatment with troglitazone. In contrast, along with the induction of vascular smooth muscle cell apoptosis, both the mRNA and protein expression levels of p53 and Gadd45 markedly increased in response to troglitazone. These results strongly suggest that troglitazone can induce vascular smooth muscle cell apoptosis and that this effect is caused primarily by activation of the p53 and Gadd45 pathway but not by PPAR gamma activation. (C) 2000 Elsevier Science B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available