Differential effects among thiazolidinediones on the transcription of thromboxane receptor and angiotensin II type 1 receptor genes

A. Sugawara, K. Takeuchi, A. Uruno, Y. Ikeda, S. Arima, K. Sato, M. Kudo, Y. Taniyama, S. Ito

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)

Abstract

Peroxisome proliferator-activated receptor (PPAR)-γ ligands thiazolidinediones (TZDs) have recently been reported to be anti-hypertensive and anti-atherosclerotic. We have previously shown that one of the TZDs troglitazone significantly suppressed the transcription of both thromboxane receptor (TXR) and angiotensin II type 1 receptor (AT1R) genes in vascular smooth muscle cells (VSMCs) by activating PPAR-γ. In the present study, we compared the effects of troglitazone and other TZDs on the transcription of these genes. TXR and AT1R mRNAs in rat VSMCs were determined by semi-quantitative RT-PCR. Luciferase chimeric constructs containing either the 989-bp rat TXR gene promoter or the 1,969-bp rat AT1R gene promoter were transiently transfected into VSMCs. The cells were incubated with troglitazone, RS-1455 (a derivative of troglitazone which does not contain the hindered phenol resembling α-tocopherol), pioglitazone, or rosiglitazone for 12 h before harvesting. mRNA expression levels of TXR and AT1R were significantly decreased by troglitazone in contrast to rosiglitazone. TXR gene and AT1R gene transcription was significantly suppressed by troglitazone in a dose-dependent manner, while RS-1455 was less potent. Pioglitazone and rosiglitazone weakly suppressed the transcription of both genes in a manner almost similar to RS-1455. We have shown that troglitazone suppresses transcription of both the TXR and AT1R genes more potently than other TZDs. The structure of troglitazone and RS-1455 is identical except the hindered phenol, which is recently recognized to function as an antioxidant. Moreover, we have shown that the potency for activating PPAR-γ is almost identical between troglitazone and RS-1455. We therefore speculate that the strong transcriptional suppression of the TXR and AT1R genes by troglitazone may be mediated in part by its antioxidant effect.

Original languageEnglish
Pages (from-to)229-233
Number of pages5
JournalHypertension Research
Volume24
Issue number3
DOIs
Publication statusPublished - 2001

Keywords

  • Antioxidant
  • PPAR-γ
  • Pioglitazone
  • Rosiglitazone
  • Troglitazone
  • α-tocopherol

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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