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Acta Pharmacol Sin. 2007 Aug;28(8):1116-22.

Tanshinone IIA inhibits endothelin-1 production in TNF-alpha-induced brain microvascular endothelial cells through suppression of endothelin-converting enzyme-1 synthesis.

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  • 1Department of Neurosurgery, the First Affiliated Hospital, China Medical University, Shenyang, China.

Abstract

AIM:

To investigate the effects of tanshinone IIA (Tan IIA) on the regulation of the production of endothelin (ET)-1 (including large ET-1), mRNA levels of ET-1, endothelin-converting enzyme-1 (ECE-1), endothelin-A receptor (ETA) and endothelin-B receptor (ETB) induced by TNF-alpha in rat brain microvascular endothelial cells (BMVEC).

METHODS:

The ET-1 release (including large ET-1) into the culture medium was determined by enzyme immunoassay. The levels of ET-1, ECE-1, ETA, and ETB mRNA were measured by RT-PCR. Endothelin receptor binding was also tested.

RESULTS:

The induction of ET-1 release by TNF-alpha from cultured BMVEC was dose-dependently reduced by Tan IIA, but large ET-1 levels progressively increased in response to Tan IIA; the mRNA expression of ET-1 was unaffected. Tan IIA also caused a decrease in ETA receptor mRNA and ECE-1 expression in a dose-dependent manner. Endothelin receptor binding was unaltered in BMVEC stimulated with TNF-alpha alone or a combination of TNF-alpha and Tan IIA.

CONCLUSION:

These findings suggest that Tan IIA may inhibit ET-1 production in TNF-alpha-induced BMVEC through the suppression of ECE-1 synthesis.

PMID:
17640471
[PubMed - indexed for MEDLINE]
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