Endothelin-1 production is enhanced by rotenone, a mitochondrial complex I inhibitor, in cultured rat cardiomyocytes

Koh Ichi Yuhki, Takashi Miyauchi, Yoshihiko Kakinuma, Nobuyuki Murakoshi, Seiji Maeda, Katsutoshi Goto, Iwao Yamaguchi, Takahiko Suzuki*

*この研究の対応する著者

研究成果: Article査読

20 被引用数 (Scopus)

抄録

In chronic heart failure and acute myocardial infarction, the tissue level of endothelin (ET) -1 in the heart, as well as its plasma level, has been reported to increase markedly. There is, however, little information about what in these pathologic conditions leads to increased production of ET-1, and which type of cell in the heart produces ET-1. We examined the mRNA and peptide expression of ET-1 using cultured rat neonatal cardiomyocytes, in which mitochondrial dysfunction was induced by rotenone, a mitochondrial respiratory chain complex I inhibitor, because one of the common features in failing or ischemic hearts is an alteration in energy metabolism due to mitochondrial dysfunction. Rotenone increased glucose use by the culture cells within 12 h of addition without affecting cell viability, and depressed the mitochondrial membrane potential after 72 h, indicating the induction of mitochondrial dysfunction in cardiomyocytes. Rotenone induced significant increase in the expression level of mRNA for ET-1 within 1 h of addition. In accordance with this finding, immunoreactive ET-1 in culture medium increased 3 times after 24 h of incubation, suggesting active secretion of ET-1 from cultured cells treated with rotenone. Immunocytochemical analysis verified significant increase of ET-1 peptide in cardiomyocytes, confirming the production of ET-1 by cardiomyocytes. These results suggest that derangement of mitochondrial function in cardiomyocytes itself could lead to the increased production of ET-1 in cardiomyocytes, and that this mechanism may contribute to the increased production of ET-1 in failing and ischemic hearts.

本文言語English
ページ(範囲)850-858
ページ数9
ジャーナルJournal of Cardiovascular Pharmacology
38
6
DOI
出版ステータスPublished - 2001
外部発表はい

ASJC Scopus subject areas

  • 薬理学
  • 循環器および心血管医学

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