L-Carnitine attenuates angiotensin II-induced proliferation of cardiac fibroblasts: Role of NADPH oxidase inhibition and decreased sphingosine-1-phosphate generation

Hung Hsin Chao, Cheng Hsien Chen, Ju Chi Liu, Jia Wei Lin, Kar Lok Wong, Tzu-Hurng Cheng

研究成果: 雜誌貢獻文章

7 引文 斯高帕斯(Scopus)

摘要

The heart is unable to synthesize l-carnitine and is strictly dependent on the l-carnitine provided by the blood stream; however, additional studies are needed to better understand the mechanism of l-carnitine supplementation to the heart. The aim of this study was to evaluate the effects of l-carnitine on angiotensin II (Ang II)-induced cardiac fibroblast proliferation and to explore its intracellular mechanism(s). Cultured rat cardiac fibroblasts were pretreated with l-carnitine (1-30 mM) then stimulated with Ang II (100 nM). Ang II increased fibroblast proliferation and endothelin-1 expression, which were partially inhibited by l-carnitine. l-Carnitine also attenuated Ang II-induced NADPH oxidase activity, reactive oxygen species formation, extracellular signal-regulated kinase phosphorylation, activator protein-1-mediated reporter activity and sphingosine-1-phosphate generation. In addition, l-carnitine increased prostacyclin (PGI2) generation in cardiac fibroblasts. siRNA transfection of PGI2 synthase significantly reduced l-carnitine-induced PGI2 and its anti-proliferation effects on cardiac fibroblasts. Furthermore, blockading potential PGI2 receptors, including immunoprecipitation (IP) receptors and peroxisome proliferator-activated receptors alpha (PPAR?) and delta , revealed that siRNA-mediated blockage of PPAR? considerably reduced the anti-proliferation effect of l-carnitine. In summary, these results suggest that l-carnitine attenuates Ang II-induced effects (including NADPH oxidase activation, sphingosine-1-phosphate generation and cell proliferation) in part through PGI2 and PPAR?-signaling pathways.
原文英語
頁(從 - 到)580-588
頁數9
期刊Journal of Nutritional Biochemistry
21
發行號7
DOIs
出版狀態已發佈 - 七月 2010

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics
  • Medicine(all)

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