Peroxisome proliferator-activated receptor-alpha ligands inhibit cardiac lipoprotein lipase activity.

نویسندگان

  • R Carroll
  • D L Severson
چکیده

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that regulate gene expression of lipoprotein lipase (LPL) in liver and adipose tissue. We examined the direct effect of PPAR-alpha ligands on LPL catalytic activity in cultured cardiomyocytes from adult rat heart. After overnight culture (16 h), 1 microM Wy-14643 and 10 microM BM-17.0744 decreased total cellular LPL activity to approximately 50% of control with no change in enzyme synthesis or mass; as a consequence, PPAR-alpha activation produced a significant decrease in LPL specific activity (mU/ng LPL protein). Wy-14643 and BM-17.0744 also reduced heparin-releasable LPL activity and mass in the culture medium. Inhibition of LPL activity by Wy-14643 did not reduce the ability of insulin plus dexamethasone to stimulate cellular and heparin-releasable LPL activities. A similar inhibitory effect on cellular and heparin-releasable LPL activity was observed when cardiomyocytes were cultured with 60 microM linoleic acid. In conclusion, two different PPAR-alpha ligands (Wy-14643 and BM-17.0744) inhibited cellular LPL activity in cultured cardiomyocytes by a posttranscriptional and posttranslational mechanism.

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عنوان ژورنال:
  • American journal of physiology. Heart and circulatory physiology

دوره 281 2  شماره 

صفحات  -

تاریخ انتشار 2001