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Regulation of expression of contractile proteins with cardiac hypertrophy and failure

Martin, Xavier J. ; Wynne, Dylan G. ; Glennon, Peter E. ; Moorman, Anton F. M. ; Boheler, Kenneth R. ;
  • 초록  

    Abstract Transitions in sarcomeric α-actin and cardiac myosin heavy chain (MHC) gene expression have been useful as molecular markers for the development of cardiac hypertrophy and failure. In simpler model systems, α-actin expression has been useful in delineating some of the molecular pathways responsible for its induction following growth stimulation in vitro . In this study, we report that the effects of adrenergic agonists on α-actin expression in neonatal cardiocytes is dependent upon the culture conditions. In cardiocytes plated at 5 x 10 4 cells/cm 2 , skeletal α-actin mRNA levels represent 47%, 37% or 42% of total sarcomeric α-actin accumulations following administrations of 4 μM norepinephrine (NE), isoproterenol (Iso), or phenylephrine (PE), respectively. Cultured cardiocytes treated with vehicle (ascorbate) only accumulated 19% skeletal α-actin. Under these tissue culture conditions, in contrast to data reported previously, skeletal α-actin expression is regulated by both α- and &bgr;-adrenergic agonist stimulation. Furthermore, we present data showing that an endogenous anti-&bgr;-MHC transcript is regulated by both pressure-overload- or thyroxine-induced cardiac hypertrophy. Although anti-&bgr;-MHC transcripts do not play a major role in regulating &bgr;-MHC gene expression, the presence of this antisense transcript is associated with a novel set of &bgr;-MHC degradation products. In vitro studies, where oligonucleotides complementary to &bgr;-MHC have been introduced into cardiomyoctyes, show that the mRNA levels of &bgr;-MHC are decreased by 14–21 % within 72 h after addition of the oligonucleotides. This result together with the presence of &bgr;-MHC degradation products suggest that endogenous anti-&bgr;-MHC transcripts may be involved in a post-transcriptional regulatory mechanism affecting the steady-state levels of &bgr;-MHC expression.


  • 주제어

    sarcomeric α-actins .   myosin heavy chains .   neonatal rat cardiocytes .   adrenergic agonists .   antisense RNA .   oligonucleotides.  

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