PKD deletion promotes autophagy and inhibits hypertrophy in cardiomyocyte

Di Zhao1, Yan Gao2, Wei Wang3

  • 1Postdoctoral Mobile Station of Shandong University of Traditional Chinese Medicine, Shandong, China; Department of Cardiology, Affiliated Hospital of Shandong Academy of Medical Sciences, Shandong, China; Department of Cardiology, Jinan Central Hospital Affiliated to Shandong University, Shandong, China.

Experimental Cell Research
|November 24, 2019
PubMed

Insights

Protein kinase D (PKD) promotes cardiac hypertrophy by inhibiting autophagy. Inhibiting PKD or enhancing autophagy prevents this heart condition, revealing a key regulatory pathway.

Area of Science:

  • Cardiovascular Biology
  • Molecular Cell Biology
  • Biochemistry

Background:

  • Cardiac hypertrophy is a significant risk factor for heart failure.
  • The precise molecular mechanisms underlying cardiac hypertrophy remain incompletely understood.
  • Protein kinase D (PKD) is implicated in cardiac hypertrophy development.

Purpose of the Study:

  • To investigate the role of Protein kinase D (PKD) in cardiac hypertrophy.
  • To elucidate the mechanism by which PKD influences cardiomyocyte size and function.
  • To test the hypothesis that PKD negatively regulates autophagy in cardiomyocytes during hypertrophy.

Main Methods:

  • Primary neonatal rat cardiomyocyte culture.
  • Norepinephrine-induced cardiomyocyte hypertrophy model.
  • PKD knockdown (siRNA) and overexpression studies.
  • Autophagy modulation using Rapamycin and 3-MA.
  • Analysis of cardiomyocyte size, hypertrophy biomarkers (ANP, BNP), and autophagy markers.
  • Western blot and electron microscopy.

Main Results:

  • Norepinephrine induced cardiomyocyte hypertrophy, increasing ANP and BNP mRNA levels.
  • PKD knockdown and Rapamycin significantly attenuated norepinephrine-induced hypertrophy.
  • PKD knockdown enhanced autophagy and downregulated the AKT/mTOR/S6K pathway.
  • Autophagy inhibition (3-MA) reversed the protective effects of PKD knockdown.
  • PKD overexpression suppressed autophagy.

Conclusions:

  • PKD plays a crucial role in mediating cardiac hypertrophy.
  • PKD regulates cardiac hypertrophy by negatively controlling autophagy.
  • The PKD-mediated regulation of autophagy occurs via the AKT/mTOR/S6K signaling pathway.

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