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Protein kinase D participates in cardiomyocyte hypertrophy by regulating extracellular signal-regulated and myocyte

Haitao Yuan1, Qian Xiang1, Le Yang1

  • 1Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, PR China.

Revista Portuguesa De Cardiologia
|December 18, 2020
PubMed

Insights

The protein kinase C epsilon/protein kinase D/extracellular signal-regulated kinase 5/myocyte enhancer factor 2D pathway is crucial for cardiomyocyte hypertrophy in response to angiotensin II, offering new therapeutic targets for hypertension.

Area of Science:

  • Cardiovascular Biology
  • Molecular Cardiology
  • Cell Signaling

Background:

  • Cardiomyocyte hypertrophy is a key characteristic of hypertension, but the underlying molecular signaling pathways are not fully understood.
  • Identifying these pathways is critical for developing targeted therapies to manage hypertensive heart disease.

Purpose of the Study:

  • To investigate the role of a hypothesized protein kinase D (PKD)-dependent extracellular signal-regulated kinase 5 (ERK5) pathway in regulating myocyte enhancer factor 2D (MEF2D) and mediating prohypertrophic responses to angiotensin II (Ang II).

Main Methods:

  • Utilized neonatal rat cardiomyocytes and employed Western blot, real-time quantitative PCR, and immunofluorescence staining to analyze signaling molecule activation and translocation.
  • Assessed cardiomyocyte hypertrophy by measuring atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) expression and [3H]-leucine incorporation.

Main Results:

  • Angiotensin II stimulation increased phosphorylated protein kinase D (p-PKD) and extracellular signal-regulated kinase 5 (p-ERK5) levels in cardiomyocytes.
  • Silencing protein kinase C epsilon (PKCɛ) reduced p-PKD levels, and the PKD pathway mediated Ang II-induced ERK5 translocation.
  • Inhibition of PKCɛ, PKD, and ERK5 attenuated Ang II-induced MEF2D activation, ANP/BNP expression, and hypertrophy.

Conclusions:

  • This study elucidates the PKCɛ/PKD/ERK5/MEF2D signaling cascade as a novel pathway involved in angiotensin II-induced cardiomyocyte hypertrophy.
  • These findings provide significant insights into the molecular mechanisms of hypertensive cardiac remodeling and suggest potential therapeutic targets.
Abstract

Keywords:
CardiomiócitosCardiomyocytesERK5Extracellular signal-regulated protein kinase 5HipertrofiaHypertrophyMEF2DMyocyte enhancer factor 2DProtein kinase C epsilonProtein kinase DProteína quinase CProteína quinase D

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