Priming the proteasome by protein kinase G: A novel cardioprotective mechanism of sildenafil

Hanming Zhang, Xuejun Wang

Research output: Contribution to journalReview articlepeer-review

4 Scopus citations

Abstract

The proteasome mediates the degradation of most cellular proteins including misfolded proteins, pivotal to intracellular protein hemostasis. Proteasome functional insufficiency is implicated in a large subset of human failing hearts. Experimental studies have established proteasome functional insufficiency as a major pathogenic factor, rationalizing proteasome enhancement as a potentially new therapeutic strategy for congestive heart failure. Protein kinase G activation known to be cardioprotective was recently found to facilitate proteasomal degradation of misfolded proteins in cardiomyocytes; sildenafil was shown to activate myocardial protein kinase G, improve cardiac protein quality control and slow down the progression of cardiac proteinopathy in mice. This identifies the first clinically used drug that is capable of benign proteasome enhancement and unveils a potentially novel cardioprotective mechanism for sildenafil.

Original languageEnglish (US)
Pages (from-to)177-189
Number of pages13
JournalFuture Cardiology
Volume11
Issue number2
DOIs
StatePublished - Mar 1 2015

Keywords

  • bortezomib
  • cyclic GMP-dependent protein kinase
  • desmin-related cardiomyopathy
  • methoctramine
  • phosphodiesterase inhibitor
  • pilocarpine
  • protein quality control
  • sildenafil
  • ubiquitin proteasome system

ASJC Scopus subject areas

  • Molecular Medicine
  • Cardiology and Cardiovascular Medicine

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