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

Hanming Zhang, Xuejun Wang

Research output: Contribution to journalReview article

4 Citations (Scopus)

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

Fingerprint

Cyclic GMP-Dependent Protein Kinases
Proteasome Endopeptidase Complex
Proteins
Hemostasis
Cardiac Myocytes
Quality Control
Proteolysis
Heart Failure
Sildenafil Citrate
Pharmaceutical Preparations

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

Cite this

Priming the proteasome by protein kinase G : A novel cardioprotective mechanism of sildenafil. / Zhang, Hanming; Wang, Xuejun.

In: Future Cardiology, Vol. 11, No. 2, 01.03.2015, p. 177-189.

Research output: Contribution to journalReview article

@article{4fd3e093bd87498f863672f780d13546,
title = "Priming the proteasome by protein kinase G: A novel cardioprotective mechanism of sildenafil",
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.",
keywords = "bortezomib, cyclic GMP-dependent protein kinase, desmin-related cardiomyopathy, methoctramine, phosphodiesterase inhibitor, pilocarpine, protein quality control, sildenafil, ubiquitin proteasome system",
author = "Hanming Zhang and Xuejun Wang",
year = "2015",
month = "3",
day = "1",
doi = "10.2217/fca.15.3",
language = "English (US)",
volume = "11",
pages = "177--189",
journal = "Future Cardiology",
issn = "1479-6678",
publisher = "Future Medicine Ltd.",
number = "2",

}

TY - JOUR

T1 - Priming the proteasome by protein kinase G

T2 - A novel cardioprotective mechanism of sildenafil

AU - Zhang, Hanming

AU - Wang, Xuejun

PY - 2015/3/1

Y1 - 2015/3/1

N2 - 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.

AB - 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.

KW - bortezomib

KW - cyclic GMP-dependent protein kinase

KW - desmin-related cardiomyopathy

KW - methoctramine

KW - phosphodiesterase inhibitor

KW - pilocarpine

KW - protein quality control

KW - sildenafil

KW - ubiquitin proteasome system

UR - http://www.scopus.com/inward/record.url?scp=84924667866&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84924667866&partnerID=8YFLogxK

U2 - 10.2217/fca.15.3

DO - 10.2217/fca.15.3

M3 - Review article

C2 - 25760877

AN - SCOPUS:84924667866

VL - 11

SP - 177

EP - 189

JO - Future Cardiology

JF - Future Cardiology

SN - 1479-6678

IS - 2

ER -