Activation of mitogen-activated protein kinases and p90 ribosomal S6 kinase in failing human hearts with dilated cardiomyopathy

Yasuchika Takeishi, Qunhua Huang, Jun Ichi Abe, Wenyi Che, Jiing Dwan Lee, Hisaaki Kawakatsu, Brian D. Hoit, Bradford C. Berk, Richard A. Walsh

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

Objective: A new member of the MAP kinase family, big MAP kinase-1 (BMK1), has been recently identified to promote cell growth and attenuate apoptosis. P90 ribosomal S6 kinase (p90RSK), one of the potentially important substrates of extracellular signal regulated kinase (ERK), regulates gene expression in part via phosphorylation of CREB and the Na+/H+ exchanger. Recently, we have demonstrated that the activity of BMK1, Src (the upstream regulator of BMK1) and p90RSK was increased in hypertrophied myocardium induced by pressure-overload in the guinea pig. However, the abundance and activity of these kinases in human hearts are unknown. Methods: In addition to the three classical MAP kinases (ERK, p38 kinase, and c-Jun NH2-terminal kinase (JNK)), we examined the protein expression and activity of Src, BMK1, and p90RSK in explanted hearts from patients with dilated cardiomyopathy (n=9). Normal donor hearts, which were not suitable for transplant for technical reasons, were used as controls (n=5). Results: There were no significant differences in the levels of protein expression of these kinases between normal and failing hearts. ERK1/2 and p90RSK were activated in heart failure compared to control (P<0.01 and P<0.03, respectively), while the activity of p38 kinase was decreased (P<0.05) and the activity of JNK was unchanged in heart failure. By contrast, the activities of Src and BMK1 were significantly reduced in end-stage heart failure compared to normal donor hearts (P<0.05). Conclusion: These data suggest that multiple MAP kinases, p90RSK, and Src are differentially regulated in human failing myocardium of patients with idiopathic dilated cardiomyopathy and may be involved in the pathogenesis of this complex disease.

Original languageEnglish (US)
Pages (from-to)131-137
Number of pages7
JournalCardiovascular Research
Volume53
Issue number1
DOIs
StatePublished - Jan 10 2002

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90-kDa Ribosomal Protein S6 Kinases
Mitogen-Activated Protein Kinase 7
Dilated Cardiomyopathy
Mitogen-Activated Protein Kinases
Phosphotransferases
Heart Failure
JNK Mitogen-Activated Protein Kinases
Extracellular Signal-Regulated MAP Kinases
Myocardium
Tissue Donors
Sodium-Hydrogen Antiporter
Protein Kinases
Guinea Pigs
Phosphorylation
Apoptosis
Transplants
Gene Expression
Pressure
Growth

Keywords

  • Cardiomyopathy
  • Heart failure
  • Protein kinases
  • Signal transduction

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Activation of mitogen-activated protein kinases and p90 ribosomal S6 kinase in failing human hearts with dilated cardiomyopathy. / Takeishi, Yasuchika; Huang, Qunhua; Abe, Jun Ichi; Che, Wenyi; Lee, Jiing Dwan; Kawakatsu, Hisaaki; Hoit, Brian D.; Berk, Bradford C.; Walsh, Richard A.

In: Cardiovascular Research, Vol. 53, No. 1, 10.01.2002, p. 131-137.

Research output: Contribution to journalArticle

Takeishi, Yasuchika ; Huang, Qunhua ; Abe, Jun Ichi ; Che, Wenyi ; Lee, Jiing Dwan ; Kawakatsu, Hisaaki ; Hoit, Brian D. ; Berk, Bradford C. ; Walsh, Richard A. / Activation of mitogen-activated protein kinases and p90 ribosomal S6 kinase in failing human hearts with dilated cardiomyopathy. In: Cardiovascular Research. 2002 ; Vol. 53, No. 1. pp. 131-137.
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T1 - Activation of mitogen-activated protein kinases and p90 ribosomal S6 kinase in failing human hearts with dilated cardiomyopathy

AU - Takeishi, Yasuchika

AU - Huang, Qunhua

AU - Abe, Jun Ichi

AU - Che, Wenyi

AU - Lee, Jiing Dwan

AU - Kawakatsu, Hisaaki

AU - Hoit, Brian D.

AU - Berk, Bradford C.

AU - Walsh, Richard A.

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AB - Objective: A new member of the MAP kinase family, big MAP kinase-1 (BMK1), has been recently identified to promote cell growth and attenuate apoptosis. P90 ribosomal S6 kinase (p90RSK), one of the potentially important substrates of extracellular signal regulated kinase (ERK), regulates gene expression in part via phosphorylation of CREB and the Na+/H+ exchanger. Recently, we have demonstrated that the activity of BMK1, Src (the upstream regulator of BMK1) and p90RSK was increased in hypertrophied myocardium induced by pressure-overload in the guinea pig. However, the abundance and activity of these kinases in human hearts are unknown. Methods: In addition to the three classical MAP kinases (ERK, p38 kinase, and c-Jun NH2-terminal kinase (JNK)), we examined the protein expression and activity of Src, BMK1, and p90RSK in explanted hearts from patients with dilated cardiomyopathy (n=9). Normal donor hearts, which were not suitable for transplant for technical reasons, were used as controls (n=5). Results: There were no significant differences in the levels of protein expression of these kinases between normal and failing hearts. ERK1/2 and p90RSK were activated in heart failure compared to control (P<0.01 and P<0.03, respectively), while the activity of p38 kinase was decreased (P<0.05) and the activity of JNK was unchanged in heart failure. By contrast, the activities of Src and BMK1 were significantly reduced in end-stage heart failure compared to normal donor hearts (P<0.05). Conclusion: These data suggest that multiple MAP kinases, p90RSK, and Src are differentially regulated in human failing myocardium of patients with idiopathic dilated cardiomyopathy and may be involved in the pathogenesis of this complex disease.

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KW - Protein kinases

KW - Signal transduction

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