Cardiac muscle cell hypertrophy and apoptosis induced by distinct members of the p38 mitogen-activated protein kinase family

Yibin Wang, Shuang Huang, Valerie P. Sah, John Ross, Joan Heller Brown, Jiahuai Han, Kenneth R. Chien

Research output: Contribution to journalArticle

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Abstract

p38 mitogen-activated protein (MAP) kinase activities were significantly increased in mouse hearts after chronic transverse aortic constriction, coincident with the onset of ventricular hypertrophy. Infection of cardiomyocytes with adenoviral vectors expressing up-stream activators for the p38 kinases, activated mutants of MAP kinase kinase 3b(E) (MKK3bE) and MAP kinase kinase 6b(E) (MKK6bE), elicited characteristic hypertrophic responses, including an increase in cell size, enhanced sarcomeric organization, and elevated atrial natriuretic factor expression. Overexpression of the activated MKK3bE in cardiomyocytes also led to an increase in apoptosis. The hypertrophic response was enhanced by co-infection of an adenoviral vector expressing wild type p38β, and was suppressed by the p38β dominant negative mutant. In contrast, the MKK3bE-induced cell death was increased by co-infection of an adenovirus expressing wild type p38α, and was suppressed by the dominant negative p38α mutant. This provides the first evidence in any cell system for divergent physiological functions for different members of the p38 MAP kinase family. The direct involvement of p38 pathways in cardiac hypertrophy and apoptosis suggests a significant role for p38 signaling in the pathophysiology of heart failure.

Original languageEnglish (US)
Pages (from-to)2161-2168
Number of pages8
JournalJournal of Biological Chemistry
Volume273
Issue number4
DOIs
StatePublished - Jan 23 1998

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Mitogen-Activated Protein Kinase Kinases
p38 Mitogen-Activated Protein Kinases
Cardiac Myocytes
Hypertrophy
Muscle
Cells
Apoptosis
Coinfection
Cardiomegaly
Atrial Natriuretic Factor
Cell death
Cell Size
Adenoviridae
Constriction
Cell Death
Phosphotransferases
Heart Failure
Infection

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Cardiac muscle cell hypertrophy and apoptosis induced by distinct members of the p38 mitogen-activated protein kinase family. / Wang, Yibin; Huang, Shuang; Sah, Valerie P.; Ross, John; Brown, Joan Heller; Han, Jiahuai; Chien, Kenneth R.

In: Journal of Biological Chemistry, Vol. 273, No. 4, 23.01.1998, p. 2161-2168.

Research output: Contribution to journalArticle

Wang, Yibin ; Huang, Shuang ; Sah, Valerie P. ; Ross, John ; Brown, Joan Heller ; Han, Jiahuai ; Chien, Kenneth R. / Cardiac muscle cell hypertrophy and apoptosis induced by distinct members of the p38 mitogen-activated protein kinase family. In: Journal of Biological Chemistry. 1998 ; Vol. 273, No. 4. pp. 2161-2168.
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