Attenuation of CHOP-mediated myocardial apoptosis in pressure-overloaded dominant negative p38α mitogen-activated protein kinase mice

Flori R. Sari, Bambang Widyantoro, Rajarajan A. Thandavarayan, Meilei Harima, Arun Lakshmanan, Shaosong Zhang, Anthony J. Muslin, Kenji Suzuki, Makoto Kodama, Kenichi Watanabe

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Background/Aims: Pressure overload stimulation is known to elicit disturbances in the endoplasmic reticulum (ER), which leads to ER stress (ERS). p38 mitogen-activated protein kinase (MAPK) plays an important role in mediating apoptotic processes, however, the roles of this kinase in activating ERS-initiated apoptosis in pressure-overloaded hearts are largely unknown. Methods: We clarified the role of p38α MAPK in ERS-associated apoptosis by subjecting transgenic mice displaying cardiac specific dominant negative (DN) mutant p38α MAPK over-expression to seven day pressure overload. Results: Seven days pressure overload resulted in the same extent of cardiac hypertrophy and ERS in the wild-type (WT) and DN p38α mice compared with the sham mice. It also activated inositol-requiring enzyme (Ire)-1α and its downstream molecule, tumor necrosis factor receptor (TNFR)-associated factor (TRAF)2 in the WT and DN p38α mice compared with the sham mice. Interestingly, increased myocardial apoptosis and the up-regulation of CCAAT/enhancer binding protein homology protein (CHOP) expression compared with those in the sham mice were found in the aortic-banded WT mice, but not in the DN p38α mice. Conclusion: Partial inhibition of p38α protein blocked the activation of CHOP-mediated apoptotic processes during pressure overload by partially inhibiting signaling from the Ire-1α/TRAF2 to its down-stream molecule, CHOP.

Original languageEnglish
Pages (from-to)487-496
Number of pages10
JournalCellular Physiology and Biochemistry
Volume27
Issue number5
DOIs
Publication statusPublished - 27 Jun 2011
Externally publishedYes

Fingerprint

CCAAT-Enhancer-Binding Proteins
p38 Mitogen-Activated Protein Kinases
Apoptosis
Pressure
Proteins
Inositol
TNF Receptor-Associated Factor 2
Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
Endoplasmic Reticulum Stress
Cardiomegaly
Enzymes
Endoplasmic Reticulum
Transgenic Mice
Phosphotransferases
Up-Regulation

Keywords

  • Apoptosis
  • Endoplasmic reticulum stress
  • p38 MAPK
  • Pressure overload

ASJC Scopus subject areas

  • Physiology

Cite this

Attenuation of CHOP-mediated myocardial apoptosis in pressure-overloaded dominant negative p38α mitogen-activated protein kinase mice. / Sari, Flori R.; Widyantoro, Bambang; Thandavarayan, Rajarajan A.; Harima, Meilei; Lakshmanan, Arun; Zhang, Shaosong; Muslin, Anthony J.; Suzuki, Kenji; Kodama, Makoto; Watanabe, Kenichi.

In: Cellular Physiology and Biochemistry, Vol. 27, No. 5, 27.06.2011, p. 487-496.

Research output: Contribution to journalArticle

Sari, FR, Widyantoro, B, Thandavarayan, RA, Harima, M, Lakshmanan, A, Zhang, S, Muslin, AJ, Suzuki, K, Kodama, M & Watanabe, K 2011, 'Attenuation of CHOP-mediated myocardial apoptosis in pressure-overloaded dominant negative p38α mitogen-activated protein kinase mice', Cellular Physiology and Biochemistry, vol. 27, no. 5, pp. 487-496. https://doi.org/10.1159/000329970
Sari, Flori R. ; Widyantoro, Bambang ; Thandavarayan, Rajarajan A. ; Harima, Meilei ; Lakshmanan, Arun ; Zhang, Shaosong ; Muslin, Anthony J. ; Suzuki, Kenji ; Kodama, Makoto ; Watanabe, Kenichi. / Attenuation of CHOP-mediated myocardial apoptosis in pressure-overloaded dominant negative p38α mitogen-activated protein kinase mice. In: Cellular Physiology and Biochemistry. 2011 ; Vol. 27, No. 5. pp. 487-496.
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AU - Lakshmanan, Arun

AU - Zhang, Shaosong

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