Partial inactivation of cardiac 14-3-3 protein in vivo elicits endoplasmic reticulum stress (ERS) and activates ers-initiated apoptosis in ERS-induced mice

Flori R. Sari, Kenichi Watanabe, Bambang Widyantoro, Rajarajan A. Thandavarayan, Meilei Harima, Shaosong Zhang, Anthony J. Muslin, Makoto Kodama, Yoshifusa Aizawa

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Background/Aims: Excessive endoplasmic reticulum stress (ERS) triggers apoptosis in various conditions including diabetic cardiomyopathy and pressure overload-induced cardiac hypertrophy and heart failure. The primary function of 14-3-3 protein is to inhibit apoptosis, but the roles of this protein in protecting against cardiac ERS and apoptosis are largely unknown. Methods: We investigated the roles of 14-3-3 protein in vivo during cardiac ERS and apoptosis induced by pressure overload or thapsigargin injection using transgenic (TG) mice that showed cardiac-specific expression of dominant negative (DN) 14-3-3η. Results: Cardiac positive apoptotic cells and the expression of glucose-regulated protein (GRP)78, inositol-requiring enzyme (Ire)1α, tumor necrosis factor receptor (TNFR)-associated factor (TRAF)2, CCAAT/enhancer binding protein homology protein (CHOP), caspase-12, and cleaved caspase-12 protein were significantly increased in the pressure-overload induced DN 14-3-3η mice compared with that in the WT mice. Furthermore, thapsigargin injection significantly increased the expression of GRP78 and TRAF2 expression in DN 14-3-3η mice compared with that in the WT mice. Conclusion: The enhancement of 14-3-3 protein may provide a novel protective therapy against cardiac ERS and ERS-initiated apoptosis, at least in part, through the regulation of CHOP and caspase-12 via the Ire1α/TRAF2 pathway.

Original languageEnglish (US)
Pages (from-to)167-178
Number of pages12
JournalCellular Physiology and Biochemistry
Volume26
Issue number2
DOIs
StatePublished - 2010

Keywords

  • 14-3-3
  • Apoptosis
  • Endoplasmic Reticulum stress
  • Pressure overload

ASJC Scopus subject areas

  • Physiology

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