αB-Crystallin gene induction and phosphorylation by MKK6-activated p38: A potential role for αB-Crystallin as a target of the p38 branch of the cardiac stress response

H. E. Hoover, D. J. Thuerauf, J. J. Martindale, C. C. Glembotski

Research output: Contribution to journalArticlepeer-review

138 Scopus citations

Abstract

The MAPK kinase MKK6 selectively stimulates p38 MAPK and confers protection against stress-induced apoptosis in cardiac myocytes. However, the events lying downstream of p38 that mediate this protection are unknown. The small heat shock protein, αB-crystallin, which is expressed in only a few cell types, including cardiac myocytes, may participate in MKK6-mediated cytoprotection. In the present study, we showed that, in cultured cardiac myocytes, expression of MKK6(Glu), an active form of MKK6, led to p38-dependent increases in αB-crystallin mRNA, protein, and transcription. MKK6(Glu) also induced p38-dependent activation of the downstream MAPK-activated protein kinase, MAP-KAP-K2, and the phosphorylation of αB-crystallin on serine-59. Initially, exposure of cells to the hyperosmotic stressor, sorbitol, stimulated MKK6, p38, and MAP-KAP-K2 and increased phosphorylation of αB-crystallin on serine 59. However, after longer times of exposure to sorbitol, the cells began to undergo apoptosis. This sor-bitol-induced apoptosis was increased when p38 was inhibited in a manner that would block αB-crystallin induction and phosphorylation. Thus, under these conditions, the activation of MKK6, p38, and MAPKAP-K2 by sorbitol can provide a degree of protection against stress-induced apoptosis. Supporting this view was the finding that sorbitol-induced apoptosis was nearly completely blocked in cells expressing MKK6(Glu). Therefore, the cytoprotective effects of MKK6 in cardiac myocytes are due, in part, to phosphorylation of αB-crystallin on serine 59 and to the induction of αB-crystallin gene expression.

Original languageEnglish (US)
Pages (from-to)23825-23833
Number of pages9
JournalJournal of Biological Chemistry
Volume275
Issue number31
DOIs
StatePublished - Aug 4 2000
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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