Regulation of heat shock protein 60 and 72 expression in the failing heart

Y. Wang, L. Chen, Nobuko Hagiwara, Anne A Knowlton

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Heart failure, a progressive, fatal disease of the heart muscle, is a state of chronic inflammation and injury. Heat shock protein (HSP) 72, a ubiquitous protective protein that is well-established as cardioprotective, is not increased in heart failure. In contrast, HSP60 levels are doubled in the failing heart. We hypothesized that HSF-1 is not activated in heart failure and that the increased expression of HSP60 was driven by NFκB activation. To test this hypothesis, we measured levels of heat shock factor (HSF) -1 and -2, the transcription factors controlling HSP expression, which were increased in heart failure. There was no increased phosphorylation of serine 230 or serine 303/307 in HSF-1, which are thought to regulate its activity; EMSA showed no increase in HSF binding activity with heart failure. Nonetheless, mRNA was increased for HSP60, but not HSP72. In contrast to HSF, NFκB activity was increased in heart failure. HSP60, but not HSP72, contained NFκB binding elements. ChIP assay demonstrated increased binding of NFκB to both of the NFκB binding elements in the heart failure HSP60 gene. TNFα treatment was used to test the role of NFκB activation in HSP60 expression in a cardiac cell line. TNFα increased HSP60 expression, and this could be prevented by pretreatment with siRNA inhibiting p65 expression. In conclusion, HSP72 is not increased in heart failure because HSF activity is not changed; increased expression of HSP60 may be driven by NFκB activation.

Original languageEnglish (US)
Pages (from-to)360-366
Number of pages7
JournalJournal of Molecular and Cellular Cardiology
Volume48
Issue number2
DOIs
StatePublished - Feb 2010

Keywords

  • ERK 1/2
  • GSK
  • Heart failure
  • HSP60
  • HSP72
  • NFκB

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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