Aging abolishes the cardioprotective effect of combination heat shock and hypoxic preconditioning in reperfused rat hearts

Yukako Honma, Masato Tani, Michiyo Takayama, Ken Yamamura, Hiroshi Hasegawa

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Hypoxic preconditioning (HP) does not improve post-ischemic function in the hearts of aging rats secondary to failure of protein kinase C (PKC) activation, but the effect of heat shock (HS) or preconditioning has not been studied. We studied whether HS increases tolerance to ischemia and whether its combination with HP would restore the cardioprotective effect in aging rat hearts. HS was performed in 12- and 50-week-old rats. Hearts were isolated and subjected to HP by 10 min hypoxic perfusion before 25 min ischemia followed by 30 min reperfusion 48 h after HS. Both HP and HS improved recovery of left ventricular function with translocation of PKC-δ from the cytosol to the nuclear fraction and induction of heat shock proteins, HSP27, HSP70, and αB-crystallin. The combination of HS and HP enhanced the translocation of PKC-δ in young rats, resulting in further improvement in functional recovery. In older rats, HP translocated PKC-δ from the membrane to the cytosol fraction, but did not improve functional recovery, although the combination of HS with HP induced HS proteins and translocated PKC-δ from the cytosol to the nuclear fraction. HS provided cardioprotection and had additive effects to HP with additional PKC-δ activation in young rats. However, in hearts from aging rats, HS alone was not cardioprotective, nor was its combination with HP, despite the induction of HS proteins and the activation of PKC-δ, resulting in its translocation to the nuclear fraction.

Original languageEnglish
Pages (from-to)489-495
Number of pages7
JournalBasic Research in Cardiology
Volume97
Issue number6
DOIs
Publication statusPublished - 2002 Nov 1

Keywords

  • Aging
  • Heat shock
  • Heat shock protein
  • Hypoxic preconditioning
  • Protein kinase C

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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