Possible involvement of phosphorylated heat-shock factor-1 in changes in heat shock protein 72 induction in the failing rat heart following myocardial infarction.

Abstract

It is supposed that an increase in the level of heat shock protein 72 (HSP72) in the failing heart would be beneficial for reducing the myocardial damage. However, the induction of HSP72 after an exposure to heat shock is blunted in the failing rat heart following myocardial infarction. In this study, to clarify the possible mechanisms underlying this reduction in the ability for HSP72 induction in the failing heart, the possible involvement of heat-shock factor-1 (HSF1), an HSP transcription factor, in this reduction was examined. When hemodynamic parameters of rats with myocardial infarction 8 weeks after coronary artery ligation were measured, the animals showed the signs of chronic heart failure. The HSF1 content was increased in the viable myocardium in the failing heart. The ability to induce cardiac HSP72 was reduced after an exposure to hyperthermia. The level of HSF1 in the cytosolic fraction from the failing heart with or without exposure to hyperthermia was increased, whereas that of HSF1 in the nuclear fraction was reduced. In the failing heart, the level of HSF1 on its serine 303 (Ser303) residue, which phosphorylation represses HSF1, was increased. These findings suggest that HSF1 translocation from the cytosol into the nucleus was attenuated after an exposure to hyperthermia and that an increase in the phosphorylation of HSF1 Ser303 was involved in the impairment of heat shock-induced HSP72 induction in the failing heart following myocardial infarction.

• Authors: Tetsuro Marunouchi, Mao Murata, Norio Takagi, Kouichi Tanonaka
• Journal: Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 36 Issue 8 Pg. 1332-40 ( 2013) ISSN: 1347-5215 [Electronic] Japan
• PMID: 23902977 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA-Binding Proteins
• HSP72 Heat-Shock Proteins
• Heat Shock Transcription Factors
• Hsf1 protein, rat
• Transcription Factors
• Glycogen Synthase Kinase 3 beta
• Proto-Oncogene Proteins c-akt
• Glycogen Synthase Kinase 3

Topics

• Animals
• DNA-Binding Proteins (metabolism)
• Fever (metabolism, pathology, physiopathology)
• Glycogen Synthase Kinase 3 (metabolism)
• Glycogen Synthase Kinase 3 beta
• HSP72 Heat-Shock Proteins (metabolism)
• Heat Shock Transcription Factors
• Male
• Myocardial Infarction (metabolism, pathology, physiopathology)
• Myocardium (metabolism, pathology)
• Organ Size
• Proto-Oncogene Proteins c-akt (metabolism)
• Rats
• Rats, Wistar
• Transcription Factors (metabolism)
• Ventricular Pressure