Induction of heat-shock protein 70 expression by geranylgeranylacetone shows cytoprotective effects in cardiomyocytes of mice under humid heat stress.
BACKGROUND
Increasing evidence has revealed that humid heat stress (HHS) causes considerable damage to human health. The cardiovascular system has been suggested to be the primary target of heat stress, which results in serious cardiovascular diseases. However, there is still a lack of effective approaches for the prevention and treatment of cardiovascular diseases induced by HHS.


OBJECTIVE
Heat-shock proteins (Hsps), especially Hsp70, are reported to provide effective cytoprotection under various stress stimuli. In the present study, we evaluated the cytoprotective effect of geranylgeranylacetone (GGA), which was previously been reported to induce Hsp70 expression in cardiomyocytes under HHS.


RESULTS
Using a mouse model of HHS, we showed that the pretreatment of GGA enhanced Hsp70 expression under HHS, as examined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. We then examined the effect of GGA pretreatment on the cardiomyocyte apoptosis induced by HHS using terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) staining, and found that GGA pretreatment inhibited mitochondria-mediated apoptosis. GGA pretreatment could reverse the effect of HHS on cell apoptosis by increasing expression of Bcl-2, decreasing cytochrome c in cytosol, and increasing cytochrome c in mitochondria. However, GGA pretreatment had no effect on the oxidative stress induced by HHS as determined by levels of superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH).


CONCLUSIONS
We have demonstrated that GGA pretreatment suppressed HHS-induced apoptosis of cardiomyocytes through the induction of Hsp70 overexpression.
Center of Cardiovascular Surgery, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, China.
Xiaowu
X
Wang
Center of Cardiovascular Surgery, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, China.
Binbin
B
Yuan
Center of Cardiovascular Surgery, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, China.
Wenpeng
W
Dong
Center of Cardiovascular Surgery, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, China.
Bo
B
Yang
Center of Cardiovascular Surgery, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, China.
Yongchao
Y
Yang
Center of Cardiovascular Surgery, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, China.
Xi
X
Lin
Department of Anesthesiology, General Hospital of Chengdu Military Command, Chengdu, China.
Gu
G
Gong
D000818:Animals; D004224:Diterpenes / Q000494:pharmacology*; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis* / Q000378:metabolism; D018869:Heat-Shock Response; D006813:Humidity; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
D004224:Diterpenes; D018840:HSP70 Heat-Shock Proteins; C031049:geranylgeranylacetone