Heat stress-induced phosphorylation of FoxO3a signalling in rat skeletal muscle.
A recent study demonstrated that FoxO3a was directly induced by the overexpression of Hsp72 in rat soleus muscle. However, whether heat stress treatment induces FoxO3a phosphorylation in rat skeletal muscle remains unclear. This study examined the effects of heat stress on the regulation of the FoxO3a signalling pathway in rat skeletal muscle.



Thirty-two male Wistar rats (15 weeks old) were randomly assigned into two groups; sedentary control group (Sed, n = 8) and experimental group (n = 24). After an overnight fast, one leg of each rat (HS leg) in the experimental group was immersed in hot water (43 °C) for 30 min, and the soleus and plantaris muscles in both legs were removed immediately (0 min), 30 min, 60 min, or 24 h after the heat stress (n = 6 each group). The contralateral, non-heated leg in the experimental group served as an internal control (CT leg).



Heat stress treatment resulted in a significant increase in FoxO3a phosphorylation (Ser253) in the soleus and plantaris muscles of heat-stressed legs after 24 h. Hsp72 expression in heat-stressed legs was significantly higher at 60 min and 24 h in these muscles. Activation of the PTEN/Akt and MEK/ERK pathways was also observed in these muscles immediately after stress, but not at 24 h. There were no differences in FoxO1 and AMPKα phosphorylation in either muscle.



Heat stress in rat skeletal muscle induces phosphorylation of FoxO3a signalling, and it may be related to Hsp72 upregulation, and the activation of the PTEN/Akt and MEK/ERK pathways.
Graduate School of Health and Sports Science, Juntendo University, Inzai, Chiba, Japan. t-yoshih@juntendo.ac.jp.
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Yoshihara
Graduate School of Health and Sports Science, Juntendo University, Inzai, Chiba, Japan.|Mito Medical Center, Tsukuba University Hospital, Mito, Ibaraki, Japan.
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Kobayashi
Faculty of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan.
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Kakigi
Faculty of Education, Yamaguchi University, Yamaguchi, Yamaguchi, Japan.
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Sugiura
Graduate School of Health and Sports Science, Juntendo University, Inzai, Chiba, Japan.
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Naito
D000818:Animals; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D000071316:Forkhead Box Protein O3 / Q000378:metabolism*; D050884:HSP72 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006358:Hot Temperature; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology*; D013312:Stress, Physiological / Q000502:physiology*; D015854:Up-Regulation
C499515:FOXO3 protein, rat; D000071316:Forkhead Box Protein O3; D050884:HSP72 Heat-Shock Proteins; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D051059:PTEN Phosphohydrolase
extracellular signal-related kinase; forkhead box O; heat shock protein 72; protein kinase B/Akt