Sex differences in forkhead box O3a signaling response to hindlimb unloading in rat soleus muscle

• Published in: The journal of physiological sciences Vol. 69; no. 2; pp. 235 - 244
• Main Authors: Yoshihara, Toshinori, Natsume, Toshiharu, Tsuzuki, Takamasa, Chang, Shuo-Wen, Kakigi, Ryo, Sugiura, Takao, Naito, Hisashi
• Format: Journal Article
• Language: English
• Published: Japan Springer 01.03.2019; BioMed Central; Springer Japan
• Subjects: Animals; Ethylenediaminetetraacetic acid; Female; Forkhead Box Protein O3 - metabolism; Forkhead protein; FOXO3 protein; Gender differences; Heat shock proteins; Hindlimb - metabolism; Hindlimb - physiology; Hindlimb Suspension - physiology; HSP72 Heat-Shock Proteins - metabolism; Hsp72 protein; Male; Males; Muscle, Skeletal - metabolism; Muscle, Skeletal - physiology; Myostatin; Myostatin - metabolism; Original Paper; Phosphorylation; Phosphorylation - physiology; Proteasome Endopeptidase Complex - metabolism; Proteasomes; Rats; Rats, Wistar; Rodents; Sex Characteristics; Sex differences; Signal transduction; Signal Transduction - physiology; Soleus muscle; Ubiquitin; Ubiquitin - metabolism; Ubiquitination; Unloading; Hindlimb unloading; Myostatin; Heat shock protein 72; Soleus muscle; Sex difference; Forkhead box O
• ISSN: 1880-6546; 1880-6562
• DOI: 10.1007/s12576-018-0640-6

We tested the hypothesis that there are sex differences in hindlimb unloading-induced activation of the forkhead box subfamily O3a (FoxO3a) signaling pathway in rat soleus muscle. Age-matched male and female Wistar rats were subjected to hindlimb unloading, and the soleus muscle was removed before or 1 or 7 days after unloading. Female rats showed greater percent changes in relative soleus muscle weight than males. FoxO3a phosphorylation was lower in females than in males and was associated with higher levels of protein ubiquitination 7 days after unloading. Heat shock protein 72 (Hsp72) levels were lower in female rats and increased in males during unloading. Female rats showed slightly higher myostatin levels, which showed a non-significant decline in male rats following unloading. Thus, males and females show different responses to the FoxO3a/ubiquitin-proteasome pathway following hindlimb unloading in rat soleus muscle, which may be associated with differences in Hsp72 expression and myostatin signaling.