Effects Of Endurance Exercise On Jnk, Hsp72, And Nf-kB Activation In Oletf Skeletal Muscle

Abstract

Redox-sensitive kinases and HSP72 (heat shock protein) have been reported to be associated with the development and protection of type 2 diabetes, respectively. Exercise training has been proved to serve as a therapeutic method for the treatment of type 2 diabetes. However, little is known about how exercise exerts protective effect on type 2 diabetes through regulation of redox-sensitive kinase and HSP72. PURPOSE: To investigate the effect of 12 weeks of treadmill exercise training on the expression of stress kinases including JNK (c-Jun NH2-terminal kinase) and IKK (IkB kinase), HSP72, and NF-kB activation in type 2 diabetic OLETF (Otsuka Long-Evans Tokushima Fatty) rat skeletal muscle. METHODS: The OLETF rats were randomly divided into exercise training group (Ex-OLETF, n=8) and sedentary group (Sed-OLETF, n=8), and the LETO rats were used as control group (n=5). OLETF rats were aerobically trained 5 days/wk for 12 weeks at a speed of 15-21 m/min. After 48 hours the last training session, gastrocnemius muscle was removed and stored at -80°C for further analysis. RESULTS: As markers of oxidative stress, the levels of hydroperoxide and 4-HNE in OLETF groups were significantly higher compared with LETO group. There was no difference between Ex-OLETF and Sed-OLETF. Phosphorylation of IKK beta, IkB alpha, and cytosolic fraction of JNK was elevated in OLETF compared with LETO, however, there was no significant difference between Ex-OLETF and Sed-OLETF. The expression of HSP72 was downregulated in OLETF compared with LETO, but was significantly increased in Ex-OLETF compared with Sed-OLETF. NF-kB DNA binding activity in Sed-OLETF group was significantly higher compared with LETO group. Although it was not statistically significant, exercise training in Ex-OLETF group showed the trend of reducing the activation of NF-kB DNA binding activity compared with Sed-OLETF group. CONCLUSION: Our findings indicate that although oxidative stress, stress kinase activation, and lower HSP72 expression are found in OLETF skeletal muscle compared to LETO control, it appears that protective effect of exercise on type 2 diabetes would be regulated by independent of JNK and NF-kB pathway.