Egzersizle İndüklenen Hsp72’nin Glukokortikoid Kaynaklı İskelet Kası Atrofisini Önlemesindeki Rolü

Abstract

Many physiological and pathological conditions or drugs used for the treatment of diseases cause skeletal muscle atrophy. Glucocorticoids are widely used exogenously in treating many diseases due to their immunosuppressive and anti-inflammatory properties and are the primary cause of drug-induced muscle atrophy. It is very well known that exercise prevents skeletal muscle atrophy, and glucocorticoid-induced muscle atrophy is not an exception. One of the changes that occur in the organism due to aerobic exercises is the elevation of body temperature. It has been known that the body temperature increases a few degrees rapidly as a consequence of heat stress and induces a group of proteins in the cell called heat shock proteins. Notably, the increase in Hsp72 plays a critical role in maintaining cellular homeostasis and preventing skeletal muscle atrophy. Therefore, exercise plays a crucial role in various intracellular signaling pathways due to increased contraction and metabolic activity. However, it is remarkably essential to investigate the mechanisms in muscle cells activated by exercise and protect skeletal muscle from glucocorticoid-induced muscle atrophy.This study was designed to elucidate whether exercise protects against glucocorticoid-induced skeletal muscle atrophy in an Hsp72 dependent manner. To this end, 3-4 month female Sprague Dawley rats were divided in to following study groups: control (C), dexamethasone (D), warm exercise (WE), warm exercise and dexamethasone (WED), cold exercise (CE), and cold exercise and dexamethasone (CED) (n = 8). The rats in the exercise groups were given a 10-day running exercise gradually increasing the speed and duration of 30m/min 60min/day from the 5th day. Dexamethasone was injected subcutaneously at a dose of 1mg /kg /day for 5 days to D, CED, and NED groups. Skeletal muscle atrophy muscle was determined by dividing plantaris weight by the initial body weight, and the levels of Hsp72, p-Akt, Akt, and p-FoxO3 were determined by Western Blot. D groups plantaris muscle weight decreased significantly compared to the C group (p <0.05), while the muscle weights of the CED, and WED groups were higher than the D group (p <0.05), while only the WED group was not different from the K group (p > 0.05). Hsp72 levels of the WE and WED groups were significantly increased compared to the C group (p <0.05). Compared with the C group, the p-Akt levels of the D, CED and WED groups decreased significantly, while the p-Akt levels of the WED group were significantly higher than both the D and CED groups (p <0.05). Finally, when the p-FoxO3 levels of the groups were compared, it was seen that only the WED group was significantly higher than the D group (p <0.05). As a result, both exercising groups with dexamethasone injection (CED and WED) attenuated plantaris muscle atrophy (p<0,05). On the other hand, while there was no significant difference between control and WED groups (p>0,05), plantaris muscle weight of group CED was significantly lower than control (p<0,05). These results indicate that elevated body temperature plays a role in preventing glucocorticoid-induced skeletal muscle atrophy through the expression of Hsp72 during exercise.