| Background:Skeletal muscle accounts for 40-45% of body weight and plays a crucial role in the body’s daily life,metabolism and other physiological functions.Aging leads to decreased muscle mass and loss of function,resulting in impaired mobility and reduced quality of life.Therefore,it is very important to maintain or increase the quality and function of skeletal muscle throughout life,and exercise is beneficial to increase muscle protein synthesis and improve muscle content,which is one of the important means to maintain and improve physiological and metabolic health.Studies have shown that the skeleton protein Filamin C is closely related to the protein BAG3.In addition,BAG3 can also promote protein synthesis and activation of skeletal muscle satellite cells,promoting skeletal muscle hypertrophy.BAG3 promotes the autophagy degradation of Filamin C in mechanical damage,reduces the impact of damaged proteins on the body,and alleviates skeletal muscle attenuation caused by aging.However,whether exercise promotes muscle protein synthesis and degradation through the Filamin C-BAG3 mechanical sensor remains to be further explored.Objective:The purpose of this study is to explore the relationship between Filamin C-BAG3 mechanical sensor and mTOR signal pathway and chaperone-assisted selective autophagy(chaperone-assisted selective autophagy,CASA),and to further explore the role and molecular mechanism of Filamin C-BAG3 mechanical sensor in the process of exercise promoting protein synthesis and protein degradation,and to further compare the exercise effects of resistance exercise and treadmill exercise,so as to provide new research ideas for the construction of skeletal muscle cytoskeleton.It can also provide alternative exercise therapy for skeletal muscle decline.Methods:In the experiment,C57/L6 mice were divided into three groups: quiet control group,resistance training group and treadmill exercise group,with 8 mice in each group.Mice in the exercise group exercised on Monday,Wednesday and Friday every week,and the control group was fasted and abstained from water during the training.Grasp strength of mice was measured before formal training and after the last week of training.Each Sunday the experimenter was required to measure the body weight of mice in each group and the maximum load-bearing capacity(Max value)of mice in group R.Eight weeks after the experiment was conducted,the samples were collected.The changes of quadriceps femoris in mice were detected by Hematoxylin-eosin staining.Western blotting and Wes were used to detect the protein levels of Filamin C,BAG3,TSC1,mTOR,4E-BP1,SYNPO2,HSC70 and LAMP2 a in the quadriceps femoris of mice.We use IBM SPSS STATISTICS 23 to analyze the data.And the experimental data was graphed by Graph Pad Prism8.Results:(1)The changes of body weight,wet weight ratio of muscle and cross-sectional area of quadriceps femoris muscle fibers: Compared with the first week of the experiment,the body weight of mice in group C increased in the eighth week(P<0.05),and there was no statistical difference in body weight between group R and group A)(P>0.05).Compared with the control group,the wet weight/body weight ratio of quadriceps femoris muscle in resistance training group was significantly increased(P<0.05),and there was no significant difference between the treadmill exercise group and the control group(P>0.05).(2)Indicator changes related to Filamin C-BAG3 mechanical sensor: protein expressions of Filamin C,BAG3 and p-BAG3 in the quadriceps femoris of aging mice were detected by Western blotting.The results showed that the expression of Filamin C protein in group R was significantly increased compared with that in group C(P<0.05),and the expression of Filamin C protein in group A tended to be higher than that in control group,but there was no significant difference(P>0.05).There was no significant difference in the protein level of BAG3 in the quadriceps femoris of mice among all groups(P > 0.05).Compared with group C,the ratio of P-BAG3 /BAG3 in the quadriceps femoris of mice in group R tended to increase(P > 0.05),the protein level of P-BAG3 and the ratio of P-BAG3 / BAG3 in the quadriceps femoris of mice in group A were higher than those in group C(P<0.05).(3)Indicator changes related to protein synthesis: protein expressions of TSC1,mTOR and 4EBP1 in the quadriceps femoris of aging mice were measured by Western blotting.The consequence showed as follows: the protein level of TSC1 in the quadriceps femoris of mice in two exercise groups(groups R and A)was higher than that in group C(P<0.05);The protein levels of mTOR and 4EBP1 in the quadriceps femoris of mice in group R were higher than those in group C(P<0.05),and there was no significant difference in the protein levels of mTOR and 4EBP1 in group A and group C.(4)Index changes related to protein degradation: Western blotting was used to detect the protein expressions of SYNPO2,HSC70 and LAMP2 a in the quadriceps femoris of aging mice.The results showed that the protein level of SYNPO2 in the quadriceps femoral muscle of mice in the group R was lower than that in the group C,and the protein expression level in the group A was higher than that in the group C,but from A statistical point of view,there was no statistical difference in the data of this group(P<0.05).The expression of HSC70 protein in skeletal muscle of mice in exercise group(group R,group A)was increased,but no significant difference was found.The expression of LAMP2 a protein in group A was higher than that in group C and R(P<0.05).Conclusion :(1)Resistance exercise training can effectively increase the ratio of wet weight to body weight of quadriceps femoris,improve the relative grip strength of mice limbs.(2)Resistance exercise may activate mTOR pathway and promote protein synthesis by sensing tension through the Filamin C-BAG3 mechanical sensor.(3)Aerobic exercise may perceive tension through the Filamin C-BAG3 mechanical sensor,form autophagosomes,activate CASA,degrade proteins. |
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