Effects Of Endurance Exercise On The Mitochondrial Oxdative Damage And Caspase-dependent Cell Apoptosis Of ICR Mice's Liver

With age, oxidative damage to mtDNA increase, which can lead to dysfunction of mitochondrial oxidative phosphorylation and reduce cellular energy metabolism, causing cell necrosis and apoptosis, so liver tissue with higher energy demand will subject to damage. It has be confirmed that endurance exercise can enhance antioxidant capacity by increasing the activity of antioxidant enzymes in the body,to reduce oxidative damage to mtDNA and apoptosis.The two main pathways of cell apoptosis are the Caspase dependent way and Caspase-independent way, but now the Caspase dependent apoptosis is still dominant, which is divided into two stages:activation period and implementation period. First,early cell death signal responses and activate the Starting Caspases; then,the Executive Caspases are activated,cell death process is running.Both starting and performing Caspase, usually are in the cytoplasm matrix in inactive zymogen form. Caspase plays a key role in the apoptosis pathway,especially of all the Caspase family members, Caspase-8 and Caspase-9 are the important Starting Caspases, Caspase-3 is the most important executors of apoptosis.Apoptosis is regulated strictly by apoptosis gene.Bcl-2 family members play a crucial role in the gene regulation of apoptosis process, such as Puma and Bax genes,which are very important to promote Apoptosis, PUMA protein with a BH3 domain, specifically located in the mitochondria in cells, can combinate Bcl-2, Bcl-xl through the BH3 domain.When the cell are stimulated by apoptosis,PUMA can translocate to the mitochondrial outer membrane, then the another important family member Bax will be activated, translocate into the mitochondrial outer membrane from the cytoplasm and promote the release of cytochrome C to induce apoptosis.Objective:To study the Effects of Endurance Exercise on the mitochondrial oxdative damage and Caspase-dependent cell apoptosis of ICR mice's Liver.Methods:32 mice were fed a week in the laboratory for adaptation, then 2 months old mice were randomly divided into two groups, control group(YC, n=8) and endurance training group (YE, n=8); 10 months old mice also were divided into two groups, control groups (OC, n=8) and endurance training group (OE, n=8). Endurance training group were trained for 4 weeks by 65%-75% of the maximum load endurance training (Qiao Shan treadmill is converted into animal treadmill), using incremental exercise test for different months. The training time is from18:00 to 19:00 on every evening except Sunday. After four weeks of training, all mice were killed by cervical. We can detect Liver mitochondrial ROS,mitochondrial membrane potential,liver Caspase-3, Caspase-8 and Caspase-9 activity with the microplate; also can use the method of ELISA to discover the content of the liver 8-OH-dG; liver Puma, Bax gene transcription level can be detected using real-time fluorescence quantitative PCR.Results:â‘ Compared with the control groups of 2 months and 10 months, endurance exercise increased membrane potential and ROS of liver mitochondrial significantly, but the content of 8-OH-dG was significantly decreased. Besides, for the control group of 2 months, Liver 8-OH-dG of 10-month-old control group was significantly increased.â‘¡Endurance exercise significantly reduced the activity of liver Caspase-3, Caspase-8, Caspase-9 compared to the two control groups.â‘¢Endurance exercise significantly reduced the Puma and Bax gene transcription level of mice's liver aged 2 months, but significantly increased their level of 10 months mice's liver.Conclusions:(1) Endurance exercise can significantly reduce the oxidative damage of mouse liver mtDNA with age. (2)After endurance exercise, the transcription level of different months mice's liver gene are inconsistent, but their apoptotic starting and executive Caspases'activity of the liver were both inhibited significantly to reduce apoptosis. (3) After endurance exercise, there are some relationships between the inhibition of apoptosis in the liver and mitochondrial DNA oxidative damage in the liver.