Protective Effects Of MitoQ Against Hypoxia Injury And Impact On Autophagy

Objective:To study the protective effects of MitoQ against hypoxia injury and impact on autophagy on PC12 cell and rats.Methods:Observed cell morphology,measured cell viability,oxidative stress and energy metabolism indicators and the expression of apoptosis related proteins to study the protection effects of MitoQ in hypoxia PC12 cells.Researched the influence of MitoQ on autophagy in the condition of hypoxia by electron microscope and and measurement the expression of autophagy related proteins in PC12 cell.Simulate an altitude of 8000 m plateau hypoxia environment by used a large low pressure oxygen chamber.Then,We through observe histopathological slices,determining the level of oxidative stress and mitochondrial function as well as measurement apoptosis related proteins to study the anti-hypobaric hypoxia effects of MitoQ on rats.Researched the influence of MitoQ on autophagy under an altitude 8000 m plateau condition by electron microscope and measurement of autophagy related proteins.Results:Cell morphology after hypoxia is significant difference compared with normal group,cell volume decreased,pyknotic nucleus and adherent properties also weaken.The results of MTT showed hypoxia promote cell apoptosis,cell vialibity at hypoxia 24h and 48h was decreased by26.52%and 61.75%respectively compared to the model group.MitoQ can significantly improve the activity of PC12 cells in hypoxia,cell vialibity was increased by 24.81%in concentration of10^-88 M.At the same time,hypoxia increase LDH leakage,the level of intracellular ROS and lipid peroxidation,intracellular Ga²⁺overload and reduced the mitochondrial membrane potential of PC12 cell.Then,MitoQ significantly reduces LDH leakage,content of ROS,MDA,intracellular Ga²⁺,increase the mitochondrial membrane potential and decrease the expression level of Cytc and Bax to prevent PC12 cell from injury of hypoxia.Hypoxia induce PC12 cells autophagy,electron microscope observe more autophagosome compared with normal group and the expression of autophagy related proteins LC3?,Beclin1significant increased.The results also showed MitoQ reduce autophagy in PC12 cells under the condition of hypoxia and reduce the expression of autophagy related proteins.The results of simulation at an altitude of 8000 m plateau hypobaric hypoxia environment experiment shows hypoxia improve the level of lipid peroxidation,reduced activity of antioxidant enzymes SOD,induced intracellular calcium overload,decreasd the activity of mitochondrial respiratory chain complexes?,?,?,increased the expression of Cytc,Caspase3 and Bax of rat.Then,MitoQ reduce oxidative stress level,increase activity of antioxidant enzymes SOD,prevent calcium overload,improve mitochondrial function,rise mitochondrial membrane potential and increased the activity of mitochondrial respiratory chain complexes?,?,?,as well as,MitoQ decreased the expression level of Cytc,Caspase3 and Bax to play a protection role under the condition of hypobaric hypoxia on rats.The results of electron microscope and expression of LC3?,Beclin1 showed hypobaric hypoxia induce autophagy in rats.MitoQ significantly reduce the expression of autophagy related protein LC3?,Beclin1 in the condition of hypobaric hypoxia.Conclusion:The study in PC12 cells showed hypoxia cause cell apoptosis and MitoQ reduces LDH leakage,ROS,content of MDA,intracellular Ga²⁺,increase the mitochondrial membrane potential play a protection role in PC12 cell when hypoxia appear,at the same time,hypoxia induce autophagy and MitoQ inhibit autophagy of PC12 cells.Then,simulation at an altitude of8000 m plateau hypobaric hypoxia cause tissue damage.However,MitoQ increase activity of antioxidant enzymes,scavenging ROS,decrease the degree of lipid peroxidation,improve the activity of mitochondrial respiratory chain complexes to play a protective role in hypoxia rats and its mitochondrial function.Meanwhile,this induce autophagy on rats and MitoQ inhibit autophagy in rats under the condition of hypobaric hypoxia.This experiment research the effect of MitoQ on PC12 cell and rats under the condition of hypoxia and hypobaric hypoxia.The results showed MitoQ prevent the injury of oxidative stress damage and protect the function of mitochondria in hypoxia.Then,MitoQ suppress autophagy and we thought this effect maybe relation to the impact of MitoQ on scavenging ROS.