The Protective Effect Of DhHP-6 On Mitochondrial Oxidative Damage In C.elegans

Oxidative damage is caused by the imbalance between the production and elimination of reactive oxygen species in tissues and cells.Accumulation of oxidative damage will damage the health of the body through inducing cancer,cardiovascular disease,neurodegenerative diseases,liver diseases,respiratory diseases,rheumatoid arthritis,reproductive systems diseases and other diseases.As the main site of ROS production,mitochondria has broad application prospects as antioxidant pressure target.The model animals currently used for anti-oxidative stress research are rats,mice,star sturgeon,brine shrimp,Holstein young bull,and C.elegans.As a mature model organism,C.elegans is widely used in oxidative damage.Dh HP-6 is a small molecule peptide synthesized that our laboratory based on the simulation of natural microperoxidase by solid phase peptide synthesis.To investigate the protective effect of Dh HP-6 on mitochondrial oxidative damage in C.elegans,we selected mitochondrial toxic agent PQ as the inducer of mitochondrial oxidative damage to construct the mitochondrial oxidative damage model of C.elegans,which can induce mitochondrial oxidative damage in C.elegans.The index was used to evaluate the protective effect of Dh HP-6 on mitochondrial oxidative damage in C.elegans.Firstly,we explored the optimal induction dose of PQ induced mitochondrial oxidative damage in C.elegans and the optimal concentration of Dh HP-6.The experimental results showed that the optimum PQ induced concentration of mitochondrial oxidative damage in C.elegans was 10 Mm and the best Dh HP-6 feeded concentration was 100 ?M.Then,we further tested the production of ROS,mitochondrial membrane potential changes and the expression of mitochondrial dynamics related genes of the group of 10 m M PQ induced,the group of 10 m M PQ induced accompanying 100 ?M Dh HP-6 and the group of control(no induction,no administration)of C.elegans.The experimental results show that 100 ?M Dh HP-6 could reduce the increase of ROS induced by 10 m M PQ,increase the mitochondrial membrane potential induced after 10 m M PQ induction,and restore the expression of genes of mitochondrial dynamics induced by 10 m M PQ.Therefore,we conclude that 100 ?M Dh HP-6 has protective effect on C.elegans which mitochondria is damaged by 10 m M PQ induced.To further understand which genes Dh HP-6 acting and related with mitochondrial after PQ inducing in C.elegans,three groups of C.elegans were tested for RNAseq at 36 hours after PQ induction.The sequencing results showed that genes that Dh HP-6 acting after PQ induction and related with mitochondrial of C.elegans are mainly concentrated in restoring reproductive stress pathway.Because reproductive stress was also an injury caused by oxidative damage,it can be concluded that Dh HP-6 can alleviate the oxidative damage of C.elegans in some cases.The results showed that Dh HP-6 could strongly prolong the lifespan of C.elegans induced by 10 m M PQ,and reduce the production of ROS which will increased after PQ induction in C.elegans,and increase the membrane potential which will reduce after PQ induction in C.elegans and restore the expression of disordered mitochondrial dynamics related genes which can generate the reproductive stress caused by PQ induction.All symptoms caused by PQ induction are all manifestations of oxidative damage.Therefore,we conclude that Dh HP-6 can protect C.elegans against of mitochondrial oxidative stress induced by PQ,in some extent.