Ketamine Enhances The Ability Of Antioxidative Stress Through Regulating The Expression Of KAT6B In The Central Nervous System

Background and Objective: Recent studies indicated that the rapid antidepressant effect of ketamine was related to anti-inflammatory action in central nervous system(CNS),and the increase of expression of acetylation could enhance the activities of antioxidant kinases,however,the mechanism was not clear.Acetylation was regulated by acetyltransferases,lysine acetyltransferase 6B(KAT6B),which was encoded by KAT6 B gene,was included.Studies suggested that circRNAs and linear RNAs existed competitive relationship.Therefore,the main purpose of our research was to investigate the effects of ketamine on the KAT6 B circRNA and KAT6 B linear RNA for revealing a new mechanism of ketamine's antioxidant stress effect.Methods: Firstly,the activities of antioxidant enzymes in astrocytes were evaluated after ketamine treatment,including glutathione peroxidase(GSH-Px),total superoxide dismutase(T-SOD)and catalase(CAT).Then,the expression levels of nuclear factor erythroid 2-related factor 2(Nrf2),acetylation,KAT6 B protein,KAT6 B mRNA and KAT6 B circRNA in astrocytes and hippocampus were detected after astrocytes and SD rats were treated with ketamine.Finally,the activities of antioxidant enzymes and the expressive levels of Nrf2 protein and acetylation were evaluated after inhibiting the expression of KAT6 B mRNA of astrocytes.Results: The antioxidant enzymes activities,including GSH-Px,T-SOD and CAT,were significantly increased after ketamine treatment(p<0.05).The expressive levels of Nrf2 protein,acetylation and KAT6 B mRNA were significantly increased after ketamine treatment in astrocytes and hippocampus(p<0.05),but KAT6 B circRNAs levels were obviously decreased(p<0.05).After inhibiting the expression of KAT6 B mRNA,the antioxidant enzymes' activities,Nrf2 and acetylation levles in astrocytes were significantly decreased after ketamine treatment(p<0.05).Conclusion: Ketamine increases the ability of antioxidative stress of CNS through regulating the expression of KAT6 B gene,the mechanisms were related to decreasing the expression of KAT6 B circRNAs and enhancing the expression of KAT6 B mRNAs.