Tripartite motif 72 inhibits apoptosis and mitochondrial dysfunction in neural stem cells induced by anesthetic sevoflurane by activating PI3K/AKT pathway.

Abstract

Anesthetics exposure induces neurocognitive deficits during brain development and impairs self-renewal and differentiation of neural stem cells (NSCs). Tripartite motif 72 (TRIM72, also known as mitsugumin 53, MG53) is involved in tissue repair and plasma membrane damage repair. The neuroprotective effect of TRIM72 against sevoflurane-induced neurotoxicity of NSCs was investigated in this study. First, human NSCs were exposed to different concentrations of sevoflurane. Results showed that TRIM72 was downregulated in sevoflurane-treated NSCs. Exposure to sevoflurane reduced cell viability in NSCs. Second, sevoflurane-treated NSCs were stimulated with recombinant human TRIM72 (rhTRIM72). Treatment with rhTRIM72 enhanced the cell viability in sevoflurane-treated NSCs. Moreover, treatment with a rhTRIM72-attenuated sevoflurane-induced increase in caspase-3 activity in NSCs. Third, JC-1 aggregates were deceased and JC-1 monomer was increased in sevoflurane-treated NSCs, which were reversed by rhTRIM72. Furthermore, rhTRIM72 also weakened sevoflurane-induced decrease in superoxide dismutase and glutathione peroxidase and increase in malondialdehyde and reactive oxygen species in NSCs. Finally, reduced phosphorylation levels of protein kinase B (AKT) and phosphatidylinositol 3-kinase (PI3K) in sevoflurane-treated NSCs were upregulated by rhTRIM72. In conclusion, TRIM72 inhibited cell apoptosis and reduced the mitochondria membrane potential of sevoflurane-treated NSCs through activation of the PI3K/AKT pathway.