AIMP1 exerts hearing protection role in age related hearing loss mice by regulating SIRT1 expression.

BACKGROUND: Age related hearing loss (ARHL) is a sensorineural hearing disease caused by multiple factors and its pathogenesis is still unclear. This work aims to investigate the precise role of AIMP1 in ARHL. METHODS: HEI-OC1 cells were treated with 1 mM H(2)O(2) for 2 h to induce cell damage. CCK-8, flow cytometry and TUNEL staining examined cell viability and apoptosis. DCFH-DA fluorescence probe assessed ROS. The levels of MDA, SOD and copper were detected by kits. The expression of proteins related to mitophagy, cuproptosis were examined by western blotting and immunofluorescence. Finally, D-galactose was administered to mice to establish an ARHL model for verifying the functional role of AIMP1 in ARHL. RESULTS: AIMP1 and SIRT1 were down-regulated in H(2)O(2)-treated HEI-OC1 cells. AIMP1 overexpression promoted cell viability, reduced ROS and MDA levels, and increased SOD levels in H(2)O(2)-treated HEI-OC1 cells. Moreover, the levels of copper and apoptosis were decreased in H(2)O(2)-treated HEI-OC1 cells in the presence of AIMP1 overexpression. AIMP1 overexpression caused a down-regulation of cuproptosis-related proteins FDX1, DLAT, DLST, and an up-regulation of mitophagy-related proteins PINK1, Parkin, Mfn2 and Drp1 in H(2)O(2)-treated HEI-OC1 cells. Knockdown PINK1 or SIRT1 reversed the influence of AIMP1 overexpression on H(2)O(2) induced HEI-OC1 cell damage. In vivo, AIMP1 overexpression reduced damage of cochlear tissues and partially restored hearing in ARHL mice. CONCLUSION: AIMP1 up-regulated SIRT1 to promote PINK1/Parkin-mediated mitophagy and inhibit cuproptosis of cochlear hair cells in ARHL mice. Thus, AIMP1 may be a potential target for ARHL treatment.