Abstract

Traumatic brain injury (TBI) is a type of brain disease that causes disability and a high mortality rate, affecting patient health. Our study aimed to explore the mechanism of F-box protein 10 (FBXO10) in neuronal apoptosis and Golgi stress. Cell viability was detected by cell counting kit-8 (CCK-8). Lactate dehydrogenase (LDH), interleukin-1β (IL-1β), and tumor necrosis factor-alpha (TNF-α) levels were measured by commercial kit or enzyme linked immunosorbent assay (ELISA). Apoptosis was assayed by flow cytometry. Immunofluorescence and Western blot were used to detect Rat sarcoma (RAS), total-Extracellular signal-regulated kinase (ERK)1/2, phospho-ERK1/2, and Golgi stress marker proteins (GM130, GOLPH3, and Golgin97) expression. The FBXO10-RAS interaction and RAS ubiquitination were assessed by co-immunoprecipitation. Trimethylation of Lys-27 in histone 3 (H3K27me3) modification level on FBXO10 promoter was analyzed by chromatin immunoprecipitation (ChIP). Knockdown of RAS suppressed Golgi stress and apoptosis in H 2 O 2 -treated HT-22 and NSC34 cells by inactivating the RAS/ERK axis. FBXO10 suppressed Golgi stress and apoptosis in H 2 O 2 -induced neuronal cells. Furthermore, FBXO10 inhibited Golgi stress and apoptosis by inactivating the RAS/ERK axis. Mechanistically, the upregulated enhancer of zeste homolog 2 (EZH2) repressed FBXO10 expression by promoting H3K27me3 modification in the FBXO10 promoter region, and FBXO10 promoted the degradation of RAS in an ubiquitin-dependent manner. Moreover, EZH2 activated the RAS/ERK axis by downregulating FBXO10 expression to promote Golgi stress and apoptosis in H 2 O 2 -treated HT-22 and NSC34 cells. EZH2-mediated H3K27me3 modification promoted Golgi stress and apoptosis in neuronal by activating the RAS/ERK axis via inhibition of FBXO10 expression. Our study provided the theoretical basis and potential clinical targets for TBI treatment. Graphical EZH2-mediated H3K27me3 modification inhibits FBXO10 expression, which a