The protective role of mesencephalic astrocyte-derived neurotrophic factor in endoplasmic reticulum stress in RT4-D6P2T schwannoma sells with the S63del MPZ mutation

Background: Endoplasmic reticulum stress (ERS) occurred in S63del mutant CMT1B mice model, and few drugs has been studied. Mesencephalic astrocyte-derived neurotrophic factor (MANE) can inhibit ERS. This study aimed at investigating the effect of MANE on ERS of RT4-D6P2T schwannoma cells with S63del MPZ Mutation. Methods: Experimental grouping: blank control group, blank control + MANE group, lentivirus group, lentivirus + MANE group, S63del MPZ group, S63del MPZ + MANE group. CCK8 and Annexin-EITC/PI were used to detect cell proliferation and apoptosis. JC-1 was used to detect Delta Psi m. MANE GRP78 and CHOP mRNA and protein were detected by using RT-qPCR, western blotting and immunofluorescence. ER-Tracker and mito-tracker were used to observe the morphology of endoplasmic reticulum (ER) and mitochondria. Results: Cell proliferation decreased (p < 0.001) and apoptosis increased (p < 0.001) in S63del MPZ group: cell proliferation increased (p = 0.005) and apoptosis decreased (p < 0.001) in S63del MPZ + MANF group. Delta Psi m decreased (p < 0.001), MAW GRP78, CHOP, ATF6, P-PERK/PERK, P-IRE1/IRE1, Bax and Caspase3 increased (p < 0.001) and Bc12 decreased (p < 0.001) in S63del MPZ group. MANF, GRP78, CHOP, ATF6, P-PERK/PERK, P-IREVIRE1, Bax and Caspase3 decreased (p < 0.001) and Bcl2 increased (p < 0.001) in S63del MPZ group. Conclusions: ERS occurred in RT4-D6P2T cells with S63del MPZ mutation, and MANE exerted protective effect in RT4-D6P2T cells with S63del MPZ mutation.