Abstract
Endoplasmic reticulum stress (ERS) occurred in S63del mutant CMT1B mice model, and few drugs has been studied. Mesencephalic astrocyte-derived neurotrophic factor (MANF) can inhibit ERS. This study aimed at investigating the effect of MANF on ERS of RT4-D6P2T schwannoma cells with S63del MPZ Mutation. Experimental grouping: blank control group, blank control + MANF group, lentivirus group, lentivirus + MANF group, S63del MPZ group, S63del MPZ + MANF group. CCK8 and Annexin-FITC/PI were used to detect cell proliferation and apoptosis. JC-1 was used to detect ΔΨm. MANF, 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. 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. ΔΨm decreased (p < 0.001), MANF, GRP78, CHOP, ATF6, P-PERK/PERK, P-IRE1/IRE1, Bax and Caspase3 increased (p < 0.001) and Bcl2 decreased (p < 0.001) in S63del MPZ group. MANF, GRP78, CHOP, ATF6, P-PERK/PERK, P-IRE1/IRE1, Bax and Caspase3 decreased (p < 0.001) and Bcl2 increased (p < 0.001) in S63del MPZ group. ERS occurred in RT4-D6P2T cells with S63del MPZ mutation, and MANF exerted protective effect in RT4-D6P2T cells with S63del MPZ mutation.
Highlights
Charcot-Marie-Tooth disease (CMT) is the most common hereditary peripheral neuropathy [1]
We found that Endoplasmic reticulum stress (ERS) occurred in RT4D6P2T schwannoma cells with the S63del myelin protein zero (MPZ) mutation and Mesencephalic astrocyte-derived neurotrophic factor (MANF) played a protective role against ERS associated RT4-D6P2T schwannoma cells with the S63del MPZ mutation
After 24 hours of culture, the RT4-D6P2T schwannoma cells in each group completely adhered to the wall, and the cells stretched out pseudopods, showing irregular shapes
Summary
Charcot-Marie-Tooth disease (CMT) is the most common hereditary peripheral neuropathy [1]. CMT1B, caused by myelin protein zero (MPZ) mutations, is the second most common type of CMT1 [3,4]. More than 200 MPZ mutations have been detected [5], of which the S63del and R98C MPZ mutations have been used to study the pathogenesis of CMT1B [6,7,8]. Endoplasmic reticulum stress (ERS) occurred in S63del mutant CMT1B mice model, and few drugs has been studied. This study aimed at investigating the effect of MANF on ERS of RT4-D6P2T schwannoma cells with S63del MPZ Mutation. ∆Ψm decreased (p < 0.001), MANF, GRP78, CHOP, ATF6, P-PERK/PERK, P-IRE1/IRE1, Bax and Caspase increased (p < 0.001) and Bcl decreased (p < 0.001) in S63del MPZ group. MANF, GRP78, CHOP, ATF6, P-PERK/PERK, P-IRE1/IRE1, Bax and Caspase decreased (p < 0.001) and Bcl increased (p < 0.001) in S63del MPZ group. Conclusions: ERS occurred in RT4-D6P2T cells with S63del MPZ mutation, and MANF exerted protective effect in RT4-D6P2T cells with S63del MPZ mutation
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