Attenuation of magnesium sulfate on CoCl₂-induced cell death by activating ERK1/2/MAPK and inhibiting HIF-1α via mitochondrial apoptotic signaling suppression in a neuronal cell line

Magnesium sulfate (MgSO ₄ ) ameliorates hypoxia/ischemia-induced neuronal apoptosis in a rat model. This study aimed to investigate the mechanisms governing the anti-apoptotic effect of MgSO ₄ on cobalt chloride (CoCl ₂ )-exposed NB41A3 mouse neuroblastoma cells. MgSO ₄ increased the viability of NB41A3 cells treated with CoCl ₂ in a dose-dependent manner. MgSO ₄ treatment was shown to lead to an increase in the anti-apoptotic Bcl-2 family proteins, with a concomitant decrease in the pro-apoptotic proteins. MgSO ₄ also attenuated the CoCl ₂ -induced disruption of mitochondrial membrane potential (ΔΨm) and reduced the release of cytochrome c form the mitochondria to the cytosol. Furthermore, exposure to CoCl ₂ caused activation of the hypoxia-inducible factor 1α (HIF-1α). On the other hand, MgSO ₄ markedly reduced CoCl ₂ -induced HIF-1α activation and suppressed HIF-1α downstream protein BNIP3. MgSO ₄ treatment induced ERK1/2 activation and attenuated CoCl ₂ -induced activation of p38 and JNK. Addition of the ERK1/2 inhibitor U0126 significantly reduced the ability of MgSO ₄ to protect neurons from CoCl ₂ -induced mitochondrial apoptotic events. However, incubation of cultures with the p38 and JNK inhibitors did not significantly affect MgSO ₄ -mediated neuroprotection. MgSO ₄ appears to suppress CoCl ₂ -induced NB41A3 cell death by activating ERK1/2/ MAPK pathways, which further modulates the role of Bcl-2 family proteins and mitochondria in NB41A3 cells. Our data suggest that MgSO ₄ may act as a survival factor that preserves mitochondrial integrity and inhibits apoptotic pathways. Copyright © 2015 by The Chinese Physiological Society and Airiti Press Inc.