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Attenuation of Magnesium Sulfate on CoCl_2-Induced Cell Death by Activating ERK1/2/MAPK and Inhibiting HIF-1α via Mitochondrial Apoptotic Signaling Suppression in a Neuronal Cell Line
並列摘要
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 MgSO4 may act as a survival factor that preserves mitochondrial integrity and inhibits apoptotic pathways.
延伸閱讀
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