Attenuation of Magnesium Sulfate on CoCl2-Induced Cell Death by Activating ERK1/2/MAPK and Inhibiting HIF-l alpha via Mitochondrial Apoptotic Signaling Suppression in a Neuronal Cell Line

作者：Huang Chih Yang; Hsieh You Liang; Ju Da Tong; Lin Chien Chung; Kuo Chia Hua; Liou Yi Fan; Ho Tsung Jung; Tsai Chang Hai; Tsai Fuu Jen; Lin Jing Ying^*

来源：Chinese Journal of Physiology, 2015, 58(4): 244-253.

DOI：10.4077/CJP.2015.BAD296

• apoptosis
• Bc1-2 family
• CoCl2
• ERK1/2
• MgSO4
• mitochondria

Magnesium sulfate (MgSO4) ameliorates hypoxia/ischemia-induced neuronal apoptosis in a rat model. This study aimed to investigate the mechanisms governing the anti-apoptotic effect of MgSO4 on cobalt chloride (CoCl2)-exposed NB41A3 mouse neuroblastoma cells. MgSO4 increased the viability of NB41A3 cells treated with CoCl2 in a dose-dependent manner. MgSO4 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. MgSO4 also attenuated the CoCl2-induced disruption of mitochondrial membrane potential (Delta Psi(m)) and reduced the release of cytochrome c form the mitochondria to the cytosol. Furthermore, exposure to CoCl2 caused activation of the hypoxia-inducible factor la (HIF-1 alpha). On the other hand, MgSO4 markedly reduced CoCl2-induced HIF-l alpha activation and suppressed HIF-la downstream protein BNIP3. MgSO4 treatment induced ERK1/2 activation and attenuated CoCl2-induced activation of p38 and JNK. Addition of the ERK1/2 inhibitor U0126 significantly reduced the ability of MgSO4 to protect neurons from CoCl2-induced mitochondrial apoptotic events. However, incubation of cultures with the p38 and JNK inhibitors did not significantly affect MgSO4-mediated neuroprotection. MgSO4 appears to suppress CoCl2-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.

• 出版日期2015-8-31
• 单位中国医科大学