Objective: To observe the effect of methylmalonic acidemia on the apoptosis of cortical neurons and the c-jun N-terminal kinase (JNK), phosphorylation c-jun N-terminal kinase (p-JNK), c-fos, c-jun protein levels in cortical neuronal, and to explore the mechanism of brain damage induced by methylmalonic acidemia. Methods: The mouse cortical neuronal cells were cultured. The mouse cortical neuronal cells were induced by methylmalonic acidemia. Flow cytometry was used to detect the apoptosis of mouse cortical neurons. Neuron cells were divided into control group (added to normal medium), methylmalonic acidemia group (added to medium with methylmalonic acidemia concentration of 15 mmol·L-1) and JNK inhibitor group (added to medium with methylmalonic acidemia concentration of 15 mmol·L-1 and SP600125 concentration of 40 μmol·L-1).Western blotting was used to detect the protein levels of JNK, p-JNK, c-fos, c-jun, B-lymphoma-2 (Bcl-2), Bcl-2 related X protein (Bax), Caspase 3 and cleaved-caspase 3 in neurons. Results: Compared with the control group, when the concentration of methylmalonic acidemia were 5 mmol·L-1 and 10 mmol·L-1, the change of the proportion of apoptotic neurons was not obvious (P>0.05), when the concentration of methylmalonic acidemia was 15 mmol·L-1, the proportion of apoptotic neurons increased significantly (P<0.05). The relative expressions of p-JNK, c-fos and c-jun proteins in the neurons of methylmalonic acidemia group were higher than those in the control group (P<0.05). There was no significant difference in the relative expression of JNK protein between the methylmalonic acidemia group and the control group (P>0.05). The relative expressions of Bax,Caspase 3 and cleaved-caspase 3 protein in the methylmalonic acidemia group were higher than those in the control group (P<0.05). The relative expression of Bcl-2 protein in the methylmalonic acidemia group was lower than that in the control group (P<0.05). The relative expressions of Bax, Caspase 3 and cleaved-caspase 3 protein in the JNK inhibitor group were lower than those in the methylmalonic acidemia group (P<0.05), and the relative expression of Bcl-2 protein in the JNK inhibitor group was higher than that in the methylmalonic acidemia group (P<0.05). Conclusion: Methylmalonic acidemia can induce cell damage of mouse cortical neurons. The mechanism may be that methylmalonic acidemia can induce apoptosis of mouse cortical neurons by the JNK/MAPK pathway.
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