Objective: To observe the effect of the methylmalonic acid on mouse cortical neurons and cells protein isoaspartate methyltransferase 1(PCMT1)/mammalian sterile line 20-like kinase 1(MST1) pathway in brain injury caused by methylmalonic acid. Methods: The mouse cortical neurons were cultured. Methylmalonic acid with different concentrations induced mouse cortical neuronal cells and the changes of cell morphology were observed.MTT assay was used to detect the activity of cortical neurons in mice. The protein levels of PCMT1, MST1, cl-MST1, p-MST1, Caspase-3, B-cell lymphoma-2 (Bcl-2), and Bcl-2 related X protein (Bax) were detected by Western blotting. Results: After 24 hours of induction with different concentrations of methylmalonic acid, it was observed under microscope that the morphology of neurons did not change significantly when the concentration of methylmalonic acid ≤ 8 mmol·L-1, but vacuoles appeared in the neurons when the concentration of methylmalonic acid was 12 mmol·L-1, and the neurite processes were shortened. The cell body shrinked; When the concentration of methylmalonic acid was 16 mmol·L-1, the neuron body fell off and almost all the processes were broken, and methylmalonic acid significantly decreased the activity of neuron cells. The relative expression of PCMT1, MST1 protein in methylmalonic acid group was lower than those in control group and CGP3466B group (all P<0.05), and the expression of cl-MST1,p-MST1 protein was higher than those in the control group and the CGP3466B group (all P<0.05). The expression of Caspase-3 and Bax protein in methylmalonic acid group was higher than those in the control group and the CGP3466B group (all P<0.05), and the expression of Bcl-2 protein was lower than that in the control group and the CGP3466B group (P<0.05).Conclusion: Methylmalonic acid can induce apoptosis in cortical neurons. The mechanism may be that methylmalonic acid induces neuronal apoptosis through the PCMT1/MST1 pathway.
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