OBJECTIVE: Lithium and valproic acid (VPA) have been reported to produce antioxidant effects by increasing the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) expression, which may contribute to their neuroprotective properties. As a coactivator for many transcriptional factors including PGC-1α, coactivator-associated arginine methyltransferase1(CARM1) regulates oxidative metabolism and mitochondrial biogenesis. Besides, Sirtuin3 (SIRT3), a new target of PGC-1α, plays an important role in preserving mitochondrial function.
RESULTS: Here we found that protein levels of SIRT3 and CARM1 were decreased during oxidative stress in motor neuronal cells (NSC34). Pretreatment of NSC34 cells with lithium (5 mmol/L), VPA (1 mmol/L), or lithium plus VPA for 24 hours, significantly reduced hydrogen peroxide (H2O2)-induced cytotoxicity, and increased SIRT3 and CARM1 levels.
CONCLUSION: Our results suggest that lithium and VPA may decrease vulnerability of motor neuronal cells to cellular injury evoked by oxidative stress, which possibly arising from putative mitochondrial disturbances. And further study of the molecular mechanisms of SIRT3 and CARM1 regulation may provide a novel target for treating motor neuron disease.