Greater Protective Potent of s-Methyl Cysteine and Syringic Acid Combination for NGF-differentiated PC12 Cells against Kainic acid-induced Injury

Objective: The effects of pre-treatments from s-methyl cysteine (SMC) alone, syringic acid (SA) alone and SMC plus SA against kainic acid (KA) induced injury in nerve growth factor (NGF) differentiated PC12 cells were investigated. Methods: NGF-differentiated PC12 cells were treated with 1 μM SMC, 1 μM SA or 0.5 μM SMC plus 0.5 μM SA for 2 days. Subsequently, cells were further treated by 150 μM KA. Results: KA suppressed Bcl-2 mRNA expression, enhanced Bax mRNA expression and casued cell death. SMC was greater than SA, and similar as SMC+SA in increasing Bcl-2 mRNA expression. SMC+SA led to greater increase in mitochondrial membrane potential and cell survival than SMC or SA alone. SMC+SA resulted in more reduction in reactive oxygen species and tumor necrosis factor-alpha generation, more increase in glutathione content and glutathione reductase activity than SMC or SA alone. KA up-regulated protein expression of nuclear factor kappa B (NF-κB) p65 and phosphorylated p38 (p-p38). SMC or SA pre-treatments alone limited protein expression of both factors. SMC+SA resulted in more suppression in NF-κB p65 and p-p38 expression. KA decreased glutamine level, increased glutamate level and stimulated calcium release. SMC pre-treatments alone reversed these alterations. SMC alone elevated glutamine synthetase (GS) activity and mRNA expression. SMC+SA led to greater GS activity and mRNA expression than SMC pre-treatments alone. Conclusion: These findings suggested that this combination, SMC+SA, might provide greater protective potent for neuronal cells.