3-Thiomethyl-5,6-(dimethoxyphenyl)-1,2,4-triazine improves neurite outgrowth and modulates MAPK phosphorylation and HSPs expression in H2O2-exposed PC12 cells.

Abstract

Neurite outgrowth is an important aspect of neuronal plasticity and regeneration after neuronal injury. In this study we aimed to investigate the possible effect of 3-thiomethyl-5,6-dimethoxyphenyl-1,2,4-triazine (TDMT) on H(2)O(2)-induced impairment of neurite outgrowth. We found that TDMT could improve neurite outgrowth and neurite complexity in H(2)O(2)-exposed PC12 cells. Moreover, we found elevated levels of Hsp-70 and suppressed level of Hsp-90 in TDMT-treated cells in the presence of H(2)O(2). As another important signaling pathways that play role in neuritogenesis, as well as apoptosis, we measured the level of phosphorylated and total MAPKs proteins, JNK, ERK and p38 MAPK. We found that TDMT inhibits oxidative stress-induced phosphorylation of MAPKs. Since HSPs and MAPKs are both involved in coping with environmental changes, it will not be surprising if they can modify or augment each other's activity. Neuroprotective effect of this compound could represent a promising approach for treatment of neurodegenerative diseases.