Salsolinol, an endogenous neurotoxin, activates JNK and NF-κB signaling pathways in human neuroblastoma cells

Salsolinol, an endogenous neurotoxin, is known to be involved in the pathogenesis of Parkinson's disease (PD). In the present study, we have investigated the effects of salsolinol on the activation of two different signaling pathways that involve c-Jun N-terminal kinase (JNK), and nuclear factor-kappa B, (NF-kappa B) in human dopaminergic neuroblastoma SH-SY5Y cells. Salsolinol treatment caused upregulation in the levels of c-Jun and phosphorylated c-Jun. It also caused degradation of I kappa B alpha and translocated the active NF-kappa B into the nucleus. The binding activity of NF-kappa B to DNA was enhanced by salsolinol in a concentration dependent manner. Furthermore, salsolinol decreased the levels of the anti-apoptotic protein Bcl-2, and increased pro-apoptotic protein Bax, while enhancing the release of cytochrome-c from mitochondria. Mitochondrial complex-I activity was significantly decreased and reactive oxygen species (ROS) were increased in salsolinol treated cells. These results partly suggest that salsolinol-induced JNK and NF-kappa B signaling pathways may be involved in induction of apoptosis in human dopaminergic neurons, as seen in Parkinson's disease.