Molecular Mechanisms Of Thioredoxin And CDK5 Expression Induced By KC1

Parkinson's disease is a common neurodegenerative disease. Its clinical manifestation includes tremor, rigidity and hypokinesia. The pathology is progressive denaturalization, necrosis and decrease of dopaminergic cells in substantia nigra. Therefore, protection of neuronal cells is important for treating this disease.Potassium chloride (KCl) changes the permeability of cell membrane ion channels, induces membrane depolarization, regulates Ca2+ channels of plasma membrane and calcium base membrane, causes increase of intracellular free Ca2+ concentration. KCl has the roles in exciting cells, promoting neuronal growthl and protecting neurons.Thioredoxin(Trx) is a multifunction protein of 12KDa, exists in the prokaryotes and eukaryotes. It consists the Trx system together with the NAPDH and thioredoxin reductase, with conserved redox active cite:-Cys-Gly-Pro-Cys-. It has many biological functions, including anti-oxidation, inhibiting apoptosis, regulating transcription factor activity and so on. Increasing evidences demonstrate that Trx is closely related to human diseases, Trx protects neurons, and plays an important role in the development process of neurodegenerative diseases.Cyclin-dependent kinase 5 (CDK5) is a proline-dependent serine/threonine protein kinase. Its activator P35/P39 only exists in the nervous system, therefore, it plays key role in the nervous system.Until now, it has not been reported that KCl induces expression of Trx,CDK5.Our study explored that KCl induced expression of Trx,CDK5 and related mechanisms by using PC12 pheochromocytoma cells. Our data showed that the expression of Trx and CDK5 were increased after exposure to KCl in PC12 cells. In addition, the inhibitor of N-methyl-d-aspartate receptors (NMDAR), MK-801 Calcium/calmodulin-dependent protein kinaseâ…¡(CaMKII), KN-62,extracellular signal-regulated kinase (ERK), PD98059 suppressed the expression of Trx and CDK5 induced by KCl. Furthermore, pretreated with KCl protected PC12 cells from damage by 1-Methyl-4-phenylpyridinium ion (MPP+), and the decreased expression of the Trx and CDK5 by MPP+were restored by KCl. Our data suggested that KCl depolarization protects neurons is related to the expression of Trx and CDK5. KCl promoted cell growth and protected cells from damage by MPP+ through MNDA receptors, CaMKII, ERK signaling pathway.Taken together, our study showed that KCl induced expression of Trx and CDK5 and related signaling pathways. The roles of KCl in cell growth and the protection of PC12 cells are asscoiated with expression of Trx and CDK5. These results provide a theoretical basis for KCl as a new drug to treat neurodegenerative diseases.