Morphine reverses the effects of 1-methyl-4-phenylpyridinium in PC12 cells through activating PI3K/Akt

Abstract

Aim of the study: Parkinson’s disease (PD) is a neurodegenerative disorder. It is caused by the degeneration of dopaminergic neurons and the dopamine (DA) deletion in the substantia nigra pars compacta (SNpc). Morphine elevates the level of dopamine in the mesolimbic dopamine system and plays a role in alleviating PD symptoms. However, the molecular mechanism is still unclear. The aim of the study is to investigate the mechanism on morphine alleviating PD symptoms.

Materials and methods: The viability of PC12 cells was measured by using MTT assay. The expressions of tyrosine hydroxylase (TH), thioredoxin-1 (Trx-1), CyclinD1 and Cyclin-dependent kinase5 (Cdk5) were detected by Western Blot.

Results: In present study, we found that morphine increased the cell viability in PC12 cells. 1-methyl-4-phenylpyridi-nium (MPP+) reduced the cell viability and TH expression, which were reversed by morphine. MPP+ decreased the expressions of Trx-1, CyclinD1, Cdk5, which were restored by morphine. Moreover, the role of morphine in restoring the expressions of Trx-1, CyclinD1 and Cdk5 decreased by MPP+ was abolished by LY294002, phosphatidylinositol-3-kinase (PI3K)/Akt inhibitor.

Conclusions: These results suggest that morphine reverses effects induced by MPP þ through activating PI3K/Akt pathway.

Keywords:

• Thioredoxin-1
• morphine
• MPP⁺
• PI3K/Akt

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China under Grant [number 81660222]; the National Natural Science Foundation of China under Grant [number U1202227]; and National Natural Science Foundation of China under Grant [number 81460167] and Program for Innovative Research Team (in Science and Technology) in University of Yunnan Province.