Hotspot in the research of Parkinson disease: the protective effects of 3-nitropropionic acid preconditioning on dopaminergic neurons

Xuejun DENG; Shenggang SUN; Xuebing CAO; Hongge LI; Zhihou LIANG

ABSTRACT

BACKGROUND:

3-nitropropionic acid(3-NP) can inhibit the process of oxidative phosphorylation and injure the energy metabolism of the cell and thereby induce cell injury. However, small dose of 3-NP can excite intrinsic cellular protective factor to protect neurons and increase the tolerance of neurons to ischemic hypoxia through mild inhibiting the process of oxidative phosphorylation. It is unclear whether it also has the similar effect on dopaminergic neurons.

OBJECTIVE:

To investigate whether 3-NP preconditioning could enhance the tolerance of dopaminergic neurons to MPP+(1-methyl-4-phenylpyridine)toxicity.

DESIGN:

A randomized controlled exploring research based on neuroblastoma SH-SYSY cell that could secrete dopamine.

SETTING:

Department of neurology of a university hospital.MATERIALS The study was conducted in the Laboratory of Pathophysiology of Tongji Medical College between March 2003 and November 2003. SH-SYSY cell was obtained from the Cell Center of Peking Union Medical University.

INTERVENTIONS:

Cells were randomly divided into 6 groups. MPP+ was added into the cultured dopaminergic neuron SH-SY5Y cells for the establishment of the cell model for Parkinson disease. Before the admission of MPP+ (0.25 mmol/L), 3-NP(0. 2 mmol/L) was added once or repetitive times to form preconditioning. Microculture tetrozolium(MTT) was used to detect cell survival rate, and[3H] DA uptake rate was used to test the anterior synaptic function of dopaminergic neurons.MAIN OUTCOME

MEASURES:

Major consequence Cell survival rate;Minor consequence [3H] DA uptake rate.

RESULTS:

Cell survival rate of MPP+ group was 54.3%, which was significantly lower than that of blank control group( P ＜ 0.01) . After 3-NP preconditioning, cell survival rate significantly elevated, which was 71.8%(single) or 85.2% (repetitive) . There was significant difference between single preconditioning and repetitive preconditioning( P ＜ 0.05 ). The results of[3H] DA uptake rate were similar to that of cell survival rate. [3H] DA uptake rate was 65.8% (single) or 80. 3% (repetitive), which was significantly higher than 50. 1% of MPP+ group. And moreover, repetitive preconditioning had more favorable effect than single preconditioning. Simple admission of 3-NP had no impact on cells.

CONCLUSION:

3-NP preconditioning can significantly enhance the tolerance of dopaminergic neuron to MPP+ toxicity, which has significant protective effects on dopaminergic neuron. Repetitive preconditioning have more significant protective effects.