Vasonatrin peptide, a novel protector of dopaminergic neurons against the injuries induced by n-methyl-4-phenylpyridiniums

Vasonatrin peptide (VNP), a novel manmade natriuretic peptide, is known as a cardiovascular active substance. However, its neuroeffects are largely unknown. Here, cultured dopaminergic neurons from ventral mesencephalon of mouse were exposed to N-methyl-4-phenylpyridinium (MPP(+)), and the effects of VNP on the neurotoxicity of MPP(+) were investigated. As a result, MPP(+) caused injuries in the dopaminergic neurons. VNP significantly reduced the cytotoxicity of MPP(+) by increasing axon number and length of dopaminergic neurons, and by enhancing the cell viability. Also, the MPP(+)-induced depolymerization of β-Tubulin III was attenuated by the treatment of VNP. In addition, VNP significantly increased the intracellular levels of cGMP. These effects of VNP were mimicked by 8-br-cGMP (a cell-permeable analog of cGMP), whereas inhibited by HS-142-1 (the antagonist of the particulate guanylyl cyclase-coupled natriuretic peptide receptors), or KT-5823 (a cGMP-dependent protein kinase inhibitor). Taken together, VNP attenuates the neurotoxicity of MPP(+) via guanylyl cyclase-coupled NPR/cGMP/PKG pathway, indicating that VNP might be a new effective reagent in the treatment of neuron degeneration of dopaminergic neurons in Parkinson's disease (PD).