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

Abstract
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).
AuthorsHai-Kang Zhao, Bao-Ying Chen, Rui Chang, Jian-Bang Wang, Feng Ni, Lei Yang, Xi-Chao Dong, Shu-Hu Sun, Ge Zhao, Wei Fang, Quan-Rui Ma, Xue-Lian Wang, Jun Yu
JournalPeptides (Peptides) Vol. 49 Pg. 117-22 (Nov 2013) ISSN: 1873-5169 [Electronic] United States
PMID24055805 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2013 Elsevier Inc. All rights reserved.
Chemical References
  • Neuroprotective Agents
  • ventricular natriuretic peptide, eel
  • Atrial Natriuretic Factor
  • 1-Methyl-4-phenylpyridinium
  • Dopamine
Topics
  • 1-Methyl-4-phenylpyridinium (toxicity)
  • Animals
  • Atrial Natriuretic Factor (pharmacology)
  • Dopamine (metabolism)
  • Mice
  • Mice, Inbred C57BL
  • Neurons (drug effects, metabolism)
  • Neuroprotective Agents (toxicity)

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