Vasonatrin peptide,a novel protector of dopaminergic neurons against the injuries induced by n-methyl-4-phenylpyridiniums |
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Institution: | 1. Biomedical Engineering Research Division, School of Engineering, University of Glasgow, Glasgow, United Kingdom;2. Department of Medical Instrumentation Techniques Engineering, Technical Engineering College of Mosul, Northern Technical University, Mosul, Iraq;3. Department of Biomedical Engineering, NED University of Engineering & Technology, Karachi, Pakistan;4. Queen Elizabeth National Spinal Injuries Unit, Queen Elisabeth University Hospital, Glasgow, United Kingdom;1. Department of Computational Hydrosystems, Helmholtz Centre for Environmental Research - UFZ, Leipzig, Germany;2. Centre for Water in the Minerals Industry, Sustainable Minerals Institute, The University of Queensland, Brisbane, QLD, Australia;3. Institute for Geosciences, Friedrich Schiller University, Jena, Germany |
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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). |
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Keywords: | Natriuretic peptides Dopaminergic neurons N-methyl-4-phenylpyridinium Parkinson's disease |
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