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).
Department of Neurosurgery, Second Affiliated Hospital, Xi'an Medical University, Xi'an, China.
Hai-Kang
HK
Zhao
Bao-Ying
BY
Chen
Rui
R
Chang
Jian-Bang
JB
Wang
Feng
F
Ni
Lei
L
Yang
Xi-Chao
XC
Dong
Shu-Hu
SH
Sun
Ge
G
Zhao
Wei
W
Fang
Quan-Rui
QR
Ma
Xue-Lian
XL
Wang
Jun
J
Yu
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000633:toxicity*
D018696:Neuroprotective Agents; C068986:ventricular natriuretic peptide, eel; D009320:Atrial Natriuretic Factor; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine
Dopaminergic neurons; N-methyl-4-phenylpyridinium; Natriuretic peptides; Parkinson's disease