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Inhibition of platelet aggregation by 1-methyl-4-phenyl pyridinium ion (MPP plus ) through ATP depletion: Evidence for the reduced platelet activities in Parkinson's disease

Title
Inhibition of platelet aggregation by 1-methyl-4-phenyl pyridinium ion (MPP plus ) through ATP depletion: Evidence for the reduced platelet activities in Parkinson's disease
Author
배옥남
Keywords
MPTP; MPP; ATP; platelet aggregation; Parkinson's disease
Issue Date
2009-04
Publisher
TAYLOR & FRANCIS LTD
Citation
PLATELETS, v. 20, v. 3, Page. 163-170
Abstract
Neuronal accumulation of 1-methyl-4-phenylpyridinium ion (MPP+), the metabolite of neural toxin, 1-methyl-4-phenyl-1,2,3,6-tetrahyropyridine (MPTP), induces a rapid depletion of cellular ATP level and loss of neuronal cell viability which simulates human Parkinson's disease (PD). Since ATP plays an important role in the physiology and function of platelets, which share many biochemical and physiological features with neuronal cells, we examined the effect of MPP+ on platelet aggregation and viability using freshly isolated rat platelets. While the treatment of MPP+ to platelets did not induce cytotoxicity, it significantly attenuated agonist-induced platelet aggregation in a concentration dependent manner. The inhibition of aggregation by MPP+ was mediated by the depletion of the cytoplasmic ATP pool and resultant decreased ATP secretion. Different from the previous reports in neuronal cells, MPP+ did not affect intracellular levels of glutathione and cytoplasmic Ca2+ in platelets. The combined treatment with MPP+ and 2-deoxyglucose, a glycolysis inhibitor, showed the additive effect in the decrease of ATP secretion and intracellular content. Consistent with these findings, inhibitory effects of MPP+ on platelet aggregation was significantly enhanced by the treatment with 2-deoxyglucose. In conclusion, these results suggested that MPP+ can induce ATP depletion in platelets and attenuate platelet aggregation providing a new theory on the reduced platelet activities in PD patients.
URI
https://www.tandfonline.com/doi/abs/10.1080/09537100902721746http://repository.hanyang.ac.kr/handle/20.500.11754/74989
ISSN
0953-7104
DOI
10.1080/09537100902721746
Appears in Collections:
COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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