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

Kyung Min Lim, Hyun Hee Kim, Ok Nam Bae, Ji Yoon Noh, Keun Young Kim, Sae Hwan Kim, Seung Min Chung, Sue Shin, Hyeon Yeong Kim, Jin Ho Chung

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

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.

Original languageEnglish
Pages (from-to)163-170
Number of pages8
JournalPlatelets
Volume20
Issue number3
DOIs
StatePublished - May 2009

Bibliographical note

Funding Information:
This work was supported by the Grants from Chemical Safety and Health Agency, and KOSEF grant funded by the MOST (R01-2007-000-11252-0).

Keywords

  • ATP
  • MPP+
  • MPTP
  • Parkinson's disease
  • Platelet aggregation

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