Unveiling the mechanism of platelet dysfunction in Parkinson's disease: The effect of 6-hydroxydopamine on human blood platelets

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dc.contributor.authorBeura, Samir Kumar
dc.contributor.authorYadav, Pooja
dc.contributor.authorPanigrahi, Abhishek Ramachandra
dc.contributor.authorSingh, Sunil Kumar
dc.date.accessioned2024-01-21T10:44:47Z
dc.date.accessioned2024-08-13T13:21:49Z
dc.date.available2024-01-21T10:44:47Z
dc.date.available2024-08-13T13:21:49Z
dc.date.issued2023-05-22T00:00:00
dc.description.abstractIntroduction: Parkinson's disease (PD) is a progressive neuronal illness often linked to increased cardiovascular complications, such as myocardial infarction, cardiomyopathy, congestive heart failure, and coronary heart disease. Platelets, which are the essential components of circulating blood, are considered potential players in regulating these complications, as platelet dysfunction is evident in PD. These tiny blood cell fragments are supposed to play a crucial role in these complications, but the underlying molecular processes are still obscure. Methods: To gain a better understanding of platelet dysfunction in PD, we investigated the impact of 6-hydroxydopamine (6-OHDA), an analog of dopamine that simulates PD by destroying dopaminergic neurons, on human blood platelets. The levels of intraplatelet reactive oxygen species (ROS) were assessed using H2DCF-DA (20 ?M), while mitochondrial ROS was evaluated using MitoSOX� Red (5 ?M), and intracellular Ca2+ was measured with Fluo-4-AM (5 ?M). The data were acquired through the use of both a multimode plate reader and a laser-scanning confocal microscope. Results: Our findings showed that 6-OHDA treatment increased the production of ROS in human blood platelets. The increase in ROS was confirmed by the ROS scavenger, NAC, and was also reduced by inhibiting the NOX enzyme with apocynin. Additionally, 6-OHDA potentiated mitochondrial ROS production in platelets. Furthermore, 6-OHDA triggered the intraplatelet Ca2+ elevation. This effect was mitigated by the Ca2+ chelator BAPTA, which decreased the ROS production triggered by 6-OHDA in human blood platelets, while the IP3 receptor blocker, 2-APB, reduced the formation of ROS induced by 6-OHDA. Conclusion: Our findings suggest that the 6-OHDA-induced ROS production is regulated by the IP3 receptor-Ca2+-NOX signaling axis in human blood platelets, where the platelet mitochondria also play a significant role. This observation provides a crucial mechanistic understanding of the altered platelet activities that are commonly observed in PD patients. � 2023 Elsevier Ltden_US
dc.identifier.doi10.1016/j.parkreldis.2023.105453
dc.identifier.issn13538020
dc.identifier.urihttp://10.2.3.109/handle/32116/3859
dc.identifier.urlhttps://linkinghub.elsevier.com/retrieve/pii/S1353802023001761
dc.language.isoen_USen_US
dc.publisherElsevier Ltden_US
dc.subject6-Hydroxydopamineen_US
dc.subjectBlood plateleten_US
dc.subjectIntracellular Ca<sup>2+</sup>en_US
dc.subjectIP<sub>3</sub> receptoren_US
dc.subjectMitochondrial ROSen_US
dc.subjectNADPH oxidaseen_US
dc.subjectParkinson's diseaseen_US
dc.titleUnveiling the mechanism of platelet dysfunction in Parkinson's disease: The effect of 6-hydroxydopamine on human blood plateletsen_US
dc.title.journalParkinsonism and Related Disordersen_US
dc.typeArticleen_US
dc.type.accesstypeClosed Accessen_US

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