Investigating the role of rotenone on human blood platelets: Molecular insights into abnormal platelet functions in Parkinson's disease

• Published in: Journal of biochemical and molecular toxicology Vol. 38; no. 6; pp. e23747 - n/a
• Main Authors: Beura, Samir Kumar, Sahoo, Gaurahari, Yadav, Sonika, Yadav, Pooja, Panigrahi, Abhishek Ramachandra, Singh, Sunil Kumar
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.06.2024
• Subjects: Blood; Blood circulation; blood platelet; Blood platelets; Blood Platelets - drug effects; Blood Platelets - metabolism; Calcium ions; Calcium mobilization; Dopamine receptors; Health services; Humans; Inositols; Kinases; Mesencephalon; Molecular modelling; Movement disorders; NAD(P)H oxidase; Neurodegenerative diseases; Neurons; neurotoxin; Neurotoxins; Parkinson Disease - blood; Parkinson Disease - metabolism; Parkinson's disease; Patients; Platelets; Protein kinase C; Reactive oxygen species; Reactive Oxygen Species - metabolism; Rot; Rotenone; Rotenone - pharmacology; Thrombin; Toxins; neurotoxin; rotenone; blood platelet; Parkinson's disease; reactive oxygen species
• ISSN: 1095-6670; 1099-0461
• DOI: 10.1002/jbt.23747

Parkinson's disease (PD) is a predominant neuromotor disorder characterized by the selective death of dopaminergic neurons in the midbrain. The majority of PD cases are sporadic or idiopathic, with environmental toxins and pollutants potentially contributing to its development or exacerbation. However, clinical PD patients are often associated with a reduced stroke frequency, where circulating blood platelets are indispensable. Although platelet structural impairment is evident in PD, the platelet functional alterations and their underlying molecular mechanisms are still obscure. Therefore, we investigated rotenone (ROT), an environmental neurotoxin that selectively destroys dopaminergic neurons mimicking PD, on human blood platelets to explore its impact on platelet functions, thus replicating PD conditions in vitro. Our study deciphered that ROT decreased thrombin‐induced platelet functions, including adhesion, activation, secretion, and aggregation in human blood platelets. As ROT is primarily responsible for generating intracellular reactive oxygen species (ROS), and ROS is a key player regulating the platelet functional parameters, we went on to check the effect of ROT on platelet ROS production. In our investigation, it became evident that ROT treatment resulted in the stimulation of ROS production in human blood platelets. Additionally, we discovered that ROT induced ROS production by augmenting Ca2+ mobilization from inositol 1,4,5‐trisphosphate receptor. Apart from this, the treatment of ROT triggers protein kinase C associated NADPH oxidase‐mediated ROS production in platelets. In summary, this research, for the first time, highlights ROT‐induced abnormal platelet functions and may provide a mechanistic insight into the altered platelet activities observed in PD patients. Cellular and molecular mechanism of rotenone (ROT)—an environmental neurotoxin mediated abnormal platelet functions in Parkinson's disease model.