Rotenone-induced cellular dysfunction in human blood platelets: Unraveling calcium dysregulation, mitochondrial impairment, oxidative stress, and apoptosis
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LC-MS Analysis of Human Platelets as a Platform for Studying Mitochondrial Metabolism
Published on: April 4, 2016
Samir Kumar Beura1, Nisha Yadav1, Abhishek Kumar Maurya1
1Department of Biochemistry, School of Basic Sciences, Central University of Punjab, Ghudda, Bathinda, Punjab 151401, India.
Abstract:
Rotenone, a naturally occurring pesticide and a well-established mitochondrial complex I inhibitor, disrupts electron transport chain activity, resulting in impaired energy metabolism, oxidative stress, and apoptosis. Our recent findings revealed that rotenone suppresses agonist-induced platelet functional activity; however, the molecular mechanisms underlying this effect remain largely unclear. In this study, we demonstrate that rotenone exposure induces pronounced cytotoxic effects in human platelets, evident from decreased cell viability and phosphatidylserine externalization, a hallmark of apoptosis-like processes. At the mitochondrial level, rotenone markedly compromises organelle integrity by inducing mitochondrial membrane potential depolarization, excessive reactive oxygen species generation, and calcium dysregulation. These mitochondrial perturbations act as key upstream signals that trigger caspase activation and drive apoptosis-like cascades in platelets. Collectively, our findings identify mitochondrial dysfunction, oxidative stress, and calcium imbalance as central mediators of rotenone-induced, caspase-dependent platelet apoptosis. This study demonstrates that rotenone induces cytotoxicity and organelle dysfunction in human blood platelets, thereby providing mechanistic insight into altered platelet functions.
Insights
Rotenone pesticide induces cell death in human platelets by damaging mitochondria, leading to impaired function. This pesticide causes oxidative stress and calcium imbalance, triggering programmed cell death pathways in platelets.
Area of Science:
- Biochemistry
- Toxicology
- Cell Biology
Background:
- Rotenone is a pesticide known to inhibit mitochondrial complex I.
- Rotenone affects platelet function, but the underlying mechanisms are unclear.
- Platelets play a crucial role in hemostasis and thrombosis.
Purpose of the Study:
- To elucidate the molecular mechanisms of rotenone-induced platelet dysfunction.
- To investigate the effects of rotenone on human platelet viability and apoptosis.
- To examine rotenone's impact on mitochondrial integrity and function in platelets.
Main Methods:
- Human platelets were exposed to rotenone.
- Cell viability was assessed using assays for cytotoxicity and phosphatidylserine externalization.
- Mitochondrial function was evaluated by measuring membrane potential, reactive oxygen species (ROS) generation, and calcium levels.
- Caspase activation was analyzed to determine apoptosis pathways.
Main Results:
- Rotenone exposure led to decreased human platelet viability and phosphatidylserine externalization, indicating apoptosis.
- Rotenone disrupted mitochondrial integrity, causing membrane potential depolarization, increased ROS production, and calcium dysregulation.
- Mitochondrial dysfunction preceded and triggered caspase activation, driving platelet apoptosis.
- These events provide mechanistic insight into rotenone's effects on platelet function.
Conclusions:
- Rotenone induces significant cytotoxicity and mitochondrial dysfunction in human platelets.
- Mitochondrial damage, oxidative stress, and calcium imbalance are key mediators of rotenone-induced platelet apoptosis.
- This study clarifies the mechanisms behind rotenone's impact on platelet function and viability.
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