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Effects of Acute Exposure to an Environmental Electrophile on Human Platelet Bioenergetics
Citation:
Shen, W., H. Tong, D. Diaz-Sanchez, Andy Ghio, K. Lavrich, AND J. Samet. Effects of Acute Exposure to an Environmental Electrophile on Human Platelet Bioenergetics. Society of Toxicology (SOT) Annual Meeting, San Antonio, TX, March 10 - 15, 2018.
Impact/Purpose:
This is an abstract of a proposed presentation in poster format of findings from a mechanistic study in which human blood platelets were exposed to organic PM components and the ensuing effect on cellular bioenergetics was characterized.
Description:
Exposure to air pollution is a global public health problem associated with cardiovascular morbidity and mortality. Exposure to particulate matter (PM) has been reported to activate circulating platelets in vulnerable populations (patients with type 2 diabetes or coronary heart disease) within hours of exposure. 1,2-Naphthoquinone (1,2-NQ) is an oxidative environmental stressor found associated with diesel exhaust particles. Given the dependence of platelet function on cellular bioenergetics, we investigated the effect of exposure to 1,2-NQ oxygen consumption rates (OCR) in human platelets using extracellular flux technology. Human platelets (HP) were isolated from venous blood collected from healthy male subjects using IRB approved protocols. HP (30 million per well, n=3-4 per treatment group) were isolated from a blood sample collected on the day of the assay and subjected to a mitochondrial stress test using an extracellular flux analyzer (Seahorse platform) in order to assess indices of mitochondrial respiration inferred from changes in oxygen consumption rates (OCR) in response to specific inhibitors. Treatment of HP with a concentration of 1,2-NQ as low as 3 µM decreased the mitochondrial basal respiration, maximal respiration, and spare respiratory capacity in HP, while a dose of 10 µM of 1,2 NQ increased non-mitochondrial respiration,possibly associated with redox cycling, compared to vehicle-treated controls,. These findings provide insights into the mechanisms through which exposure to environmentalr contaminants can affect cellular bioenergetics and suggest potential effects of air pollution exposure on hemostasis and cardiovascular health. THIS ABSTRACT OF A PROPOSED PRESENTATION DOES NOT NECESSARILY REFLECT EPA POLICY.