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C70-26 Transcriptional Regulators of Mitochondrial Biogenesis Are Attenuated in Macrophages by Polystyrene Exposure
Summary
Scientists exposed immune cells (macrophages) to tiny polystyrene microplastic particles—the kind found in styrofoam food containers and inhaled from the air—and found that the plastics reduced key proteins these cells need to keep their energy-producing mitochondria healthy. Since macrophages rely on properly functioning mitochondria to fight off infections and clean up debris in the body, this suggests that breathing in microplastics could weaken our immune system's ability to protect us. This early lab study used mouse cells, so more research is needed to confirm these effects happen the same way in humans.
Abstract Rationale Polystyrene (PS) comprises approximately 20% of plastic products, mainly single-use food containers. Plastics are degraded by physical stressors or environmental factors such as temperature, sunlight, and water. Microplastics (MPs) are characterized as particles with a size of < 5 mm. Air flow resuspends MPs, leading to inhalation and the deposition of 26 to 130 MPs in the human lungs per day. Polypropylene exposure has been shown to increase damage to the mitochondrial membranes in macrophages, with reduced macrophage function. However, the mechanisms of mitochondrial dysfunction are not well defined. The purpose of this study is to investigate the effect of PS on regulators of mitochondrial biogenesis. We determined the effects of exposure to PS on key regulators of mitochondrial transcription, transcription factor A (TFAM), and peroxisome proliferator-activated receptor (PPAR) γ coactivator-1α (PGC-1α). Methods RAW 264.7 mouse macrophages were exposed to Spherical PS with a 100 nm diameter at a concentration of 10 ug or 100 ug/well. Spherical and irregularly shaped PS with a 200 nm diameter were added at a 100 ug/well concentration. MPs were incubated for 6, 24, and 48 hours, then protein was extracted. Protein expression of TFAM and PGC-1α was determined by Western blot analysis. Results 100 ug of 100 nm PS significantly reduced (P < 0.05) TFAM at 6 hours. PGC-1α was significantly reduced (P < 0.05) by 10 ug and 100 ug of 100 nm PS at 6 hours, with a tendency towards reduction (P = 0.054) by exposure to 100 ug at 24 hours of culture. Contact with spherical 200 nm PS significantly reduced (P < 0.001) TFAM at 6 and 24 hours. Incubation with irregularly shaped 200 nm PS significantly reduced (P < 0.05) TFAM at 6 hours and tended to reduce (P = 0.051) at 24 hours. Likewise, PGC-1α was significantly reduced (P < 0.05) by spherical 200 nm PS at 6 and 24 hours, as well as irregularly shaped 200 nm PS at 6 hours of exposure. Conclusion Our data show that exposure to polystyrene particles attenuates the expression of key transcriptional regulators of mitochondrial biogenesis, TFAM, and PGC-1α. This attenuation may contribute to mitochondrial dysfunction and ATP production in macrophages, resulting in altered innate immune function of macrophages. Further studies to investigate the impact of PS on mitochondrial bioenergetics and macrophage phagocytosis will determine how PS can have deleterious effects, potentially limiting the immune cell’s activity. This abstract is funded by: I01 BX001786