MEHP interferes with mitochondrial functions and homeostasis in skeletal muscle cells.

Yi-Huan Chen, Yi-Ju Wu, Wei-Cheng Chen, Tzong-Shyuan Lee, Tsui-Chun Tsou, Hsuan-Chia Chang, Sheng-Wen Lo, Shen-Liang Chen

Bioscience reports 2020 Apr 30

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Di (2-ethylhexyl) phthalate (DEHP) is a plasticizer frequently leached out from polyvinyl chloride (PVC) products and is quickly metabolized to its monoester equivalent mono(2-ethylhexyl) phthalate (MEHP) once enters organisms. Exposure to DEHP/MEHP through food chain intake has been shown to modified metabolism but its effect on the development of metabolic myopathy of skeletal muscle (SKM) has not been revealed so far. Here, we found that MEHP repressed myogenic terminal differentiation of proliferating myoblasts (PMB) and confluent myoblasts (CMB) but had weak effect on this process once it had been initiated. The transition of mitochondria (MITO) morphology from high efficient filamentary network to low efficient vesicles was triggered by MEHP, implying its negative effects on MITO functions. The impaired MITO functions was further demonstrated by reduced MITO DNA (mtDNA) level and SDH enzyme activity as well as highly increased reactive oxygen species (ROS) in cells after MEHP treatment. The expression of metabolic genes, including PDK4, CPT1b, UCP2, and HO1, was highly increased by MEHP and the promoters of PDK4 and CPT1b were also activated by MEHP. Additionally, the stability of some subunits in the oxidative phosphorylation system (OXPHOS) complexes was found to be reduced by MEHP, implying defective oxidative metabolism in MITO and which was confirmed by repressed palmitic acid oxidation in MEHP-treated cells. Besides, MEHP also blocked insulin-induced glucose uptake. Taken together, our results suggest that MEHP is inhibitory to myogenesis and is harmful to MITO functions in SKM, so its exposure should be avoided or limited. © 2020 The Author(s).

Citation

Yi-Huan Chen, Yi-Ju Wu, Wei-Cheng Chen, Tzong-Shyuan Lee, Tsui-Chun Tsou, Hsuan-Chia Chang, Sheng-Wen Lo, Shen-Liang Chen. MEHP interferes with mitochondrial functions and homeostasis in skeletal muscle cells. Bioscience reports. 2020 Apr 30;40(4)