Projects per year
Abstract
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.
Original language | English |
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Article number | BSR20194404 |
Journal | Bioscience Reports |
Volume | 40 |
Issue number | 4 |
DOIs | |
State | Published - 1 Apr 2020 |
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Dive into the research topics of 'MEHP interferes with mitochondrial functions and homeostasis in skeletal muscle cells'. Together they form a unique fingerprint.Projects
- 3 Finished
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Exploring the Trpv1 and Pgc-1α Crosstalk Mechanisms Mediating the Effects of Plasticizers on Muscle Cell Differentiation and Metabolism(III)
Chen, S.-L. (PI)
1/08/18 → 31/07/19
Project: Research
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Exploring the Trpv1 and Pgc-1α Crosstalk Mechanisms Mediating the Effects of Plasticizers on Muscle Cell Differentiation and Metabolism( II )
Chen, S.-L. (PI)
1/08/17 → 31/07/18
Project: Research
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Exploring the Trpv1 and Pgc-1α Crosstalk Mechanisms Mediating the Effects of Plasticizers on Muscle Cell Differentiation and Metabolism( I )
Chen, S.-L. (PI)
1/08/16 → 31/07/17
Project: Research