Redox regulation of hormone sensitive lipase: Potential role in the mechanism of MEHP-induced stimulation of basal steroid synthesis in MA-10 Leydig cells
| Autor: | Kassim Traore, Christine Zhou, Vassilios Papadopoulos, Daniel B. Martinez-Arguelles, Barry R. Zirkin, Yunbo Li, Ninad Zaman |
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| Rok vydání: | 2018 |
| Předmět: |
Male
endocrine system medicine.medical_specialty Hormone-sensitive lipase Stimulation 010501 environmental sciences Steroid biosynthesis Endocrine Disruptors Toxicology 01 natural sciences 03 medical and health sciences chemistry.chemical_compound Mice Plasticizers Internal medicine Cell Line Tumor Diethylhexyl Phthalate medicine Animals Progesterone 030304 developmental biology 0105 earth and related environmental sciences chemistry.chemical_classification 0303 health sciences Reactive oxygen species Chemistry Leydig Cells Sterol Esterase Phosphoproteins Acetylcysteine Endocrinology Cholesterol Endocrine disruptor Cholesteryl ester Phosphorylation Signal transduction Reactive Oxygen Species Oxidation-Reduction |
| Zdroj: | Reproductive toxicology (Elmsford, N.Y.). 85 |
| ISSN: | 1873-1708 |
| Popis: | Mono-(2-ethylhexyl) phthalate (MEHP), the active metabolite of di-(2-ethylhexyl) phthalate (DEHP), is a plasticizer with endocrine disruptor activity that has been shown to stimulate basal steroid biosynthesis in Leydig cells. The mechanism by which it does so is unknown. Using MA-10 mouse tumor Leydig cells, we assessed the effects of MEHP on reactive oxygen species (ROS) levels, and on the signal transduction pathways that mobilize cholesterol. Exposure to 0–300 μM MEHP stimulated basal progesterone production in a dose-dependent manner. Progesterone stimulation was correlated with increases in the phosphorylation of hormone-sensitive lipase (HSL; aka cholesteryl ester hydrolase), which is involved in the production of free cholesterol, and of steroidogenic acute regulatory (STAR) protein expression. Co-treating MA-10 cells with MEHP and the ROS scavenger N-acetyl cysteine (NAC) blocked the activation of HSL, blunted MEHP-induced STAR, and reduced basal progesterone formation. These observations suggest that ROS generation by MEHP leads to activation of HSL and increase in STAR which, together, result in increased free-cholesterol bioavailability and progesterone formation. |
| Databáze: | OpenAIRE |
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