Decreased CytochromecOxidase IV Expression Reduces Steroidogenesis
| Autor: | Himangshu S. Bose, John P. Wiebe, Kevin J. Pawlak, C. Gary Gairola, Kevin A. McKenzie, Manoj Prasad, Randy M. Whittal |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Down-Regulation
Dehydroepiandrosterone Oxidative phosphorylation Gene Expression Regulation Enzymologic Electron Transport Complex IV Mice Random Allocation Chlorocebus aethiops medicine Animals Cytochrome c oxidase Inner mitochondrial membrane Progesterone Pharmacology biology Steroidogenic acute regulatory protein Cholesterol side-chain cleavage enzyme Smoking Cytochrome P450 Mice Inbred C57BL Endocrine and Diabetes Biochemistry Gene Knockdown Techniques Pregnenolone COS Cells biology.protein Molecular Medicine Female Steroids medicine.drug |
| Zdroj: | Journal of Pharmacology and Experimental Therapeutics. 338:598-604 |
| ISSN: | 1521-0103 0022-3565 |
| DOI: | 10.1124/jpet.111.182634 |
| Popis: | Steroidogenic acute regulatory protein facilitates the translocation of cholesterol to the inner mitochondrial membrane, thereby initiating steroidogenesis. At the inner mitochondrial membrane, cytochrome P450 side-chain cleavage enzyme converts cholesterol to pregnenolone, an oxidative process requiring electrons from NADPH. Pregnenolone then serves as the substrate for the formation of progesterone or dehydroepiandrosterone by downstream enzymes. Studies have shown that cigarette smoke (CS) influences steroid hormone levels. To better understand the underlying mechanisms, we used a mouse model to study the effects of chronic CS exposure on steroidogenesis. Through radioimmunoassay and metabolic conversion assays, we found that CS reduced progesterone and dehydroepiandrosterone without affecting cytochrome P450 side-chain cleavage enzyme or 3β-hydroxysteroid dehydrogenase 2 expression. However, CS did reduce expression of cytochrome c oxidase IV (COX IV), a component of the mitochondrial complex that serves as the last enzyme in the electron transport chain. Small interfering RNA-mediated COX IV knockdown indeed decreased progesterone synthesis in steroidogenic cells. In summary, COX IV likely plays a role in steroidogenesis, and passive smoking may negatively affect steroidogenesis by disrupting the electron transport chain. |
| Databáze: | OpenAIRE |
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