New Enzymes Involved in the Mechanism of Action of Epidermal Growth Factor in a Clonal Strain of Leydig Tumor Cells
Autor: | Rocío Castilla, Mariana C. Gadaleta, Alejandra Duarte, Ernesto J. Podestá, Ana Fernanda Castillo, Fabiana Cornejo Maciel, Cristina Paz, Isabel Neuman |
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Rok vydání: | 2008 |
Předmět: |
Male
medicine.medical_specialty Blotting Western Biology Mitochondrion chemistry.chemical_compound Endocrinology Epidermal growth factor Cell Line Tumor Internal medicine Coenzyme A Ligases medicine Animals Cells Cultured Messenger RNA Arachidonic Acid Epidermal Growth Factor Leydig cell Reverse Transcriptase Polymerase Chain Reaction Steroidogenic acute regulatory protein Leydig Cells Phosphoproteins Clone Cells Mitochondria Rats medicine.anatomical_structure Mechanism of action chemistry ACOT2 Arachidonic acid Thiolester Hydrolases medicine.symptom Leydig Cell Tumor |
Zdroj: | Endocrinology. 149:3743-3752 |
ISSN: | 1945-7170 0013-7227 |
Popis: | The studies presented herein were designed to investigate the effect of mouse epidermal growth factor (mEGF) on arachidonic acid (AA) release in a clonal strain of cultured murine Leydig cells (designed MA-10). In MA-10 cells, mEGF promotes AA release and metabolism to lipoxygenated products to induce the steroidogenic acute regulatory (StAR) protein. However, the mechanism by which mEGF releases AA in these cells is not totally elucidated. We show that mEGF produces an increment in the mitochondrial AA content in a short-term incubation (30 min). This AA is released by the action of a mitochondrial acyl-CoA thioesterase (Acot2), as demonstrated in experiments in which Acot2 was down or overexpressed. This AA in turn regulates the StAR protein expression, indirect evidence of its metabolism to lipoxygenated products. We also show that mEGF induces the expression (mRNA and protein) of Acot2 and an acyl-CoA synthetase that provides the substrate, arachidonyl-CoA, to Acot2. This effect is also observed in another steroidogenic cell line, the adrenocortical Y1 cells. Taken together, our results show that: 1) mEGF can induce the generation of AA in a specific compartment of the cells, i.e. the mitochondria; 2) mEGF can up-regulate acyl-CoA synthetase and Acot2 mRNA and protein levels; and 3) mEGF-stimulated intramitochondrial AA release leads to StAR protein induction. |
Databáze: | OpenAIRE |
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