title: Role of intramitochondrial arachidonic acid and acyl-CoA synthetase 4 in angiotensin II-regulated aldosterone synthesis in NCI-H295R adrenocortical cell line.
abstract: Although the role of arachidonic acid (AA) in angiotensin II (ANG II)- and potassium-stimulated steroid production in zona glomerulosa cells is well documented, the mechanism responsible for AA release is not fully described. In this study we evaluated the mechanism involved in the release of intramitochondrial AA and its role in the regulation of aldosterone synthesis by ANG II in glomerulosa cells. We show that ANG II and potassium induce the expression of acyl-coenzyme A (CoA) thioesterase 2 and acyl-CoA synthetase 4, two enzymes involved in intramitochondrial AA generation/export system well characterized in other steroidogenic systems. We demonstrate that mitochondrial ATP is required for AA generation/export system, steroid production, and steroidogenic acute regulatory protein induction. We also demonstrate the role of protein tyrosine phosphatases regulating acyl-CoA synthetase 4 and steroidogenic acute regulatory protein induction, and hence ANG II-stimulated aldosterone synthesis.
authors.affiliation: Department of Biochemistry, School of Medicine, University of Buenos Aires, Institute of Biomedical Investigations, UBA-Consejo Nacional de Investigaciones Científicas y Técnicas, Paraguay 2155, 5 Floor, C1121ABG Buenos Aires, Argentina.
authors.forename: Pablo G
authors.initials: PG
authors.lastname: Mele
authors.forename: Alejandra
authors.initials: A
authors.lastname: Duarte
authors.forename: Cristina
authors.initials: C
authors.lastname: Paz
authors.forename: Alessandro
authors.initials: A
authors.lastname: Capponi
authors.forename: Ernesto J
authors.initials: EJ
authors.lastname: Podestá
mesh_terms: D000450:Aldosterone / Q000378:metabolism*; D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002417:Cattle; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007985:Leydig Cells / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D054467:Phospholipases A2 / Q000378:metabolism; D015384:Zona Glomerulosa / Q000378:metabolism
chemical_list: D000450:Aldosterone; D000804:Angiotensin II; D016718:Arachidonic Acid; D051792:Basic Helix-Loop-Helix Proteins; D054467:Phospholipases A2; C499123:ASCL4 protein, human