title: Phorbol ester increases mitochondrial cholesterol content in NCI H295R cells.
abstract: The first step in steroidogenesis is cholesterol mobilization from cytosolic lipid droplets to the initiating rate-limiting enzyme complex located on the inner mitochondrial membrane. Angiotensin II (AngII), the primary agonist of aldosterone secretion from adrenal glomerulosa cells, is known to induce cholesterol mobilization to mitochondria. However, the role of the protein kinase C (PKC) pathway in mediating cholesterol mobilization is unknown. To determine PKC's involvement, human adrenocortical carcinoma cells were incubated with or without PKC-activating phorbol 12-myristate 13-acetate (PMA) and mitochondrial cholesterol content assayed. Like AngII, PMA significantly elevated mitochondrial cholesterol content as well as aldosterone secretion. Thus, PKC may play a role in cholesterol mobilization to mitochondria and hence steroid production. Atrial natriuretic peptide (ANP) inhibited both AngII- and PMA-stimulated mitochondrial cholesterol content. These findings suggest that the ability of ANP to inhibit steroidogenesis induced by multiple agents may be related to its capacity to reduce cholesterol mobilization.
authors.affiliation: Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA 30912, USA. wbollag@mcg.edu
authors.forename: Wendy B
authors.initials: WB
authors.lastname: Bollag
authors.forename: Patricia
authors.initials: P
authors.lastname: Kent
authors.forename: Stephanie
authors.initials: S
authors.lastname: White
authors.forename: Mariya V
authors.initials: MV
authors.lastname: Wilson
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Isales
authors.forename: Roberto A
authors.initials: RA
authors.lastname: Calle
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000378:metabolism / Q000473:pathology*; D018268:Adrenocortical Carcinoma / Q000378:metabolism / Q000473:pathology*; D000804:Angiotensin II / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010703:Phorbol Esters / Q000494:pharmacology*; D013256:Steroids / Q000378:metabolism
chemical_list: D010703:Phorbol Esters; D013256:Steroids; D000804:Angiotensin II; C119222:phorbol-12-myristate; D009320:Atrial Natriuretic Factor; D002784:Cholesterol
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