Phorbol ester increases mitochondrial cholesterol content in NCI H295R cells.
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.
Bollag
Wendy B
WB
Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA 30912, USA. wbollag@mcg.edu
Kent
Patricia
P
White
Stephanie
S
Wilson
Mariya V
MV
Isales
Carlos M
CM
Calle
Roberto A
RA
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
D010703:Phorbol Esters; D013256:Steroids; D000804:Angiotensin II; C119222:phorbol-12-myristate; D009320:Atrial Natriuretic Factor; D002784:Cholesterol
Biochem J. 1986 Jul 1;237(1):253-8
3800878
Mol Endocrinol. 2007 Mar;21(3):589-601
16973755
Endocrinology. 2003 Nov;144(11):4905-15
12960096
Endocrinology. 2005 Jun;146(6):2544-50
15774560
Mol Cell Endocrinol. 1996 Apr 19;118(1-2):137-44
8735599
J Cell Sci. 2002 Dec 1;115(Pt 23):4399-411
12414987
Mol Cell Endocrinol. 1999 Aug 20;154(1-2):1-9
10509794
Mol Cell Endocrinol. 2003 Aug 29;206(1-2):113-22
12943994
J Biol Chem. 1996 Oct 18;271(42):25971-5
8824233
Endocrinology. 2006 Dec;147(12):6046-55
16973724
Biochem Biophys Res Commun. 1983 Oct 31;116(2):555-62
6418161
J Lipid Res. 1978 Nov;19(8):1068-70
731127
Endocr Rev. 1996 Jun;17(3):269-88
8771360
Endocrinology. 1993 Oct;133(4):1555-61
8404594
Endocrinology. 1990 Sep;127(3):1436-43
1696885
Biochem Biophys Res Commun. 1992 Jan 15;182(1):254-61
1731785
Mol Cell Endocrinol. 2001 May 25;177(1-2):71-9
11377822
Mol Cell Endocrinol. 2002 Jun 28;192(1-2):7-16
12088862
Mol Endocrinol. 1998 Jul;12(7):962-72
9658401
Endocr Rev. 1995 Oct;16(5):649-81
8529575
Mol Endocrinol. 2001 Aug;15(8):1245-54
11463850
Endocrinology. 1995 Dec;136(12):5677-84
7588323
Am J Physiol. 1989 Jan;256(1 Pt 1):C89-95
2521426
Trends Pharmacol Sci. 2006 Jun;27(6):317-23
16678913
Cell Signal. 2007 Aug;19(8):1633-42
17537614
Cell Mol Life Sci. 2005 Oct;62(19-20):2305-16
16143829
Endocrinology. 1992 Apr;130(4):2230-6
1547736
Endocr Rev. 1989 Nov;10(4):496-518
2558878