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Titolo:
OXYSTEROL REGULATION OF STEROIDOGENIC ACUTE REGULATORY PROTEIN GENE-EXPRESSION - STRUCTURAL SPECIFICITY AND TRANSCRIPTIONAL AND POSTTRANSCRIPTIONAL ACTIONS
Autore:
CHRISTENSON LK; MCALLISTER JM; MARTIN KO; JAVITT NB; OSBORNE TF; STRAUSS JF;
Indirizzi:
UNIV PENN,CTR RES REPROD & WOMENS HLTH,415 CURIE BLVD PHILADELPHIA PA19104 PENN STATE COLL MED,DEPT CELLULAR & MOL PHYSIOL HERSHEY PA 17033 NYU,MED CTR,DEPT MED NEW YORK NY 10016 UNIV CALIF IRVINE,DEPT MOL BIOL & BIOCHEM IRVINE CA 92717
Titolo Testata:
The Journal of biological chemistry
fascicolo: 46, volume: 273, anno: 1998,
pagine: 30729 - 30735
SICI:
0021-9258(1998)273:46<30729:OROSAR>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
LIPOPROTEIN RECEPTOR GENE; LEUCINE ZIPPER PROTEIN; HUMAN GRANULOSA-CELLS; STEROL 27-HYDROXYLASE; PROMOTER ACTIVITY; STAR GENE; CHOLESTEROL; PATHWAY; BINDING; 7-ALPHA-HYDROXYLATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
37
Recensione:
Indirizzi per estratti:
Citazione:
L.K. Christenson et al., "OXYSTEROL REGULATION OF STEROIDOGENIC ACUTE REGULATORY PROTEIN GENE-EXPRESSION - STRUCTURAL SPECIFICITY AND TRANSCRIPTIONAL AND POSTTRANSCRIPTIONAL ACTIONS", The Journal of biological chemistry, 273(46), 1998, pp. 30729-30735

Abstract

Oxysterols exert a major influence over cellular cholesterol homeostasis. We examined the effects of oxysterols on the expression of steroidogenic acute regulatory protein (StAR), which increases the delivery of cholesterol to sterol-metabolizing P450s in the mitochondria, 22(R)-hydroxycholesterol (22(R)-OHC), 25-OHC, and 27-OHC each increased steroidogenic factor-1 (SF-1)-mediated StAR gene transactivation by similar to 2-fold in CV-1 cells. In contrast, cholesterol, progesterone, and the 27-OHC metabolites, 27-OHC-5 beta-3-one and 7 alpha,27-OHC, had no effect. Unlike our findings in CV-1 cells, SF-1-dependent StAR promoter activity was not augmented by 27-OHC in COS-1 cells, Y-1 cells, EeWo choriocarcinoma cells, Chinese hamster ovary (CHO) cells, and human granulosa cells. Studies examining the metabolism of 27-OHC indicated that CV-1 cells formed a single polar metabolite, 3 beta-OH-5-cholestenoic acid from radiolabeled 27-OHC, However, this metabolite inhibited StAR promoter activity in CV-1, COS-1 and CHO cells. Because 7 alpha,27-OHC was unable to increase SF-1-dependent StAR promoter activity,we examined 27-OHC 7 alpha-hydroxylase in COS-1 and CHO cells. COS-1 cells contained high 7 alpha-hydroxylase activity, whereas the enzyme was undetectable in CHO cells. The hypothesis that oxysterols act in CV-1 cells to increase StAR promoter activity by reducing nuclear levels of sterol regulatory element binding protein was tested. This notionwas refuted when it was discovered that sterol regulatory element binding protein-1a is a potent activator of the StAR promoter in CV-1, COS-1, and human granulosa cells. Human granulosa and theca cells, whichexpress endogenous SF-1, contained more than 5-fold more StAR proteinfollowing addition of 27-OHC, whereas StAR mRNA levels remained unchanged. We conclude that 1) there are cell-specific effects of oxysterols on SF-1-dependent transactivation; 2) the ability to increase transactivation is limited to certain oxysterols; 3) there are cell-specificpathways of oxysterol metabolism; and 4) oxysterols elevate StAR protein levels through posttranscriptional actions.

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Documento generato il 23/09/20 alle ore 15:30:10