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Titolo:
TRANSCRIPTIONAL REGULATION OF THE HUMAN CHOLESTEROL 7-ALPHA-HYDROXYLASE GENE (CYP7A) IN HEPG2 CELLS
Autore:
WANG DP; STROUP D; MARRAPODI M; CRESTANI M; GALLI G; CHIANG JYL;
Indirizzi:
NE OHIO UNIV,COLL MED,DEPT BIOCHEM & MOL PATHOL ROOTSTOWN OH 44272 NE OHIO UNIV,COLL MED,DEPT BIOCHEM & MOL PATHOL ROOTSTOWN OH 44272 UNIV MILAN,INST PHARMACOL SCI MILAN ITALY
Titolo Testata:
Journal of lipid research
fascicolo: 9, volume: 37, anno: 1996,
pagine: 1831 - 1841
SICI:
0022-2275(1996)37:9<1831:TROTHC>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
BILE-ACID SYNTHESIS; MESSENGER-RNA LEVELS; HORMONE RECEPTOR-BETA; PROTEIN-KINASE-C; THYROID-HORMONE; RAT HEPATOCYTES; HYPOPHYSECTOMIZED RATS; HYDROXYLASE GENE; DOWN-REGULATION; LIGAND-BINDING;
Keywords:
CYTOCHROME P450; HORMONAL REGULATION; GENE TRANSCRIPTION; NUCLEAR RECEPTORS; HEPATOCYTE NUCLEAR FACTOR; HNF 3-ALPHA; PHORBOL ESTERS; THYROID HORMONES; GLUCOCORTICOID; INSULIN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
40
Recensione:
Indirizzi per estratti:
Citazione:
D.P. Wang et al., "TRANSCRIPTIONAL REGULATION OF THE HUMAN CHOLESTEROL 7-ALPHA-HYDROXYLASE GENE (CYP7A) IN HEPG2 CELLS", Journal of lipid research, 37(9), 1996, pp. 1831-1841

Abstract

A stable HepG2 cell line harboring a human cholesterol 7 alpha-hydroxylase (CYP7A) minigene/luciferase reporter gene construct was selectedfor studying transcriptional regulation of CYP7A gene promoter. Insulin and phorbol 12-myristate-13-acetate (PMA) strongly repressed the promoter activity as measured with luciferase activity expressed in the cells. The promoter activity of the 5' progressive deletion/luciferasereporter gene constructs was studied in a transient transfection assay in HepG2 cells. PMA re presses the promoter activity and the response elements were localized in the -184/-151 and -134/-81 regions. Insulin also represses the promoter activity and response element was mapped in the -298/-81 region. Surprisingly, glucocorticoid receptor (GR) strongly inhibited promoter activity in the presence of dexamethasone, and response elements were localized in the -298/-151 and the -150/+24regions. Thyroid hormone receptor also repressed promoter activity and response elements were localized in the -150/+24 and upstream regions. Cotransfection of CYP7A chimeric constructs with an expression vector carrying liver-enriched transcription factor HNF3 alpha stimulated the reporter gene activity, but cotransfection with GR plasmid interfered with the HNF3 alpha-stimulated activity possibly through competition for binding to overlapping GR/HNF3 binding sites.jlr Thus, human cholesterol 7 alpha-hydroxylase gene promoter is strongly repressed by insulin, PMA, and steroid/thyroid hormones and results in the low levelof cholesterol 7 alpha-hydroxylase expression in the human liver.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/09/20 alle ore 11:47:09