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Titolo:
ETHANOL DOWN-REGULATES THE TRANSCRIPTION OF MICROSOMAL TRIGLYCERIDE TRANSFER PROTEIN GENE
Autore:
LIN MCM; LI JJ; WANG EJ; PRINCLER GL; KAUFFMAN FC; KUNG HF;
Indirizzi:
UNIV MED & DENT NEW JERSEY,SCH OSTEOPATH MED,DEPT CELL BIOL STRATFORDNJ 08084 NCI,FREDERICK CANC RES & DEV CTR,LAB BIOCHEM PHYSIOL,NIH FREDERICK MD21702 RUTGERS STATE UNIV,DEPT PHARMACOL & TOXICOL PISCATAWAY NJ 08855
Titolo Testata:
The FASEB journal
fascicolo: 13, volume: 11, anno: 1997,
pagine: 1145 - 1152
SICI:
0892-6638(1997)11:13<1145:EDTTOM>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
MODERATE ALCOHOL-CONSUMPTION; B-CONTAINING LIPOPROTEINS; CORONARY HEART-DISEASE; APOLIPOPROTEIN-B; HEPG2 CELLS; SECRETION; ABETALIPOPROTEINEMIA; EXPRESSION; RISK; MEN;
Keywords:
MTP; GENE EXPRESSION; HEPG2; RATS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
35
Recensione:
Indirizzi per estratti:
Citazione:
M.C.M. Lin et al., "ETHANOL DOWN-REGULATES THE TRANSCRIPTION OF MICROSOMAL TRIGLYCERIDE TRANSFER PROTEIN GENE", The FASEB journal, 11(13), 1997, pp. 1145-1152

Abstract

Microsomal triglyceride transfer protein (MTP) plays a central role in the assembly and secretion of apoB-containing lipoproteins. In this study, we investigated the effect of ethanol on the expression of the large subunit of MTP in a human liver hepatoma cell line, the HepG2 cells, Exposure of HepG2 cells to low concentrations of ethanol reduced MTP mRNA levels in a concentration-and time-dependent manner, The level of MTP mRNA decreased significantly (P < 0.05, -26% relative to pretreatment control) when the concentration of ethanol in the culture medium was 50 ppm (0.005%, v/v), Maximal suppression (-50%) was observed at 100 ppm ethanol; the MTP mRNA levels remained at 50% of control when the ethanol concentration was raised to 10,000 ppm, Furthermore, a 10-day ethanol treatment caused a significant 50% decrease in the MTP activity and apoB secretion rate in HepG2 cells. To investigate the molecular mechanisms underlying this phenomenon, we examined the effect of ethanol on the promoter activity of the MTP gene. Transient transfection analysis of human MTP promoter-driven luciferase gene expression showed that ethanol down-regulates MTP promoter activity in a manner parallel to that observed for mRNA levels, Deletion analysis suggested that the MTP promoter sequence contains a negative ethanol response element -612 to -142 bp upstream of the transcription start site, To evaluate the in vivo relevance of the effect of ethanol on MTP mRNA levels, rats were given a single oral dose of ethanol, with hepatic and intestinal MTP mRNA measured 3 h after dosing, Rats receiving 1 or 3 g/kgof ethanol exhibited substantially lower hepatic and intestinal MTP mRNA levels, Taken together, these results strongly suggest that ethanol can modulate the secretion of apoB-containing lipoproteins by down-regulating the expression of MTP large subunit, primarily through inhibiting the transcription of the MTP gene.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/01/20 alle ore 15:37:45