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Titolo:
Effects of CYP7A1 overexpression on cholesterol and bile acid homeostasis
Autore:
Pandak, WM; Schwarz, C; Hylemon, PB; Mallonee, D; Valerie, K; Heuman, DM; Fisher, RA; Redford, K; Vlahcevic, ZR;
Indirizzi:
Vet Affairs Med Ctr, Div Gastroenterol 111N, Dept Med, Richmond, VA 23249 USA Vet Affairs Med Ctr Richmond VA USA 23249 ept Med, Richmond, VA 23249 USA Vet Affairs Med Ctr, Dept Microbiol, Richmond, VA 23249 USA Vet Affairs Med Ctr Richmond VA USA 23249 crobiol, Richmond, VA 23249 USA Vet Affairs Med Ctr, Dept Surg, Richmond, VA 23249 USA Vet Affairs Med Ctr Richmond VA USA 23249 pt Surg, Richmond, VA 23249 USA Virginia Commonwealth Univ, Richmond, VA 23249 USA Virginia Commonwealth Univ Richmond VA USA 23249 , Richmond, VA 23249 USA
Titolo Testata:
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
fascicolo: 4, volume: 281, anno: 2001,
pagine: G878 - G889
SICI:
0193-1857(200110)281:4<G878:EOCOOC>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
DENSITY-LIPOPROTEIN CHOLESTEROL; HMG-COA REDUCTASE; ACYL-COA; MESSENGER-RNA; 7-ALPHA-HYDROXYLASE GENE; STEROL 27-HYDROXYLASE; ACYLTRANSFERASE ACAT; DIETARY-CHOLESTEROL; MOLECULAR-CLONING; ADENOVIRUS TYPE-5;
Keywords:
acyl-coenzyme A : cholesterol acyltransferase; cholesterol 7 alpha-hydroxylase; 3-hydroxy-3-methyglutaryl-CoA reductase; low-density lipoprotein receptor; liver; neutral cholesterol ester hydrolase;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
57
Recensione:
Indirizzi per estratti:
Indirizzo: Pandak, WM Vet Affairs Med Ctr, Div Gastroenterol 111N, Dept Med, 1201 Broad Rock Rd,Richmond, VA 23249 USA Vet Affairs Med Ctr 1201 Broad Rock Rd Richmond VA USA 23249 SA
Citazione:
W.M. Pandak et al., "Effects of CYP7A1 overexpression on cholesterol and bile acid homeostasis", AM J P-GAST, 281(4), 2001, pp. G878-G889

Abstract

The initial and rate-limiting step in the classic pathway of bile acid biosynthesis is 7 alpha -hydroxylation of cholesterol, a reaction catalyzed bycholesterol 7 alpha -hydroxylase (CYP7A1). The effect of CYP7A1 overexpression on cholesterol homeostasis in human liver cells has not been examined. The specific aim of this study was to determine the effects of overexpression of CYP7A1 on key regulatory steps involved in hepatocellular cholesterol homeostasis, using primary human hepatocytes (PHH) and HepG2 cells. Overexpression of CYP7A1 in HepG2 cells and PHH was accomplished by using a recombinant adenovirus encoding a CYP7A1 cDNA (AdCMV-CYP7A1). CYP7A1 overexpression resulted in a marked activation of the classic pathway of bile acid biosynthesis in both PHH and HepG2 cells. In response, there was decreased HMG-CoA-reductase (HMGR) activity, decreased acyl CoA:cholesterol acyltransferase (ACAT) activity, increased cholesteryl ester hydrolase (CEH) activity,and increased low-density lipoprotein receptor (LDLR) mRNA expression. Changes observed in HMGR, ACAT, and CEH mRNA levels paralleled changes in enzyme specific activities. More specifically, LDLR expression, ACAT activity, and CEH activity appeared responsive to an increase in cholesterol degradation after increased CYP7A1 expression. Conversely, accumulation of the oxysterol 7 alpha -hydroxycholesterol in the microsomes after CYP7A1 overexpression was correlated with a decrease in HMGR activity.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/04/20 alle ore 03:54:59