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Titolo:
Overexpression of CYP27 in hepatic and extrahepatic cells: role in the regulation of cholesterol homeostasis
Autore:
Hall, E; Hylemon, P; Vlahcevic, Z; Mallonee, D; Valerie, K; Avadhani, N; Pandak, W;
Indirizzi:
Virginia Commonwealth Univ, Med Coll Virginia, Dept Med, Richmond, VA 23249 USA Virginia Commonwealth Univ Richmond VA USA 23249 , Richmond, VA 23249 USA Virginia Commonwealth Univ, Med Coll Virginia, Dept Microbiol & Immunol, Richmond, VA 23249 USA Virginia Commonwealth Univ Richmond VA USA 23249 , Richmond, VA 23249 USA McGuire Dept Vet Affairs Med Ctr, GI Sect 111 N, Richmond, VA 23249 USA McGuire Dept Vet Affairs Med Ctr Richmond VA USA 23249 mond, VA 23249 USA Univ Penn, Sch Vet Med, Dept Anim Biol, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 Anim Biol, Philadelphia, PA 19104 USA Univ Penn, Sch Vet Med, Mari Lowe Ctr Comparat Oncol, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 rat Oncol, Philadelphia, PA 19104 USA
Titolo Testata:
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
fascicolo: 1, volume: 281, anno: 2001,
pagine: G293 - G301
SICI:
0193-1857(200107)281:1<G293:OOCIHA>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
BILE-ACID BIOSYNTHESIS; STEROL 27-HYDROXYLASE GENE; CULTURED RAT HEPATOCYTES; HMG-COA REDUCTASE; MESSENGER-RNA; CEREBROTENDINOUS XANTHOMATOSIS; TRANSCRIPTIONAL ACTIVITY; CHOLIC-ACID; ACYL-COA; LIVER;
Keywords:
liver; bile acid; 3-hydroxy-3-methylglutaryl CoA reductase; Hep G2 cells; acyl CoA-cholesterol acyltransferase; cholesteryl ester hydrolase; adenovirus; gene;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: Pandak, W McGuire Dept Vet Affairs Med Ctr, GI Sect 111 N, 1201 Broad RockBlvd, Richmond, VA 23249 USA McGuire Dept Vet Affairs Med Ctr 1201 Broad Rock Blvd Richmond VA USA 23249
Citazione:
E. Hall et al., "Overexpression of CYP27 in hepatic and extrahepatic cells: role in the regulation of cholesterol homeostasis", AM J P-GAST, 281(1), 2001, pp. G293-G301

Abstract

In the liver, sterol 27-hydroxylase (CYP27) participates in the classic and alternative pathways of bile acid biosynthesis from cholesterol (Chol). In extrahepatic tissues, CYP27 converts intracellular Chol to 27-hydroxycholesterol (27OH-Chol), which may regulate the activity of 3-hydroxy-3-methylglutaryl CoA reductase (HMG-CoA-R). This study attempts to better define therole of CYP27 in the maintenance of Chol homeostasis in hepatic and extrahepatic cells by overexpressing CYP27 in Hep G2 cells and Chinese hamster ovary (CHO) cells through infection with a replication-defective recombinant adenovirus encoding for CMV-CYP27. After infection, CYP27 mRNA and protein levels increased dramatically. CYP27 specific activity also increased two- to fourfold in infected cells (P less than or equal to 0.02), with a markedincrease in conversion of [C-14]Chol to [C-14]27OH-Chol (similar to 150%; P less than or equal to 0.01). Accumulation of 27OH-Chol in CHO cells was associated with a 50% decrease in HMG-CoA-R specific activity (P less than or equal to 0.02). In infected Hep G2 cells, the significant increase in bile acid synthesis (46%; P less than or equal to 0.006), which prevented the accumulation of intracellular 27OH-Chol, resulted in increased HMG-CoA-R activity (183%; P less than or equal to 0.02). Overexpression of CYP27 in HepG2 cells also increased acyl CoA-cholesterol acyltransferase (71%, P less than or equal to 0.02) and decreased cholesteryl ester hydrolase (55%, P less than or equal to 0.02). In conclusion, CYP27 generates different physiological responses depending on cell type and presence or absence of bile acid biosynthetic pathways.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/04/20 alle ore 13:14:10