Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
TISSUE-SPECIFIC EXPRESSION AND CHOLESTEROL REGULATION OF ACYLCOENZYMEA-CHOLESTEROL ACYLTRANSFERASE (ACAT) IN MICE - MOLECULAR-CLONING OF MOUSE ACAT CDNA, CHROMOSOMAL LOCALIZATION, AND REGULATION OF ACAT IN-VIVO AND IN-VITRO
Autore:
UELMEN PJ; OKA K; SULLIVAN M; CHANG CCY; CHANG TY; CHAN L;
Indirizzi:
BAYLOR COLL MED,DEPT CELL BIOL,1 BAYLOR PLAZA HOUSTON TX 77030 BAYLOR COLL MED,DEPT CELL BIOL HOUSTON TX 77030 BAYLOR COLL MED,DEPT MED HOUSTON TX 77030 DARTMOUTH COLL SCH MED,DEPT BIOCHEM HANOVER NH 03755
Titolo Testata:
The Journal of biological chemistry
fascicolo: 44, volume: 270, anno: 1995,
pagine: 26192 - 26201
SICI:
0021-9258(1995)270:44<26192:TEACRO>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACYL-COENZYME-A; DETERMINING ATHEROSCLEROSIS SUSCEPTIBILITY; APO-B SECRETION; PREPUTIAL GLAND; DENSITY LIPOPROTEIN; ESTER SYNTHESIS; CELLS; COA; RAT; LIVER;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
46
Recensione:
Indirizzi per estratti:
Citazione:
P.J. Uelmen et al., "TISSUE-SPECIFIC EXPRESSION AND CHOLESTEROL REGULATION OF ACYLCOENZYMEA-CHOLESTEROL ACYLTRANSFERASE (ACAT) IN MICE - MOLECULAR-CLONING OF MOUSE ACAT CDNA, CHROMOSOMAL LOCALIZATION, AND REGULATION OF ACAT IN-VIVO AND IN-VITRO", The Journal of biological chemistry, 270(44), 1995, pp. 26192-26201

Abstract

Acyl coenzyme Archolesterol acyltransferase (ACAT) catalyzes the esterification of cholesterol with long chain fatty acids and is believed to play an important part in the development of atherosclerotic lesions. To facilitate the study of ACAT's role in this process, we have used the human ACAT K1 clone previously described (Chang, C. C. Y., Huh, H. Y., Cadigan, H. M, and Chang, T, Y. (1993) J. Biol. Chem. 268, 20747-20755) to isolate mouse ACAT cDNA from a liver cDNA library. The 3.7-kilobase cDNA clone isolated contains a 1620-base pair open reading frame which encodes a protein of 540 amino acids. The predicted mouse ACAT protein is 87% identical to the protein product of human ACAT HI and shares many of the same secondary structural features, including two transmembrane domains, a leucine heptad motif consistent with dimer or multimer formation, and five regions homologous to the ''signature sequences'' found in other enzymes that catalyze acyl adenylation followed by acyl thioester formation and acyl transfer. Using the cDNA as a hybridization probe, we mapped the gene encoding mouse ACAT to chromosome 1 in a region syntenic to human chromosome 1 where the ACAT geneis located. Northern blot analysis and RNase protection assays of mouse tissues revealed that ACAT mRNA is expressed most highly in the adrenal gland, ovary, and preputial gland and is least abundant in skeletal muscle, adipose tissue, heart, and brain. To study the dietary regulation of ACAT mRNA expression in mouse tissues, we fed C57BL/6J mice a high-fat, high-cholesterol (HF/HC) atherogenic diet for 3 weeks and measured ACAT mRNA levels in various tissues by RNase protection, The HF/HC diet had little effect on ACAT mRNA levels in the small intestine, aorta, adrenal, or peritoneal macrophages, whereas hepatic ACAT mRNA levels were doubled in mice fed the atherogenic diet, ACAT activity in liver microsomes was similarly increased in cholesterol-fed mice, suggesting that mouse ACAT is regulated at least in part at the level of mRNA abundance. Additionally, a significant positive correlation wasobserved between ACAT activity and microsomal free cholesterol levelsin chow- and cholesterol-fed mice, supporting the concept of cholesterol availability as a regulator of ACAT. To further investigate the regulation of ACAT activity under controlled conditions, ACAT-deficient Chinese hamster ovary cells were stably transfected with the mouse ACAT cDNA clone driven by a cytomegalovirus promoter, Two transfected Chinese hamster ovary cell lines that expressed the mouse ACAT transgene regained the ability to esterify cholesterol. Cholesterol esterification activity in both of these cell lines was further increased by exposure of these cells to low density lipoprotein, Thus we have demonstrated that mouse ACAT expression in vivo and in vitro is regulated by at least two mechanisms: control of mRNA abundance and post-transcriptional regulation of the enzyme activity, probably by cholesterol availability.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/04/20 alle ore 20:08:58