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Titolo:
EFFICIENT ADENOVIRUS-MEDIATED ECTOPIC GENE-EXPRESSION OF HUMAN LIPOPROTEIN-LIPASE IN HUMAN HEPATIC (HEPG2) CELLS
Autore:
LIU GQ; EXCOFFON KJDA; BENOIT P; GINZINGER DG; MIAO L; EHRENBORG E; DUVERGER N; DENEFLE PP; HAYDEN MR; LEWIS MES;
Indirizzi:
UNIV BRITISH COLUMBIA,DEPT MED GENET,407-2125 E MALL,NCE BLDG VANCOUVER BC V6T 1Z4 CANADA UNIV BRITISH COLUMBIA,DEPT MED GENET VANCOUVER BC V6T 1Z4 CANADA GENCELL RHONE POULENC RORER F-94403 VITRY SUR SEINE FRANCE
Titolo Testata:
Human gene therapy
fascicolo: 2, volume: 8, anno: 1997,
pagine: 205 - 214
SICI:
1043-0342(1997)8:2<205:EAEGOH>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
MISSENSE MUTATION; RAT-LIVER; DEFICIENCY; INVIVO; ENZYME; CHOLESTEROL; METABOLISM; VECTORS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
36
Recensione:
Indirizzi per estratti:
Citazione:
G.Q. Liu et al., "EFFICIENT ADENOVIRUS-MEDIATED ECTOPIC GENE-EXPRESSION OF HUMAN LIPOPROTEIN-LIPASE IN HUMAN HEPATIC (HEPG2) CELLS", Human gene therapy, 8(2), 1997, pp. 205-214

Abstract

Gene therapy to deliver and express a corrective lipoprotein lipase (LPL) gene may improve the lipid profile and reduce the morbidity and potential atherogenic risk from hypertriglyceridemia and dyslipoproteinemia in patients with complete or partial LPL deficiency, We have usedan E1-/E3- adenoviral vector, with an RSV-driven human LPL cDNA expression cassette (Ad-RSV-LPL), to achieve high ectopic LPL gene expression in the human hepatoma cell line HepG2, an accepted hepatocellular model of lipoprotein metabolism, Ad-RSV-LPL transduction of HepG2 cellswith a multiplicity of infection (moi) between 12.5 and 100 yielded dose-dependent increments in LPL mass and activity, Peak levels of LPL protein of 2,032.1 +/- 274.5 ng/10(5) cells per mi (moi 100) correlated with increased activity of 92.7 +/- 22.6 mU/10(5) cells per mi relative to negligible LPL levels in Ad-RSV-LacZ (beta-galactosidase) controls. Exogenous LPL expression over a 5-day period peaked at day 3. Susceptibility to inhibition by 1 M NaCl and an anti-LPL monoclonal antibody confirmed that lipase activity was indeed derived from human LPL, Hydrolysis, by LPL-overexpressing HepG2 cells, of TG carried in very-low-density lipoprotein (VLDL) showed that greater than 50% of the triglycerides (TG) disappeared after 4 hr of incubation, These results were compatible with FPLC evidence of a marked reduction in VLDL-TG, These results provide strong in vitro evidence that adenoviral-mediated ectopic expression of the human LPL gene could render hepatic cells capable of VLDL catabolism and thus support the possibility for in vivo adenoviral vector-mediated liver-targeted LPL gene therapy.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 31/03/20 alle ore 18:02:44