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Titolo:
Antisense oligonucleotides targeted to the p53 gene modulate liver regeneration in vivo
Autore:
Arora, V; Iversen, PL;
Indirizzi:
Univ Nebraska, Med Ctr, Dept Pharmacol, Omaha, NE USA Univ Nebraska OmahaNE USA raska, Med Ctr, Dept Pharmacol, Omaha, NE USA
Titolo Testata:
DRUG METABOLISM AND DISPOSITION
fascicolo: 2, volume: 28, anno: 2000,
pagine: 131 - 138
SICI:
0090-9556(200002)28:2<131:AOTTTP>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
CELL NUCLEAR ANTIGEN; PHOSPHOROTHIOATE OLIGODEOXYNUCLEOTIDE; INDUCIBLE CYTOCHROME-P-450; LIPID-PEROXIDATION; IN-VIVO; RATS; EXPRESSION; HEPATOCYTES; INHIBITION; TISSUES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: Iversen, PL AVI Biopharma Inc, 4575 SW Res Way,Suite 200, Corvallis, OR 97333 USA AVI Biopharma Inc 4575 SW Res Way,Suite 200 Corvallis OR USA 97333
Citazione:
V. Arora e P.L. Iversen, "Antisense oligonucleotides targeted to the p53 gene modulate liver regeneration in vivo", DRUG META D, 28(2), 2000, pp. 131-138

Abstract

The rapidly proliferating cells of the regenerating liver after partial hepatectomy (PH) present a reproducible in vivo model to study the functionalrole of the tumor suppressor gene p53. The present study uses the rat 70% PH model along with systemic administration of three different structural types of antisense oligonucleotides (ODNs) designed to suppress p53 expression. We tested the hypothesis that antisense ODNs can inhibit the expressionof p53, resulting in the loss of the G(1)-S cell cycle checkpoint and an altered pattern of liver regeneration. Intraperitoneal administration of 5 mg/kg/day antisense phosphorothioate ODN after 70% PH resulted in reduced expression of the p53 protein in the regenerating liver. There were concomitant increases in weight gain of remnant-regenerating liver and expression ofproliferating cell nuclear antigen and p21(waf-1) compared with either saline or 5 mg/kg/day mispaired phosphorothioate ODN treatment. Flow cytometric analysis of DNA content of isolated hepatocytes revealed a reduction in the G(0)/G(1) cell population and accumulation of cells with more than 4n DNA in antisense-treated rats. The regenerating livers had significantly diminished cytochrome P-450 (CYP) enzyme activities. Rats treated with p53 antisense ODNs, but not saline or mispair ODN controls, had significantly elevated CYP activities. These observations functionally link the expression of p53 with diminished expression of several CYP isoforms in the liver regeneration model.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/09/20 alle ore 01:03:15