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Titolo:
MANIPULATION OF METALLOTHIONEIN EXPRESSION IN THE REGENERATING RAT-LIVER USING ANTISENSE OLIGONUCLEOTIDES
Autore:
ARORA V; IVERSEN PL; EBADI M;
Indirizzi:
UNIV NEBRASKA,COLL MED,DEPT PHARMACOL OMAHA NE 68198 UNIV NEBRASKA,COLL MED,DEPT PHARMACOL OMAHA NE 68198 AVI BIOPHARMA CORVALLIS OR 97333
Titolo Testata:
Biochemical and biophysical research communications
fascicolo: 3, volume: 246, anno: 1998,
pagine: 711 - 718
SICI:
0006-291X(1998)246:3<711:MOMEIT>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
ZINC-BINDING PROTEINS; I MESSENGER-RNA; PHOSPHOROTHIOATE OLIGODEOXYNUCLEOTIDE; TRANSCRIPTIONAL REGULATION; CELL-PROLIFERATION; LIPID-PEROXIDATION; PARA-NITROPHENOL; PHARMACOKINETICS; INDUCTION; TISSUES;
Keywords:
METALLOTHIONEIN; PARTIAL HEPATECTOMY AND LIVER REGENERATION; ANTISENSE OLIGONUCLEOTIDES; ACUTE PHASE PROTEIN AND OXIDATIVE STRESS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
65
Recensione:
Indirizzi per estratti:
Citazione:
V. Arora et al., "MANIPULATION OF METALLOTHIONEIN EXPRESSION IN THE REGENERATING RAT-LIVER USING ANTISENSE OLIGONUCLEOTIDES", Biochemical and biophysical research communications, 246(3), 1998, pp. 711-718

Abstract

Metallothioneins (MTs) are low molecular weight, zinc-binding proteins that by activating zinc metalloenzymes participate in the regulationof growth and development. The present study was designed to examine the roles of MTs in cell proliferation using an in vivo model of liverregeneration following partial hepatectomy (PH) in rats. The levels of MT-I and MT-II were studied with respect to regulation of proliferative potential, cell cycle checkpoint activity, and oxidative stress inthe rat PH model. We synthesized a 17-mer antisense phosphorothioate oligo deoxynucleotide (S-ODN), named aMT, complimentary to the start site of the MT-I mRNA sequence and an appropriate control. Both S-ODNs were administered intraperitoneally at the dose of 5 mg/kg following 70% PH. MT became induced 57.4 +/- 9.8-fold following PH and the said effect became attenuated dramatically following administration of aMT. In addition, PH rats treated with aMT exhibited decreased rate of liver regeneration as measured by expression of proliferating cell nuclearantigen and elevated cell cycle checkpoint activity as determined by expression of p53. The results of these studies suggest that MT isoforms with their high thiol contents do play an important role in cellular functions and especially during stressful states induced by a broad range of mediators generating free radicals. (C) 1998 Academic Press.

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Documento generato il 27/09/20 alle ore 07:11:05