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Titolo:
In vivo inhibition of cyclooxygenase-2 by a selective phosphorothioated oligonucleotide
Autore:
Khan, I; Al-Awadi, FM; Thomas, N;
Indirizzi:
Kuwait Univ, Fac Med, Dept Biochem, Kuwait, Kuwait Kuwait Univ Kuwait Kuwait t Univ, Fac Med, Dept Biochem, Kuwait, Kuwait
Titolo Testata:
ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT
fascicolo: 4, volume: 11, anno: 2001,
pagine: 199 - 207
SICI:
1087-2906(200108)11:4<199:IVIOCB>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
ANTISENSE OLIGONUCLEOTIDES; GASTROINTESTINAL TOXICITY; PROSTAGLANDIN E-2; MESSENGER-RNA; INFLAMMATION; MICE; RAT; ACID; EXPRESSION; ISOFORMS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
29
Recensione:
Indirizzi per estratti:
Indirizzo: Khan, I Kuwait Univ, Fac Med, Dept Biochem, Code 13110, Kuwait, Kuwait Kuwait Univ Code 13110 Kuwait Kuwait Code 13110, Kuwait, Kuwait
Citazione:
I. Khan et al., "In vivo inhibition of cyclooxygenase-2 by a selective phosphorothioated oligonucleotide", ANTISENSE N, 11(4), 2001, pp. 199-207

Abstract

Inhibition of cyclooxygenase-2 (cox-2) is considered to be anti-inflammatory, whereas inhibition of the constitutive isozyme cox-1 causes renal and gastrointestinal toxicity. Therefore, to achieve an optimal anti-inflammatory effect, an inhibitor should be cox-2 selective without inhibiting cox-1. For this purpose, 10 different cox-2-selective phosphorothioated oligonucleotides (S-oligos) were tested to inhibit the cox-2 enzyme selectively in vivo. An aqueous solution of these S-oligos (3 mg/kg body weight) was injected intraperitoneally (i.p.) into male Sprague-Dawley rats with colitis induced by trinitrobenzene sulfonic acid (TNBS). The colonic levels of cox-2 protein, mRNA, myeloperoxidase (MPO), and prostaglandin E-2 (PGE(2)) were increased significantly on day I and remained significantly elevated until day 7 post-TNBS administration, whereas cox-1 remained unaltered. Two S-oligos were found to be effective in reducing the level of cox-2 protein selectively without any effect on the cox-1. The effective S-oligo, but not the mismatched control oligo, reduced the tissue levels of PGE, and MPO activity significantly. The effective S-oligo reduced the level of cox-2 but not the cox-1 mRNA significantly, whereas a mismatched or a sense control oligo did not affect the levels of these isoforms. M-fold analysis demonstrated extensive secondary structure formation in the cox-2 mRNA. These findings demonstrate that only a few selected sites in the cox-2 target mRNA are accessible in vivo, probably because of the of secondary structures. Suppression of cox-2 protein, PGE(2), and MPO activity by the S-oligo might prove to be ananti-inflammatory property.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/09/20 alle ore 06:37:03