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Titolo:
Redox regulation of adenovirus-induced AP-1 activation by overexpression of manganese-containing superoxide dismutase
Autore:
Zhang, HJ; Drake, VJ; Xu, LJ; Hu, JF; Domann, FE; Oberley, LW; Kregel, KC;
Indirizzi:
Univ Iowa, Integrat Physiol Lab, Dept Exercise Sci, Iowa City, IA 52242 USA Univ Iowa Iowa City IA USA 52242 pt Exercise Sci, Iowa City, IA 52242 USA Univ Iowa, Dept Radiat Oncol, Free Rad & Radiat Biol Program, Iowa City, IA 52242 USA Univ Iowa Iowa City IA USA 52242 at Biol Program, Iowa City, IA 52242 USA
Titolo Testata:
JOURNAL OF VIROLOGY
fascicolo: 1, volume: 76, anno: 2002,
pagine: 355 - 363
SICI:
0022-538X(200201)76:1<355:RROAAA>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
NF-KAPPA-B; MEDIATED GENE-TRANSFER; DNA-BINDING ACTIVITY; HEPATOCYTES IN-VIVO; HEAT-SHOCK; MOUSE HEPATOCYTES; CELL ACTIVATION; EXPRESSION; LIVER; REF-1;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Kregel, KC Univ Iowa, Integrat Physiol Lab, Dept Exercise Sci, 532 FH, Iowa City, IA 52242 USA Univ Iowa 532 FH Iowa City IA USA 52242 Iowa City, IA 52242 USA
Citazione:
H.J. Zhang et al., "Redox regulation of adenovirus-induced AP-1 activation by overexpression of manganese-containing superoxide dismutase", J VIROLOGY, 76(1), 2002, pp. 355-363

Abstract

Adenovirus gene therapy is a promising tool in the clinical treatment of many genetic and acquired diseases. However, it has also caused pathogenic effects in organs such as the liver. The redox-sensitive transcription factors AP-1 and NF-kappaB have been implicated in these effects. To study the mechanisms of adenovirus-mediated AP-1 and NF-kappaB activation and the possible involvement of oxidative stress in adenovirus transduction, rats were injected with either replication-defective recombinant adenovirus with DNA containing the cytomegalovirus promoter region only (AdCMV), adenovirus containing human manganese-containing superoxide dismutase (MnSOD) cDNA (AdMnSOD), or vehicle. Compared to vehicle and AdCMV transduction, MnSOD gene transfer yielded a fivefold increase in liver MnSOD activity 7 days postinjection. Gel shift assay showed that AdCMV transduction induced DNA binding activity for AP-1 but not NF-kappaB. MnSOD overexpression abolished this activation. Western blotting analysis of c-Fos and c-Jun suggested that up-regulation of c-fos and c-jun gene expression does not directly contribute to the induction of AP-1 activation. Glutathione/ glutathione disulfide ratios were decreased by adenovirus transduction and restored by MnSOD overexpression. The AP-1 binding activity that was induced by AdCMV was decreased by immunoprecipitation of Ref-1 protein. Ref-1 involvement was confirmed by restoration of AP-1 binding activity after the immunoprecipitated Ref-1 proteinhad been added back. AP-1 DNA binding activity was also elevated in control and AdMnSOD-injected rats after addition of the immunoprecipitated Ref-1 protein. These data indicate that cellular transduction by recombinant adenovirus stimulates AP-1 DNA binding activity. Furthermore, our results suggest that MnSOD overexpression decreases AP-I DNA binding activity by regulating intracellular redox status, with the possible involvement of Ref-1 in this redox-sensitive pathway.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/02/20 alle ore 13:56:25