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Titolo:
Cu/Zn superoxide dismutase plays a role in angiogenesis
Autore:
Marikovsky, M; Nevo, N; Vadai, E; Harris-Cerruti, C;
Indirizzi:
Hebrew Univ Jerusalem, Fac Agr, Dept Anim Sci, IL-76100 Rehovot, Israel Hebrew Univ Jerusalem Rehovot Israel IL-76100 , IL-76100 Rehovot, Israel Weizmann Inst Sci, Dept Regulat Biol, IL-76100 Rehovot, Israel Weizmann Inst Sci Rehovot Israel IL-76100 Biol, IL-76100 Rehovot, Israel Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel Weizmann Inst Sci Rehovot Israel IL-76100 unol, IL-76100 Rehovot, Israel Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel Weizmann Inst Sci Rehovot Israel IL-76100 enet, IL-76100 Rehovot, Israel
Titolo Testata:
INTERNATIONAL JOURNAL OF CANCER
fascicolo: 1, volume: 97, anno: 2002,
pagine: 34 - 41
SICI:
0020-7136(20020101)97:1<34:CSDPAR>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
ENDOTHELIAL GROWTH-FACTOR; FREE-RADICAL GENERATION; LEWIS LUNG-CARCINOMA; TUMOR-GROWTH; XANTHINE-OXIDASE; TRANSGENIC MICE; OXYGEN RADICALS; NITRIC-OXIDE; WOUND FLUID; CELL-DEATH;
Keywords:
Cu/Zn superoxide dismutase; reactive oxygen species; disulfiram; endothelial; transgeric mice;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
69
Recensione:
Indirizzi per estratti:
Indirizzo: Marikovsky, M Hebrew Univ Jerusalem, Fac Agr, Dept Anim Sci, IL-76100 Rehovot, Israel Hebrew Univ Jerusalem Rehovot Israel IL-76100 ovot, Israel
Citazione:
M. Marikovsky et al., "Cu/Zn superoxide dismutase plays a role in angiogenesis", INT J CANC, 97(1), 2002, pp. 34-41

Abstract

Endothelial cells produce oxygen radicals spontaneously and this process is augmented by hypoxia/reoxygenation. Cu/Zn superoxide dismutase (SOD-1) isan important enzyme in cellular oxygen metabolism. To determine whether alterations in SOD-1 activity affect angiogenesis we used transgenic SOD-1 (Tg-SOD) mice with elevated level of SOD-1. Angiogenesis induced subcutaneously by bFGF in Tg-SOD mice was 3-fold higher than in control non-transgenic (ntg) mice. Oral administration of disulfiram (DSF), an inhibitor of SOD-1,inhibited angiogenesis in Tg-SOD mice as well as in CD I nude mice. Effects of DSF on cultured cells were also tested. Application of DSF to culturedbovine capillary endothelial (BCE) cells caused inhibition of DNA synthesis and induction of apoptosis. These effects were prevented by addition of antioxidants, further indicating involvement of reactive oxygen species. DSFalso reduced the level of glutathione and the production of H2O2 in BCE cells. Moreover, PC12-SOD cells with elevated SOD-1 were less sensitive to DSF treatment then control cells. These data indicate that the effects of DSFare mediated by inhibition of SOD-1 activity. Tumor development is known to largely depend on angiogenesis. We found that oral administration of DSF to mice caused significant inhibition of C6 glioma tumor development and marked reduction (by 10-19-fold) in metastatic growth of Lewis lung carcinoma. The data suggest a role for SOD-1 in angiogenesis, establish DSF as a potential inhibitor of angiogenesis and raise the possibility that attenuatingSOD-1 activity may be important in treatment of angiogenesis-dependent pathologies. (C) 2002 Wiley-Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 07/04/20 alle ore 23:05:12