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Titolo:
Involvement of CD95-independent caspase 8 activation in arsenic trioxide-induced apoptosis
Autore:
Kitamura, K; Minami, Y; Yamamoto, K; Akao, Y; Kiyoi, H; Saito, H; Naoe, T;
Indirizzi:
Nagoya Univ, Sch Med, Dept Infect Dis, Showa Ku, Nagoya, Aichi 4668550, Japan Nagoya Univ Nagoya Aichi Japan 4668550 a Ku, Nagoya, Aichi 4668550, Japan Nagoya Univ, Sch Med, Dept Internal Med 1, Showa Ku, Nagoya, Aichi 4668550, Japan Nagoya Univ Nagoya Aichi Japan 4668550 a Ku, Nagoya, Aichi 4668550, Japan Gifu Int Inst Biotechnol, Gifu, Japan Gifu Int Inst Biotechnol Gifu Japan fu Int Inst Biotechnol, Gifu, Japan
Titolo Testata:
LEUKEMIA
fascicolo: 10, volume: 14, anno: 2000,
pagine: 1743 - 1750
SICI:
0887-6924(200010)14:10<1743:IOCC8A>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACUTE PROMYELOCYTIC LEUKEMIA; PML-RAR-ALPHA; MITOCHONDRIAL PERMEABILITY TRANSITION; CYTOCHROME-C RELEASE; RESISTANT NB4 CELLS; RETINOIC ACID; DOWN-REGULATION; IN-VITRO; SIGNAL-TRANSDUCTION; GROWTH-INHIBITION;
Keywords:
acute promyelocytic leukemia; apoptosis; arsenic trioxide; caspase 8;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
60
Recensione:
Indirizzi per estratti:
Indirizzo: Naoe, T Nagoya Univ, Sch Med, Dept Infect Dis, Showa Ku, 65 Tsurumai Cho, Nagoya, Aichi 4668550, Japan Nagoya Univ 65 Tsurumai Cho Nagoya Aichi Japan4668550 8550, Japan
Citazione:
K. Kitamura et al., "Involvement of CD95-independent caspase 8 activation in arsenic trioxide-induced apoptosis", LEUKEMIA, 14(10), 2000, pp. 1743-1750

Abstract

Arsenic trioxide (As2O3)-treatment is effective in acute promyelocytic leukemia (APL) patients with t(15;17). Clinically achievable concentrations ofAs2O3 induce apoptosis in NB4, an APL cell line, in vitro. Here, to study the mechanism of As2O3-induced apoptosis, we established an As2O3-resistantsubline, NB4/As. Growth of NB4/As was inhibited by 50% after 2 day-treatment (IC50) at 1.6 mu M As2O3, whereas IC50 of NB4 was 0.3 mu M. Degradation of PML-RAR alpha and change of the PML-subcellular localization were similarly induced by As2O3 in NB4 and NB4/As, suggesting that their contribution to apoptosis is small. Treatment with 1 mu M As2O3 induced the activation of caspase 3 as well as a loss of mitochondrial transmembrane potential (Delta Psi m) in NB4 but not in NB4/As. Caspase 8 and Bid were also activated by As2O3 in NB4 but not in NB4/As. In NB4, an inhibitor of caspase 8 blockednot only the activation of caspase 3 but also the loss of Delta Psi m. Neither cell line expressed CD95/Fas, and agonistic anti-Fas antibody (CH-11) failed to cause apoptosis. Neither antagonistic anti-CD95/Fas antibody nor anti-fas ligand antibodies influenced the As2O3-induced apoptosis. NB4/As had a higher concentration of intracellular glutathione (GSH) than NB4 (96 vs 32 nmol/mg). Reduction of the GSH level by buthionine sulfoxide (BSO) completely restored the sensitivity to As2O3 in NB4/As. Furthermore, caspase activation and the loss of Delta Psi m were recovered by combination treatment with BSO. These findings suggest that the As2O3 treatment activates caspase 8 in a CD95-independent but GSH concentration-dependent manner. In combination with BSO, As2O3 might be applied to therapy of leukemia/cancers which are insensitive to the clinically achievable concentrations of As2O3.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/11/20 alle ore 00:52:44