Role of oxygen radicals generated by NADPH oxidase in apoptosis induced in human leukemia cells.
J Clin Invest
; 102(11): 1961-8, 1998 Dec 01.
Article
en En
| MEDLINE
| ID: mdl-9835621
ABSTRACT
We have used a human leukemia cell line that, after homologous recombination knockout of the gp91-phox subunit of the phagocyte respiratory-burst oxidase cytochrome b-558, mimics chronic granulomatous disease (X-CGD) to study the role of oxygen radicals in apoptosis. Camptothecin (CPT), a topoisomerase I inhibitor, induced significantly more apoptosis in PLB-985 cells than in X-CGD cells. Sensitivity to CPT was enhanced after neutrophilic differentiation, but was lost after monocytic differentiation. No difference between the two cell lines was observed after treatment with other apoptosis inducers, including etoposide, ultraviolet radiation, ionizing radiation, hydrogen peroxide, or 7-hydroxystaurosporine. After granulocytic differentiation of both cell lines, CPT still induced apoptosis, suggesting independence from replication in fully differentiated and growth-arrested cells. Pyrrolidine dithiocarbamate (an antioxidant inhibitor of NF-kappaB) and catalase partially inhibited CPT-induced DNA fragmentation in granulocytic-differentiated PLB-985 cells, but had no effect in X-CGD cells. Flow cytometry analysis revealed that reactive oxygen intermediates were generated in CPT-treated PLB-985 cells. These data indicate that oxygen radicals generated by NADPH oxidase may contribute directly or indirectly to CPT-induced apoptosis in human leukemia and in neutrophilic-differentiated cells.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Camptotecina
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Glicoproteínas de Membrana
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Leucemia
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Especies Reactivas de Oxígeno
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Apoptosis
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NADPH Oxidasas
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Proteínas de Neoplasias
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Antineoplásicos Fitogénicos
Límite:
Humans
Idioma:
En
Revista:
J Clin Invest
Año:
1998
Tipo del documento:
Article
País de afiliación:
Estados Unidos