TY - JOUR
T1 - Role of oxygen radicals generated by NADPH oxidase in apoptosis induced in human leukemia cells
AU - Hiraoka, Wakako
AU - Vazquez, Nancy
AU - Nieves-Neira, Wilberto
AU - Chanock, Stephen J.
AU - Pommier, Yves
PY - 1998/12/1
Y1 - 1998/12/1
N2 - 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-hydroxy-staurosporine. 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-κB) 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.
AB - 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-hydroxy-staurosporine. 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-κB) 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.
KW - Apoptosis
KW - Camptothecin
KW - Chronic granulomatous disease
KW - NADPH oxidase
KW - Reactive oxygen intermediates
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U2 - 10.1172/JCI3437
DO - 10.1172/JCI3437
M3 - Article
C2 - 9835621
AN - SCOPUS:0032421571
VL - 102
SP - 1961
EP - 1968
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 11
ER -