Role of catalase in monocytic differentiation of U937 cells by TPA: hydrogen peroxide as a second messenger

Human promonocytic cell line U937 cells can be induced to differentiate into macrophages by treatment with 12- O -tetradecanoylphorbol-13-acetate (TPA). TPA treatment induced the expression of the monocytic differentiation markers CD11b and CD36, with concomitant morphological changes. Moreover, TPA...

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Veröffentlicht in:Leukemia 2009-04, Vol.23 (4), p.761-769
Hauptverfasser: Yamamoto, T, Sakaguchi, N, Hachiya, M, Nakayama, F, Yamakawa, M, Akashi, M
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container_issue 4
container_start_page 761
container_title Leukemia
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creator Yamamoto, T
Sakaguchi, N
Hachiya, M
Nakayama, F
Yamakawa, M
Akashi, M
description Human promonocytic cell line U937 cells can be induced to differentiate into macrophages by treatment with 12- O -tetradecanoylphorbol-13-acetate (TPA). TPA treatment induced the expression of the monocytic differentiation markers CD11b and CD36, with concomitant morphological changes. Moreover, TPA enhanced reactive oxygen species (ROS) generation in these cells, and phagocytic ability was also stimulated during differentiation. The antioxidant agent N -acetyl- L -cysteine inhibited the TPA-induced differentiation of U937 cells. TPA treatment decreased the expression level of catalase, which catalyzes the decomposition of hydrogen peroxide (H 2 O 2 ) to H 2 O and O 2 . In contrast, TPA increased the level of manganese superoxide dismutase, which catalyzes the dismutation of superoxide into H 2 O 2 and O 2 without affecting the levels of copper-zinc superoxide dismutase or glutathione peroxidase 1, which removes H 2 O 2 using glutathione as substrate. Treatment of U937 cells with catalase inhibited the enhancement of ROS generation induced by TPA, and blocked the TPA-induced differentiation of U937 cells. Human promyelocytic cell line HL60 cells were also induced to differentiate into macrophages by TPA. However, HP100-1 cells, its variant cell line overexpressing catalase, were resistant to TPA-induced differentiation. Our results suggest that catalase inhibits monocytic differentiation by TPA; the decrease in catalase level and the accumulation of H 2 O 2 are significant events for monocyte/macrophage differentiation by TPA.
doi_str_mv 10.1038/leu.2008.353
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subjects 12-O-Tetradecanoylphorbol-13-acetate
Acetic acid
Acetylcysteine
Antioxidants
Biological and medical sciences
Cancer Research
Catalase
Catalase - analysis
Catalase - physiology
CD11b antigen
CD36 antigen
Cell differentiation
Cell Differentiation - drug effects
Cell growth
Critical Care Medicine
Differentiation
Emergency medical care
Glutathione
Glutathione peroxidase
Hematologic and hematopoietic diseases
Hematology
Humans
Hydrogen Peroxide
Intensive
Internal Medicine
Leukemia
Macrophages
Macrophages - cytology
Manganese
Medical research
Medical sciences
Medicine
Medicine & Public Health
Monocytes
Monocytes - cytology
Oncology
original-article
Oxidation
Peroxidase
Phagocytes
Phorbol esters
Physiological aspects
Polyclonal antibodies
Radiation
Reactive oxygen species
Reactive Oxygen Species - metabolism
Roles
Second Messenger Systems
Stem cells
Superoxide dismutase
Superoxide Dismutase - analysis
Tetradecanoylphorbol Acetate - pharmacology
U937 Cells
title Role of catalase in monocytic differentiation of U937 cells by TPA: hydrogen peroxide as a second messenger
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