Up-regulation of CD13/aminopeptidase N induced by phorbol ester is involved in redox regulation and tumor necrosis factor alpha production in HL-60 cells.
Here, we demonstrate the possible involvement of oxidative stress in altered CD13/aminopeptidase N (APN) expression during myeloid cell differentiation induced by TPA. In flow cytometrical analysis, CD13/APN protein was constitutively expressed in HL-60 cells. When the cells were treated with TPA, CD13/APN expression was up-regulated with increased intracellular peroxides and a morphological change into macrophage-like cells. This increase in CD13/APN expression was suppressed by treatment with N-acetylcysteine. Transfection of Mn-superoxide dismutase (MnSOD) gene to the cells also suppressed the up-regulated CD13/APN expression. Furthermore, a neutralizing antibody to TNFalpha partially blocked this up-regulation. These results indicate that the change in intracellular redox state could be involved in the up-regulation of CD13/APN expression during TPA-induced differentiation of HL-60 cells, suggesting that TNFalpha may serve as, at least, one of the signals stimulated by TPA.
Division of Life Science, Graduate School of Science and Technology, Kobe University, Japan.
Yutaka
Y
Hatanaka
Hitoshi
H
Ashida
Kaoru
K
Hashizume
Itsuko
I
Fukuda
Takashi
T
Sano
Yukihiro
Y
Yamaguchi
Takeshi
T
Endo
Yoichi
Y
Tani
Keiichiro
K
Suzukia
Gen-ichi
G
Danno
D000111:Acetylcysteine / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D018826:CD13 Antigens / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016207:Cytokines / Q000502:physiology; D018922:HL-60 Cells; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology; D010084:Oxidation-Reduction; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000235:genetics / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013859:Thiocarbamates / Q000494:pharmacology; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D015854:Up-Regulation
D000975:Antioxidants; D016207:Cytokines; D018836:Inflammation Mediators; D013859:Thiocarbamates; D014409:Tumor Necrosis Factor-alpha; C066229:prolinedithiocarbamate; D011392:Proline; D013482:Superoxide Dismutase; D018826:CD13 Antigens; D013755:Tetradecanoylphorbol Acetate; D000111:Acetylcysteine