Involvement of pertussis toxin-sensitive mechanism in retinoic acid-induced differentiation of human leukemic HL-60 cells.
Retinoic acid-induced differentiation of human leukemic HL-60 cells is accompanied with the early induction of an ecto-enzyme of NAD+ glycohydrolase (NADase), which has recently been identified as human leukocyte cell surface antigen CD38 [Kontani, K. et al. (1993) J. Biol. Chem. 268, 16895-16898]. The terminal cell differentiation attendant upon the cell growth arrest was, but the early induction of CD38 NADase activity was not, inhibited by prior treatment of HL-60 cells with pertussis toxin, which catalyzed ADP-ribosylation of the membrane-bound alpha beta gamma-trimeric GTP-binding proteins. The prior treatment was, however, not essential for the toxin-induced inhibition of the cell differentiation; the inhibition by the addition of pertussis toxin was still observed even after retinoic acid-induced expression of CD38 antigen. This suggested that a pertussis toxin-sensitive mechanism was involved in a late process of cell differentiation. Indeed, HL-60 cells appeared to secrete a differentiation-supporting factor in response to retinoic acid, since the cell differentiation was accelerated and potentiated upon culture of the cells in a conditioned medium prepared from retinoic acid-treated cells. The action of the differentiation-supporting factor was destroyed by heating and markedly attenuated in pertussis toxin-pretreated HL-60 cells. Thus, the whole process of the retinoic acid-induced cell differentiation appeared to consist of two distinguishable periods in terms of sensitivity to pertussis toxin; the toxin-insensitive early period characterized by the induction of CD38 NADase activity and the toxin-sensitive late period in which the secretion of a differentiation-supporting factor might be involved.
Ohoka
Y
Y
Department of Life Science, Tokyo Institute of Technology, Yokohama.
Kontani
K
K
Iiri
T
T
Nishina
H
H
Katada
T
T
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD / Q000096:biosynthesis / Q000187:drug effects; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007938:Leukemia / Q000473:pathology*; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins / Q000378:metabolism; D037342:Pertussis Toxin; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D010566:Virulence Factors, Bordetella; D014212:Tretinoin; D037342:Pertussis Toxin; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1