This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by INABA, M. Articles by MORII, H. Search for Related Content PubMed PubMed Citation Articles by INABA, M. Articles by MORII, H.

Polyamines in l, 25-Dihydroxycholecalciferol-Induced Differentiation of Human Promyelocytic Leukemia Cells, HL-60

Second Department of Internal Medicine Osaka City University Medical School 1-5-7, Asahi-machi, Abenoku, Osaka 545, Japan
Departments of Biochemistry Osaka City University Medical School 1-5-7, Asahi-machi, Abenoku, Osaka 545, Japan
Departments of Pathology Osaka City University Medical School 1-5-7, Asahi-machi, Abenoku, Osaka 545, Japan
Sumitomo Pharmaceuticals Co. Ltd Takarazuka, Hyogo 665, Japan

Address requests for reprints and all correspondence to: Dr. Masaaki Inaba, Second Department of Internal Medicine, Osaka City University Medical School, 1-5-7, Asahi-machi, Abeno-ku, Osaka 545, Japan.

Abstract

The human promyelocytic leukemia cell line, HL-60, differentiated into macrophage/mohocytes in the presence of l,25-dihydroxycholecalciferol [l,25(OH)₂D₃], as assessed by the percentage of morphologically mature cells and their ability to reduce nitroblue tetrazolium. In this study of the mechanism involved, the activities of orriithine decarboxylase and spermidine/spermihe-N¹-acetyltransferase (SAT), the ratelimiting enzymes of polyamine metabolism, as well as the cellular levels of polyamine were measured. ODC activity reached a peak 24 h after the addition of l,25(OH)₂D₃ and then decreased, while SAT activity gradually increased as differentiation commenced. An increase in putrescine and decreases in spermidine and spermine were also observed. Addition of -difluoro-methylornithine, an irreversible inhibitor of ODC, with or without methylglyoxalbis(guanylhydrazone), an inhibitor of S-adenosylmethionihe decarboxylase, caused no effect on l,25(OH)₂D₃-induced cell differentiation, although the cellular levels of putrescine and spermidine decreased markedly. Addition of adifluoromethylornithine markedly suppressed cell proliferation; this effect was reversed by the addition of exogenous putrescine. Addition of exogenous spermidine or spermine to overcome activation of SAT also had no effect on l,25(OH)₂D₃-induced cell differentiation. These results suggest both that polyamine metabolism is not important in l,25(OH)₂D₃-induced differentiation of HL-60 cells, but that it is intimately involved in proliferation of these cells. (Endocrinology 118: 1849–1855, 1986)

Footnotes

*This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan.

Received July 30, 1985.

This article has been cited by other articles:

				I. M. Gavin, D. Glesne, Y. Zhao, C. Kubera, and E. Huberman Spermine Acts as a Negative Regulator of Macrophage Differentiation in Human Myeloid Leukemia Cells Cancer Res., October 15, 2004; 64(20): 7432 - 7438. [Abstract] [Full Text] [PDF]