Role of polyamines derived from arginine in differentiation and proliferation of human blood cells.
L-Arginine is a precursor of polyamine, nitric oxide (NO), creatine, and agmatine and is essential for the differentiation and proliferation of blood cells, although the precise biological role of L-arginine is unclear. We have recently reported that the depletion of L-arginine in cultured medium prevented both proliferation and differentiation of blood cells (Shima et al., Blood First Edition Paper, October 6, 2005; DOI 10.1182). Since one of metabolic products of L-arginine in the cells is polyamine that associates with cell differentiation and proliferation, the effects of L-arginine on the human K562 cell line and human cord blood-derived CD34 positive cells were investigated by focusing on polyamines such as putrescine, spermidine, and spermine in the present study. When polyamines were added to the culture medium in the absence of L-arginine, the cells did not grow or differentiate well. However, when intracellular polyamines were depleted using ornithine decarboxylase inhibitor, alpha-difluoromethylornithine (DFMO), the proliferation and differentiation of K562 cells to erythrocytes were reduced even in the presence of L-arginine. Moreover, in the presence of DFMO, cell differentiation and proliferation were recovered by the addition of putrescine or spermidine in the presence of L-arginine. Accordingly, it was demonstrated that polyamines are essential for the proliferation and differentiation of the blood cells as the metabolites of L-arginine and the externally added polyamines are also effective by being taken up through polyamine transporter.
Maeda
Tomoji
T
Department of Molecular Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamasaki, Noda, Chiba 278-8510, Japan.
Wakasawa
Takeru
T
Shima
Yoichiro
Y
Tsuboi
Isao
I
Aizawa
Shin
S
Tamai
Ikumi
I
D018952:Antigens, CD34 / Q000378:metabolism; D001120:Arginine / Q000378:metabolism / Q000494:pharmacology*; D015317:Biogenic Polyamines / Q000494:pharmacology*; D001692:Biological Transport; D001773:Blood Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D003470:Culture Media; D000518:Eflornithine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005312:Fetal Blood / Q000166:cytology; D006801:Humans; D020014:K562 Cells; D009955:Ornithine Decarboxylase / Q000378:metabolism
D018952:Antigens, CD34; D015317:Biogenic Polyamines; D003470:Culture Media; D004791:Enzyme Inhibitors; D001120:Arginine; D009955:Ornithine Decarboxylase; D000518:Eflornithine