Expression of organic cation transporter OCTN1 in hematopoietic cells during erythroid differentiation

Kobayashi, Daisuke; Aizawa, Shin; Maeda, Tomoji; Tsuboi, Isao; Yabuuchi, Hidetake; Nezu, Jun-ichi; Tsuji, Akira; Tamai, Ikumi

doi:10.1016/j.exphem.2004.08.009

Cited by 35 publications

(27 citation statements)

References 16 publications

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“…We have recently reported that the expression of organic cation/carnitine transporter OCTN1 is associated to the differentiation of the blood cells to erythrocytes. 27) As has been shown in the present study, the substrates of the membrane transporters should determine the differentiation and/or proliferation of cells. Since the substrates of transporters are usually low molecular weight compounds, controlling the constituents of the cell culture medium based on the information of the expressed transporter molecules should be useful to manipulate selective growth of the cells.…”

Section: Discussionmentioning

confidence: 99%

Role of Polyamines Derived from Arginine in Differentiation and Proliferation of Human Blood Cells

Maeda

Wakasawa

Shima

et al. 2006

Biological & Pharmaceutical Bulletin

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The murine cationic amino acid transporter 1 (mCAT1) protein mediates membrane transports of L-arginine, L-lysine, L-histidine, and L-ornithine. The importance of mCAT1-mediated transport was underscored by the phenotype of mCAT1 gene-knockout mice, which exhibit anemia. 1) In addition, we reported that L-arginine that is a substrate of CAT1 is essential for the differentiation to erythrocyte by in vitro cell culture study.2) It has been also observed that L-arginine deficiency affects maturation of early B cells in the bone marrow, but not development of the T cells in the thymus. 3)However, the detailed biological role of the L-arginine in proliferation and differentiation of blood cells and K562 cells that are human leukemia cell line is not clear. L-Arginine is the precursor of polyamines, nitric oxide (NO), and agmatine that are associated with cell proliferation and differentiation.4) While NO can induce an apoptosis of megakaryocytes and a formation of platelet, 5,6) it was reported that NO inhibited differentiation of K562 cells. 7) L-Ornithine is produced by arginase and further metabolized into polyamines such as putrescine, spermidine and spermine, which regulate the cell cycle.8) Moreover, there is some evidence that agmatine acts as an antiproliferative molecule through induction of the protein antizyme.9) Antizyme inhibits ornithine decarboxylase (ODC), hence polyamine biosynthesis. At the same time, antizyme suppresses polyamine uptake. Based on these reports, it was considered that polyamines might be metabolic products of L-arginine that can facilitate differentiation of hematopoietic precursors to erythrocytes.Polyamines (putrescine, spermidine and spermine) play a crucial role in regulating gene expression, signal transduction, ion channel function, DNA and protein synthesis, as well as cell proliferation and differentiation.10) The intracellular polyamine concentration in human erythrocytes is reported to be relatively high; putrescine 0.6 mM (males), and 0.9 mM (females); spermidine 18 and 24 mM; spermine 19 and 15 mM. 11) Polyamines are also scavengers of reactive oxygen species, thereby protecting DNA, protein, and lipids from oxidative damage.12) Available evidence shows that polyamines are key regulators of angiogenesis, early mammalian embryogenesis, placental trophoblast growth, and embryonic development.13) The cellular polyamines are thought to be supplied through de novo synthesis from L-arginine and transport, while the mammalian polyamine transporter gene has not been identified, 14,15) unlike bacterial and/or fungal polyamine transporter. 10,16) De novo polyamine synthesis is governed in part by the activity of ornithine decarboxylase (ODC), which catalyzes the conversion of the amino acid, L-ornithine to the diamine and putrescine. When the ODC activity was inhibited by alpha-difluoromethylornithine (DFMO) in K562 cells, proliferation of K562 cells was inhibited through abolishment of intracellular polyamines.17) It was also reported that spermine induced hemoglobin production i...

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Section: Discussionmentioning

confidence: 99%

Role of Polyamines Derived from Arginine in Differentiation and Proliferation of Human Blood Cells

Maeda

Wakasawa

Shima

et al. 2006

Biological & Pharmaceutical Bulletin

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“…[9][10][11] Furthermore, we previously suggested that OCTN1 is expressed preferentially in erythroid cells. 7,8) Accordingly, OCTN1 is considered to be a physiologically important transporter in several cells such as blood cells, whereas its physiological roles remain to be clarified. As substrates of OCTN1, organic cations such as TEA and carnitine were demonstrated considering from the closely related transporter family members such as organic cation transporters OCTs and carnitine transporter OCTN2.…”

Section: Discussionmentioning

confidence: 99%

“…[3][4][5] Based on expression of OCTN1 in kidney, we previously found that OCTN1 was localized on the apical membrane of renal proximal tubular epithelial cells and suggested that it is involved in the tubular secretion of cationic compounds. 6) Furthermore, based on preferential expression of OCTN1 in erythroid cells, 7) we also suggested that its physiological role is closely associated with differentiation and/or growth of blood cells, 8) while its physiological substrates have not been clearly identified yet.…”

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confidence: 99%

Functional Characterization of Ergothioneine Transport by Rat Organic Cation/Carnitine Transporter Octn1 (slc22a4)

Nakamura

Yoshida

Yabuuchi³

et al. 2008

Biological & Pharmaceutical Bulletin

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“…The spleen cells were then washed twice with α-MEM and mononuclear cells of the BM were obtained. Lin (-) spleen cells were collected using the above-mentioned antibodies and immunomagnetic beads as described previously (15). Briefly, Mac-1-, TER119-, Gr-1-, Thy1.…”

Section: Isolation Of Lineage-negative Spleen Cells [Lin (-) Spleen Cmentioning

confidence: 99%

In Vitro Effect of Neopterin on Splenic Mast Cell Development in Senescence Accelerated Mice (SAM)

Harada

Tsuboi

Yuda³

et al. 2007

Pteridines

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Neopterin is produced by monocytes and is a useful biomarker of inflammatory responses. We found that neopterin enhances granulopoiesis, but suppresses B-lymphopoiesis triggered by the positive-and negative regulations of cytokines produced by stromal cells in mice. Furthermore, neopterin suppressed the colony formation of mast cell progenitor (CFU-mast) from bone marrow cells in in vitro culture system. In this study, neopterin was also found to regulate the proliferation and differentiation of splenic CFU-mast in vitro as observed in that from bone marrow, which was confirmed in the mouse model of senescent stromal-cell impairment (SCI). In non-SCI mice (=less senescent stage of SCI mice), neopterin also decreased the number of colonies of interleukin-3 (IL-3)-dependent mast-cell progenitor cells (CFU-mast) from unfractionated spleen cells, but not that from the lineage-negative (fractionated) spleen cell population without stromal cells in a semisolid in vitro culture system. In contrast, in a case of SCI mice, the treatment with neopterin did not decrease the number of colonies of IL-3-dependent mast-cell progenitor cells (CFU-mast) from unfractionated spleen cells. These results suggest that, firstly, neopterin decrease the number of colonies of IL-3-dependent CFU-mast by stimulating splenic stromal cells, and secondly, such neopterin function becomes declined during senescence because of an impaired stromalcell function.

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Expression of organic cation transporter OCTN1 in hematopoietic cells during erythroid differentiation

Cited by 35 publications

References 16 publications

Role of Polyamines Derived from Arginine in Differentiation and Proliferation of Human Blood Cells

Role of Polyamines Derived from Arginine in Differentiation and Proliferation of Human Blood Cells

Functional Characterization of Ergothioneine Transport by Rat Organic Cation/Carnitine Transporter Octn1 (slc22a4)

In Vitro Effect of Neopterin on Splenic Mast Cell Development in Senescence Accelerated Mice (SAM)

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