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alpha-Tocopherol induces hematopoietic stem/progenitor cell expansion and ERK1/2-mediated differentiation


Tocopherols promote or inhibit growth in different cell types. In the hematopoietic system, the radioprotective property of tocopherols is thought to act through the expansion of primitive hematopoietic cells; however, the hematopoietic progenitors affected and the mechanisms activated by tocopherols remain poorly understood. To better address these questions, mice were treated with a-tocopherol, and its effects were investigated in the bone marrow (BM) microenvironment. a-Tocopherol induced increased proliferation in hematopoietic stem/progenitor cells, leading to BM hyperplasia. In addition, differentiation to the granulocytic/monocytic lineage was enhanced by a-tocopherol treatment. a-Tocopherol treatment resulted in decreased basal phosphorylation of ERK1/2, PKC, and STAT-5 in hematopoietic stem/progenitor cells. In contrast, a-tocopherol enhanced ERK1/2 activation in response to IL-3 stimulation in hematopoietic stem/progenitor cells without altering the expression of IL-3 receptors. Moreover, a-tocopherol-induced differentiation and ERK1/2 activation were abolished in mice pretreated with a MEK inhibitor (PD98059); however, pretreatment with PD98059 did not reduce the a-tocopherol-mediated increase in stem/progenitor cells but instead further enhanced their proliferation. Therefore, alpha-tocopherol induces expansion of stem/progenitor cells by non-identified intracellular pathway and granulocytic/monocytic differentiation through ERK1/2 activation. (AU)

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