KMID : 0043320090320111637
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Archives of Pharmacal Research 2009 Volume.32 No. 11 p.1637 ~ p.1642
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Distinct Effects on M2-type Pyruvate Kinase are Involved in the Dimethylsulfoxide-induced Modulation of Cellular Proliferation and Degranulation of Mast Cells
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Kim Kyeong-Man
Koo Na-Youn
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Abstract
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Dimethylsulfoxide (DMSO), a universal solvent, is frequently used to dissolve various classes of chemicals for the evaluation of their biological activities. In one such evaluation, we noticed that DMSO itself caused cellular proliferation and interfered with high affinity IgE receptor (Fc¥åRI)-mediated degranulation of mast cells. DMSO caused cellular proliferation of RBL-2H3 cells by phosphorylating both extracellular-signal regulated kinase (ERK) and M2-type pyruvate kinase (M2PK) through which the enzymatic activity of M2PK was reduced. Allergenic activation of Fc¥åRI caused the tyrosine phosphorylations of signaling components of Fc¥åRI, such as Syk, PLC¥ã1, PLC¥ã2, ERK, and M2PK. In these allergenic activated RBL-2H3 cells, DMSO specifically inhibited Fc¥åRI-mediated tyrosine phosphorylation of M2PK, blocked Fc¥åRI-mediated inhibition of the enzymatic activity of M2PK, and then inhibited Fc¥åRI-mediated degranulation. These results suggest that DMSO causes cellular proliferation and mast cell degranulation through differential modulation of M2PK in resting and allergenic activated cells.
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KEYWORD
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DMSO, Fc¥åRI, M2-type pyruvate kinase, Mast cell degranulation, Cellular proliferation
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