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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

        Nayoun Koo,Kyeong-Man Kim 대한약학회 2009 Archives of Pharmacal Research Vol.32 No.11

        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 (FcεRI)-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 FcεRI caused the tyrosine phosphorylations of signaling components of FcεRI, such as Syk, PLCγ1, PLCγ2, ERK, and M2PK. In these allergenic activated RBL-2H3 cells, DMSO specifically inhibited FcεRI-mediated tyrosine phosphorylation of M2PK, blocked FcεRI-mediated inhibition of the enzymatic activity of M2PK, and then inhibited FcεRI-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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