Distinct effects on M2-type pyruvate kinase are involved in the dimethylsulfoxide-induced modulation of cellular proliferation and degranulation of mast cells.
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 (FcepsilonRI)-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 FcepsilonRI caused the tyrosine phosphorylations of signaling components of FcepsilonRI, such as Syk, PLCgamma1, PLCgamma2, ERK, and M2PK. In these allergenic activated RBL-2H3 cells, DMSO specifically inhibited FcepsilonRI-mediated tyrosine phosphorylation of M2PK, blocked FcepsilonRI-mediated inhibition of the enzymatic activity of M2PK, and then inhibited FcepsilonRI-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.
Koo
Nayoun
N
Pharmacology Laboratory, College of Pharmacy, Chonnam National University, Kwang-Ju, Korea.
Kim
Kyeong-Man
KM
D000818:Animals; D015550:Cell Degranulation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011770:Pyruvate Kinase / Q000378:metabolism*; D051381:Rats; D017455:Receptors, IgE / Q000378:metabolism; D012997:Solvents / Q000494:pharmacology*
D017455:Receptors, IgE; D012997:Solvents; D011770:Pyruvate Kinase; D048049:Extracellular Signal-Regulated MAP Kinases; D004121:Dimethyl Sulfoxide