Effects of 2-Methyl-1,4-naphtoquinone (Menadione) on Cellular Signaling in RBL-2H3 Cells(Analytical Biochemistry)

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Reactive oxygen species (ROS) are produced in various cells and affect many biologic processes. In this study, we examined the effects of 2-methyl-1, 4-naphtoquinone (menadione; vitamine K_3) on signal transduction in mast cells. Several lines of evidence suggest that H_2O_2 affects the antigen-induced responses in mast cells but its mechanism is not clearly understood. Unlike H_2O_2, menadione produces ROS only inside cells. Thus, it is possible to investigate the effects of ROS produced intracellularly. Pretreatment of mast cells (RBL-2H3) with menadione inhibited exocytotic secretion (degranulation) induced by antigen stimulation dose dependently. Menadione also inhibited the intracellular Ca^<2+> increase induced by antigen stimulation. Menadione did not inhibit the Ca^<2+> increase due to Ca^<2+> release from the intracellular calcium store in the absence of extracellular Ca^<2+>, but inhibited the Ca^<2+> influx from the extracellular medium. These results suggest that reactive oxygen generated inside RBL cells by menadione inhibited degranulation by decreasing Ca^<2+> influx through the store operated Ca^<2+> channel on the plasma membrane.
公益社団法人日本薬学会の論文
2006-04-01