title: Molecular hydrogen suppresses FcepsilonRI-mediated signal transduction and prevents degranulation of mast cells.
abstract: Molecular hydrogen ameliorates oxidative stress-associated diseases in animal models. We found that oral intake of hydrogen-rich water abolishes an immediate-type allergic reaction in mice. Using rat RBL-2H3 mast cells, we demonstrated that hydrogen attenuates phosphorylation of the FcepsilonRI-associated Lyn and its downstream signal transduction, which subsequently inhibits the NADPH oxidase activity and reduces the generation of hydrogen peroxide. We also found that inhibition of NADPH oxidase attenuates phosphorylation of Lyn in mast cells, indicating the presence of a feed-forward loop that potentiates the allergic responses. Hydrogen accordingly inhibits all tested signaling molecule(s) in the loop. Hydrogen effects have been solely ascribed to exclusive removal of hydroxyl radical. In the immediate-type allergic reaction, hydrogen exerts its beneficial effect not by its radical scavenging activity but by modulating a specific signaling pathway. Effects of hydrogen in other diseases are possibly mediated by modulation of yet unidentified signaling pathways. Our studies also suggest that hydrogen is a gaseous signaling molecule like nitric oxide.
authors.affiliation: Department of Longevity and Aging Research, Gifu International Institute of Biotechnology, 1-1 Naka-fudogaoka, Kakamigahara, Gifu, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Itoh
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Fujita
authors.forename: Mikako
authors.initials: M
authors.lastname: Ito
authors.forename: Akio
authors.initials: A
authors.lastname: Masuda
authors.forename: Kinji
authors.initials: K
authors.lastname: Ohno
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Ichihara
authors.forename: Toshio
authors.initials: T
authors.lastname: Kojima
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Nozawa
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ito
mesh_terms: D000818:Animals; D015550:Cell Degranulation / Q000187:drug effects*; D045744:Cell Line, Tumor; D006859:Hydrogen / Q000494:pharmacology*; D008407:Mast Cells / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR; D019255:NADPH Oxidases / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017455:Receptors, IgE / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D017455:Receptors, IgE; D006859:Hydrogen; D019255:NADPH Oxidases; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases