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Biochemical J. ,441,2,719-730.pdf2831KbAdobe PDFView/Open
Biochemical J. ,441,2,719-730, supp.pdf1050KbAdobe PDFView/Open
Title :Regulation by mitochondrial superoxide and NADPH oxidase of cellular formation of nitrated cyclic GMP: potential implications for ROS signaling
Authors :Ahmed, Khandaker Ahtesham
Sawa, Tomohiro
Ihara, Hideshi
Kasamatsu, Shingo
Yoshitake, Jun
Rahaman, Md. Mizanur
Okamoto, Tatsuya
Fujii, Shigemoto
Akaike, Takaaki
Issue Date :15-Jan-2012
Citation jtitle :Biochemical Journal
vol. :441
no. :2
start page :719
end page :730
Abstract :8-Nitro-cGMP (8-nitroguanosine 3′,5′-cyclic monophosphate) is a nitrated derivative of cGMP, which can function as a unique electrophilic second messenger involved in regulation of an antioxidant adaptive response in cells. In the present study, we investigated chemical and biochemical regulatory mechanisms involved in 8-nitro-cGMP formation, with particular focus on the roles of ROS (reactive oxygen species). Chemical analyses demonstrated that peroxynitrite-dependent oxidation and myeloperoxidase-dependent oxidation of nitrite in the presence of H 2O 2 were two major pathways for guanine nucleotide nitration. Among the guanine nucleotides examined, GTP was the most sensitive to peroxynitrite-mediated nitration. Immunocytochemical and tandem mass spectrometric analyses revealed that formation of 8-nitro-cGMP in rat C6 glioma cells stimulated with lipopolysaccharide plus pro-inflammatory cytokines depended on production of both superoxide and H 2O 2. Using the mitochondria-targeted chemical probe MitoSOX™ Red, we found that mitochondria-derived superoxide can act as a direct determinant of 8-nitro-cGMP formation. Furthermore, we demonstrated that Nox2 (NADPH oxidase 2)-generated H 2O 2regulated mitochondria-derived superoxide production, which suggests the importance of cross-talk between Nox2-dependent H 2O 2 production and mitochondrial superoxide production. The results of the present study suggest that 8-nitro-cGMP can serve as a unique second messenger thatmay be implicated in regulating ROS signalling in the presence of NO.
URL :http://www.biochemj.org/bj/441/bj4410719.htm
Type Local :雑誌掲載論文
ISSN :02646021
Publisher :Portland Press Ltd.
Rights :© 2012 Portland Press Ltd.
URI :http://hdl.handle.net/2298/25781
Appears in Collections:Journal Article (Medicine)
Please use this identifier to cite or link to this item: http://hdl.handle.net/2298/25781