Publications (1)0 Total impact
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Tomohiro Sawa,
Mohammad Hasan Zaki,
Tatsuya Okamoto,
Teruo Akuta,
Yoshiko Tokutomi,
Shokei Kim-Mitsuyama,
Hideshi Ihara,
Akira Kobayashi,
Masayuki Yamamoto,
Shigemoto Fujii, [......],
シゲモト フジイ,
ヒデカズ アリモト,
タカアキ アカイケ,
智裕 澤,
竜哉 岡本,
照夫 芥, 芳子 徳冨,
勝慶 光山,
重元 藤井,
孝章 赤池
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ABSTRACT: The signaling pathway of nitric oxide (NO) depends mainly on guanosine 3′,5′-cyclic monophosphate (cGMP, 1). Here we report the formation and chemical biology of a nitrated derivative of cGMP, 8-nitroguanosine 3′,5′-cyclic monophosphate (8-nitro-cGMP, 2), in NO-mediated signal transduction. Immunocytochemistry demonstrated marked 8-nitro-cGMP production in various cultured cells in an NO-dependent manner. This finding was confirmed by HPLC plus electrochemical detection and tandem mass spectrometry. 8-Nitro-cGMP activated cGMP-dependent protein kinase and showed unique redox-active properties independent of cGMP activity. Formation of protein Cys-cGMP adducts by 8-nitro-cGMP was identified as a new post-translational modification, which we call protein S-guanylation. 8-Nitro-cGMP seems to regulate the redox-sensor signaling protein Keap1, via S-guanylation of the highly nucleophilic cysteine sulfhydryls of Keap1. This study reveals 8-nitro-cGMP to be a second messenger of NO and sheds light on new areas of the physiology and chemical biology of signal transduction by NO.
15524450.
