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Cell signaling mediated by nitrated cyclic guanine nucleotide 赤池, 孝章 藤井, 重元 澤, 智裕 Ihara, Hideshi 居原, 秀 イハラ, ヒデシ Ihara 居原 イハラ Hideshi 秀 ヒデシ 赤池, 孝章 アカイケ, タカアキ Akaike, Takaaki 赤池 アカイケ Akaike 孝章 タカアキ Takaaki 藤井, 重元 フジイ, シゲモト Fujii, Shigemoto 藤井 フジイ Fujii 重元 シゲモト Shigemoto 澤, 智裕 サワ, トモヒロ Sawa, Tomohiro 澤 サワ Sawa 智裕 トモヒロ Tomohiro Ihara, Hideshi 居原, 秀 イハラ, ヒデシ Ihara 居原 イハラ Hideshi 秀 ヒデシ © 2010 Elsevier Inc. 465 Cell signaling Nitric oxide Nitrated cyclic nucleotide 8-Nitro-cGMP S-Guanylation application/pdf 論文(Article) We recently clarified the physiological formation of 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP) and its critical roles in nitric oxide (NO) signal transductions. This discovery of 8-nitro-cGMP is the first demonstration of a nitrated cyclic nucleotide functioning as a new second messenger in mammals since the identification of cGMP more than 40. years ago. By means of chemical analyses, e.g., liquid chromatography-tandem mass spectrometry, we unequivocally identified 8-nitro-cGMP formation, which depended on NO production, in several types of cultured cells, including macrophages and glial cells. Most important, we previously showed that 8-nitro-cGMP as an electrophile reacted with particular sulfhydryls of proteins to generate a unique post-translational modification that we called protein S-guanylation. In fact, certain specific intracellular proteins, such as the redox-sensor protein Keap1, readily underwent S-guanylation induced by 8-nitro-cGMP. 8-Nitro-cGMP activated the Nrf2 signaling pathway by triggering dissociation of Keap1, via S-guanylation of its highly nucleophilic cysteine sulfhydryls. We also determined that S-guanylation of Keap1 was involved in cytoprotective actions of NO and 8-nitro-cGMP by inducing oxidative stress response genes such as heme oxygenase-1. Such unique chemical properties of 8-nitro-cGMP shed light on new areas of NO and cGMP signal transduction. Protein S-guanylation induced by 8-nitro-cGMP may thus have important implications in NO-related physiology and pathology, pharmaceutical chemistry, and development of therapeutics for many diseases. http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WNT-50CV846-1&_user=4545557&_coverDate=11%2F01%2F2010&_rdoc=1&_fmt=high&_orig=search&_origin=search&_sort=d&_docanchor=&view=c&_acct=C000008298&_version=1&_urlVersion=0&_userid=4545557&md5=9e7e99db7729f8c21d50cffe81f352c2&searchtype=a Elsevier 2010-11 eng journal article AM http://hdl.handle.net/2298/17931 https://kumadai.repo.nii.ac.jp/records/24525 10.1016/j.niox.2010.06.006 10898603 Nitric Oxide - Biology and Chemistry 23 3 166 174 https://kumadai.repo.nii.ac.jp/record/24525/files/NOBC23_3_166-174.pdf application/pdf 668.2 kB 2020-03-02