Cell signaling mediated by nitrated cyclic guanine nucleotide
| العنوان: | Cell signaling mediated by nitrated cyclic guanine nucleotide |
|---|---|
| المؤلفون: | Tomohiro Sawa, Takaaki Akaike, Shigemoto Fujii, Hideshi Ihara |
| المصدر: | Nitric oxide : biology and chemistry. 23(3) |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | chemistry.chemical_classification, Cancer Research, Cell signaling, Physiology, Chemistry, Clinical Biochemistry, 8-Nitro-cGMP, Nitric Oxide, Biochemistry, KEAP1, S-Guanylation, chemistry.chemical_compound, Cyclic nucleotide, Nitrated cyclic nucleotide, Second messenger system, Humans, Nucleotide, Signal transduction, Heme, Cyclic GMP, Cysteine, Signal Transduction |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| تدمد: | 1089-8611 1089-8603 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e484a5c7d8f9d0aaf786a6c23946556e https://pubmed.ncbi.nlm.nih.gov/20601047 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e484a5c7d8f9d0aaf786a6c23946556e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10898611 10898603 |
|---|