Redox signaling regulated by an electrophilic cyclic nucleotide and reactive cysteine persulfides.
Reactive oxygen (oxidant) and free radical species are known to cause nonspecific damage of various biological molecules. The oxidant toxicology is developing an emerging concept of the physiological functions of reactive oxygen species in cell signaling regulation. Redox signaling is precisely modulated by endogenous electrophilic substances that are generated from reactive oxygen species during cellular oxidative stress responses. Among diverse electrophilic molecular species that are endogenously generated, 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP) is a unique second messenger whose formation, signaling, and metabolism in cells was recently clarified. Most important, our current studies revealed that reactive cysteine persulfides that are formed abundantly in cells are critically involved in the metabolism of 8-nitro-cGMP. Modern redox biology involves frontiers of cell research and stem cell research; medical and clinical investigations of infections, cancer, metabolic syndrome, aging, and neurodegenerative diseases; and other fields. 8-Nitro-cGMP-mediated signaling and metabolism in cells may therefore be potential targets for drug development, which may lead to discovery of new therapeutic agents for many diseases.
Department of Environmental Health Sciences and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
Shigemoto
S
Fujii
Department of Microbiology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
Tomohiro
T
Sawa
Division of Cardiocirculatory Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), National Institutes of Natural Sciences, Aichi 444-8787, Japan; Department of Translational Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan; PRESTO, Japan Science and Technology Agency (JST), Kawaguchi, Saitama 332-0012, Japan.
Motohiro
M
Nishida
Department of Biological Science, Graduate School of Science, Osaka Prefecture University, Osaka 599-8531, Japan.
Hideshi
H
Ihara
Department of Environmental Health Sciences and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
Tomoaki
T
Ida
Department of Gene Expression Regulation, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan.
Hozumi
H
Motohashi
Department of Environmental Health Sciences and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan. Electronic address: takaike@med.tohoku.ac.jp.
Takaaki
T
Akaike
D000818:Animals; D003545:Cysteine / Q000378:metabolism*; D006801:Humans; D009712:Nucleotides, Cyclic / Q000378:metabolism*; D010084:Oxidation-Reduction; D015290:Second Messenger Systems; D015398:Signal Transduction; D013440:Sulfides / Q000378:metabolism*
D009712:Nucleotides, Cyclic; D013440:Sulfides; C051552:persulfides; D003545:Cysteine
8-Nitro-cGMP; Electrophilic signaling; NO; Redox signaling