Kyushu University Academic Staff Educational and Research Activities Database
List of Reports
Motohiro Nishida Last modified date:2020.01.10

Professor / Department of Translational Pharmaceutical Sciences / Department of Pharmaceutical Health Care and Sciences / Faculty of Pharmaceutical Sciences

1. Caroline Sunggip, Naoyuki Kitajima, Motohiro Nishida, Redox control of cardiovascular homeostasis by angiotensin II, Current Pharmaceutical Design, 10.2174/1381612811319170008, 2013, Covalent modification of sulfur-containing amino acids in proteins by reactive oxygen species (ROS) has been attracting attention as a major post-translational modification regulating intracellular signal transduction pathways. Angiotensin II (Ang II), a major physiologically active substrate in renin-angiotensin (RAS) system, plays a central role in the pathophysiology of cardiovascular systems. Many evidences show that Ang II activates several signaling pathways via an oxidative modification of proteins by Ang II-induced ROS. Ang II induced ROS production is predominantly regulated by three enzymes: NADPH oxidase, mitochondrial respiratory complex, and nitric oxide synthase (NOS), and each enzyme-generating ROS are found to activate appropriate signaling pathways via selective oxidation of specific proteins. These reactions are negatively regulated by ROS-scavenging enzymes or disulfide bridge reducing enzymes, and functional disorders of these enzymes are found to cause cardiovascular dysfunctions. Thus, the spatial and temporal regulation of oxidative modification of signaling proteins by ROS is essential to maintain cardiovascular homeostasis by Ang II. This review brings in the new aspect in understanding ROS-mediated regulation of cardiovascular homeostasis by Ang II, and provides the possible mechanisms underlying metamorphosis of cardiovascular homeostasis by ROS..
2. Tomohiro Sawa, Hideshi Ihara, Tomoaki Ida, Shigemoto Fujii, Motohiro Nishida, Takaaki Akaike, Formation, signaling functions, and metabolisms of nitrated cyclic nucleotide, Nitric Oxide - Biology and Chemistry, 10.1016/j.niox.2013.04.004, 2013.01, 8-Nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP) is a unique derivative of guanosine 3',5'- cyclic monophosphate (cGMP) formed in mammalian and plant cells in response to production of nitric oxide and reactive oxygen species. 8-Nitro-cGMP possesses signaling activity inherited from parental cGMP, including induction of vasorelaxation through activation of cGMP-dependent protein kinase. On the other hand, 8-nitro-cGMP mediates cellular signaling that is not observed for native cGMP, e.g., it behaves as an electrophile and reacts with protein sulfhydryls, which results in cGMP adduction to protein sulfhydryls (protein S-guanylation). Several proteins have been identified as targets for endogenous protein S-guanylation, including Kelch-like ECH-associated protein 1 (Keap1), H-Ras, and mitochondrial heat shock proteins. 8-Nitro-cGMP signaling via protein S-guanylation of those proteins may have evolved to convey adaptive cellular stress responses. 8-Nitro-cGMP may not undergo conventional cGMP metabolism because of its resistance to phosphodiesterases. Hydrogen sulfide has recently been identified as a potent regulator for metabolisms of electrophiles including 8-nitro-cGMP, through sulfhydration of electrophiles, e.g., leading to the formation of 8-SH-cGMP. Better understanding of the molecular basis for the formation, signaling functions, and metabolisms of 8-nitro-cGMP would be useful for the development of new diagnostic approaches and treatment of diseases related to oxidative stress and redox metabolisms..
3. Naoyuki Kitajima, Motohiro Nishida, Chemical biology of hydrogen sulfide, Folia Pharmacologica Japonica, 10.1254/fpj.141.350, 2013.01.
4. Takaaki Akaike, Motohiro Nishida, Shigemoto Fujii, Regulation of redox signalling by an electrophilic cyclic nucleotide, Journal of Biochemistry, 10.1093/jb/mvs145, 2013.02, Reactive oxygen species (ROS) have been believed to be toxic substances that induce nonspecific damage in various biological molecules. ROS toxicology is now developing an emerging concept for physiological functions of ROS in the regulation of cell signal transductions. ROS signalling functions and their mechanisms are precisely regulated by several endogenous moderate electrophiles that are themselves generated from ROS during diverse physiological and pathophysiological cellular responses. The chemical biology of electrophiles is an emerging scientific area involving molecular mechanisms that conduct ROS cell signals through receptors to effector molecules at molecular, cellular and organism levels. The formation, signalling and metabolism of 8-nitroguanosine 3′,5′-cyclic monophosphate (8-nitro-cGMP) in cells are probably precisely regulated, and nonselective ROS reactions can be converted into stable, well-controlled electrophilic signal transduction via 8-nitro-cGMP. Modern redox biology is today advancing its frontier of basic research and clinical medicine, including infection, cancer biology, metabolic syndromes, ageing and even stem cell research. As one aspect of this advance, the 8-nitro-cGMP-mediated signalling that may be integrated into cells as a major redox signalling pathway may be a potential target in drug development and may lead to discovery of new therapeutic agents for various diseases..
5. Motohiro Nishida, Masaaki Sumita, Naoyuki Kitajima, [Function and role of transient receptor potential channels]., Clinical calcium, 2013.04, Transient receptor potential (TRP) proteins are components of Ca(2 +) -permeable non-selective cation channels activated by physical and chemical stimulus except for membrane depolarization. The pathophysiological role of TRP channels is documented in heart failure. Especially, canonical TRP subfamily C (TRPC) channels activated by neurohumoral factors have been implicated in the structural remodeling of the heart. TRPC proteins act not only as components of receptor-activated cation channels, but also as protein scaffold to form protein complex with intracellular signaling proteins, leading to amplification of receptor signaling. Recently, selective inhibitors of TRPC channels have been continuously identified, anticipating the possibility of drug discovery targeting TRPC channels for the treatment of heart failure..
6. Nishida M, Roles of heterotrimetric GTP-binding proteins in the progression of heart failure., J. Pharmacol. Sci., 2011.06.
7. Nishida M, Kitajima N, Saiki S, Nakaya M & Kurose H, Regulation of angiotensin II receptor signaling by cysteine modification of NF-kB., Nitric Oxide, 2011.08.
8. Nakaya M, Ohba M, Nishida M & Kurose H., Determining the activation of Rho as an index of coupling to G12/13., Methods in Molecular Biology, 2010.12.
9. Nishida M, Kitajima N, Saiki S, Nakaya M & Kurose H., Regulation of angiotensin II receptor signaling by cysteine modification of NF-kB., Nitric Oxide, in press..
10. Nishida M. , Heterotrimetric G protein signaling in Heart Failure. , J. Pharmacol. Sci., in press..
11. Nishida M, Kurose H, Roles of TRP channels in the development of cardiac hypertrophy., Naunyn Schmiedebergs Arch Pharmacol. , Vol.378,395-406, 2008.07.
12. Yamamoto S, Wajima T, Hara Y, Nishida M & Mori Y., Transient receptor potential channels in Alzheimer's disease., Biochim Biophys Acta., Vol.1772, 958-967, 2007.08.
13. Nishida M, Hara Y, Yoshida T, Inoue R & Mori Y., TRP channels: formation of signal complex and regulation of cellular functions, Microcirculation, 13, 535-550, 2006.09.
14. Inoue R, Jensen LJ, Shi J, Morita H, Nishida M, Honda A & Ito Y, Transient receptor potential (TRP) channels in cardiovascular function and disease, Circ. Res, 99, 119-131, 2006.06.
15. Mori Y, Itsukaichi Y, Nishida M & Oka H, Ca2+ channel mutations and associated diseases., Kluwer Academic / Plenum Publishers (New York), Pharmacology of Calcium Channel,Edited by McDonough SI. 303-330 (2004)., 2004.06.
16. Mori Y, Nishida M, Shimizu S, Ishii M, Yoshinaga T, Ino M, Sawada K & Niidome T, Mice lacking the a1B subunit (CaV 2.2) reveals a predominant role of N-type Ca2+ channels in the sympathetic regulation of circulatory system., Trends in Cardiovascular Medicine, 12, 270-275, 2002.12.