Kyushu University Academic Staff Educational and Research Activities Database
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Motohiro Nishida Last modified date:2022.06.29



Graduate School
Undergraduate School


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Homepage
https://kyushu-u.pure.elsevier.com/en/persons/motohiro-nishida
 Reseacher Profiling Tool Kyushu University Pure
http://soyaku.phar.kyushu-u.ac.jp/
Phone
092-642-6556
Fax
092-642-6556
Academic Degree
Ph.D.
Country of degree conferring institution (Overseas)
No
Field of Specialization
Pharmacology, Physiology
ORCID(Open Researcher and Contributor ID)
0000-0002-2587-5458
Total Priod of education and research career in the foreign country
00years00months
Outline Activities
Research:
Study on the intracellular signaling pathways regulating adaptation or maladaptation of the heart against physical stresses
Study on the regulation of cardiac redox homeostasis by reactive sulfur species
Study on the pathophysiological roles of receptor-activated TRPC channels in the heart
Drug discovery and evolution focusing on mitochondrial quality control

Education:
Pharmacology, Drug Disovery and Evolution

Social activities:
presentation in scientific meeting, lecturer on demand (high school), etc.
Research
Research Interests
  • Green-Pharma Research focusing on the pathology-specific protein-protein interactions
    keyword : intractable disease, muscle atrophy, protein-protein interaction (PPI), drug development and repositioning
    2015.09.
  • Role of receptor-activated TRP calcium channels in cardiocirculatory homeostasis
    keyword : cardiocirculatory homeostasis, TRPC channel, autonomic nervous system
    2018.04.
  • Physiological role of supersulfides
    keyword : Supersulfides, muscles, mitochondria, repair and regeneration
    2019.04.
Current and Past Project
  • Study on the development of quantitative imaging of supersulfides and elucidation of their physiological roles
Academic Activities
Books
1. Nishida M, Sunggip C, Kitajima N & Kurose H, Angiotensin: New Research, Redox regulation of angiotensin receptor signaling in the heart., NOVA Publishers (New York), 2012.03.
2. Nishida M, Ohba M, Nakaya M & Kurose H., Heart Failure: Symptoms, Causes and Treatment Options, NOVA Publishers (New York), 2011.03, Structural remodeling of the heart, including myocardial hypertrophy and fibrosis, is a key determinant for the clinical outcome of heart failure. A variety of evidence indicates the importance of neurohumoral factors, such as endothelin-1, angiotensin II, and norepinephrine for the initial phase of the development of cardiac remodeling. These agonists stimulate seven transmembrane spanning receptors that are coupled to heterotrimeric GTP-binding proteins (G proteins) of the Gi, Gq and G12 subfamilies. The pathophysiological roles of each G protein-mediated signaling have been revealed by studies using transgenic and knockout mice. Using specific pharmacological tools to assess the involvement of G protein signaling pathways, we have found that diacylglycerol-activated transient receptor potential canonical (TRPC) channels (TRPC3 and TRPC6), one of the downstream effectors regulated by Gαq, work as a key mediator in the development of cardiac hypertrophy. In contrast, we also revealed that activation of Gα12 family proteins in cardiomyocytes mediates pressure overload-induced cardiac fibrosis. Stimulation of purinergic P2Y6 receptors by extracellular nucleotides released by mechanical stretch is a trigger of Gα12-mediated fibrotic responses of the heart. Although cardiac fibrosis is believed to accompany with Gαq-mediated pathological hypertrophy that eventually results in heart failure, our results clearly show that cardiac fibrosis and hypertrophy are independent processes. These findings will provide a new insight into the molecular mechanisms underlying pathogenesis of heart failure..
Reports
1. 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.
2. Nishida M, Roles of heterotrimetric GTP-binding proteins in the progression of heart failure., J. Pharmacol. Sci., 2011.06.
3. Nishida M, Hara Y, Yoshida T, Inoue R & Mori Y., TRP channels: formation of signal complex and regulation of cellular functions, 2006.09.
4. 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., 2002.12.
5. Nishida M. , Heterotrimetric G protein signaling in Heart Failure. , J. Pharmacol. Sci., in press..
Papers
1. 西田 基宏, The purinergic P2Y6 receptor heterodimerizes with the angiotensin AT1 receptor to promote angiotensin II-induced hypertension, Science Signaling, doi: 10.1126/scisignal.aac9187., Vol. 9, Issue 411, ra7, 2016.01, The angiotensin (Ang) type 1 receptor (AT1R) promotes functional and structural integrity of the arterial wall to contribute to vascular homeostasis, but this receptor also promotes hypertension. In our investigation of how Ang II signals are converted by the AT1R from physiological to pathological outputs, we found that the purinergic P2Y6 receptor (P2Y6R), an inflammation-inducible G protein (heterotrimeric guanine nucleotide–binding protein)–coupled receptor (GPCR), promoted Ang II–induced hypertension in mice. In mice, deletion of P2Y6R attenuated Ang II–induced increase in blood pressure, vascular remodeling, oxidative stress, and endothelial dysfunction. AT1R and P2Y6R formed stable heterodimers, which enhanced G protein–dependent vascular hypertrophy but reduced β-arrestin–dependent AT1R internalization. Pharmacological disruption of AT1R-P2Y6R heterodimers by the P2Y6R antagonist MRS2578 suppressed Ang II–induced hypertension in mice. Furthermore, P2Y6R abundance increased with age in vascular smooth muscle cells. The increased abundance of P2Y6R converted AT1R-stimulated signaling in vascular smooth muscle cells from β-arrestin–dependent proliferation to G protein–dependent hypertrophy. These results suggest that increased formation of AT1R-P2Y6R heterodimers with age may increase the likelihood of hypertension induced by Ang II..
2. Nishida M, Ogushi M, Suda R, Toyotaka M, Saiki S, Kitajima N, Nakaya M, Kim K-M, Ide T, Sato Y, Inoue K and Kurose H, Heterologous down-regulation of angiotensin type1 receptors by purinergic P2Y2 receptor stimulation through S-nitrosylation of NF-kB., Proc. Natl. Acad. Sci. USA., 10.1073/pnas.1017640108, 108, 6662-6667, 2011.04.
3. Kinoshita H, Kuwahara K, Nishida M, Jiang Z, Rong X, Kiyonaka S, Kuwabara Y, Kurose H, Inoue R, Mori Y, Li Y, Nakagawa Y, Usami S, Fujiwara M, Yamada Y, Minami T, Ueshima K and Nakao K., Inhibition of TRPC6 channel activity contributes to the anti-hypertrophic effects of natriuretic peptides-guanylyl cyclase-A signaling in the heart., Circulation Research, in press, 2010.06.
4. Nishida M, Sakamoto K, Urushidani T & Nagao T, Treatment with l-cis diltiazem before reperfusion reduces infarct size in the ischemic rabbit heart in vivo., The Journal of Pharmaceutical Sciences, 80, 319-325, 1999.07.
5. Nishida M, Nagao T & Kurose H, Activation of Rac1 increases c-Jun NH2-terminal kinase activity and DNA fragmentation in a calcium-dependent manner in rat myoblast cell line H9c2., Biochemical and Biophysical Research Communication, 262, 350-354, 1999.08.
6. Nishida M, Urushidani T, Sakamoto K & Nagao T, l-cis Diltiazem attenuates intracellular Ca2+ overload by metabolic inhibition in guinea pig myocytes., The European Journal of Pharmacology, 385, 225-230, 1999.12.
7. Nishida M, Maruyama Y, Tanaka R, Kontani K, Nagao T, & Kurose H, Gai and Gao are target proteins of reactive oxygen species., Nature, 408, 492-495, 2000.12.
Presentations
1. 西田 基宏, Regulation of cardiac oxygen remodeling via electrophilic modification of Drp1, The 89th Annual Meeting of the Japanese Biochemical Society, 2017.09.
2. 西田 基宏, New strategies for drug development of heart failure, Medical Research Seminar in Malaysia Sabah University, 2017.01.
3. 西田 基宏, Myocardial early senescence mediated by mitochondria-cytoskeleton interaction, The 39th Annual Meeting of the Molecular Biology Society of Japan, 2016.12, Myocardial early senescence mediated by mitochondria-cytoskeleton interaction.
4. 西田 基宏, TRPC channels in cardiovascular stress resilience, International and Interdisciplinary Symposium 2016 “Towards a New Era of Cardiovascular Research, 2016.07.
5. 西田 基宏, Redox regulation of G proteins in cardiac remodeling, The 9th International Conference on the Biology, Chemistry, and Therapeutic Applications of Nitric Oxide, 2016.05.
Membership in Academic Society
  • Physiological Society of Japan
  • Society for Free Radical Research Japan
  • International Society for Heart Research
Awards
  • Award
  • Hydrogen sulfide suppresses H-Ras-mediated cardiac senescence after myocardial infarction via electrophilic sulfhydration
  • Roles of Heterotrimeric GTP-binding Proteins in the Progression of Heart Failure
  • ATP decreases angiotensin type 1 receptor expression through S-nitrosylation of nuclear factor κB
Educational
Educational Activities
Pharmacology I
Practical Training of Research Technique
Presentation Practice I, II in Clinical Pharmaceutics
Advanced Research in Clinical Pharmaceutics