九州大学 研究者情報
著書一覧
西田 基宏(にしだ もとひろ) データ更新日:2023.10.06

教授 /  薬学研究院 臨床薬学部門 生理学分野


著書
1. Motohiro Nishida, Mina Ohba, Michio Nakaya, Hitoshi Kurose, Heterotrimeric g proteins in heart failure, Nova Science Publishers, Inc., 2010.01, 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 diacylglycerolactivated 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 Gαqmediated 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..
2. Motohiro Nishida, Caroline Sunggip, Naoyuki Kitajima, Hitoshi Kurose, Redox regulation of angiotensin receptor signaling in the heart, Nova Science Publishers, Inc., 2012.01, Cardiovascular diseases are leading cause of morbidity and mortality in developed countries. Renin-angiotensin system (RAS) and its effector molecule, angiotensin (Ang) II, play an important role in the pathophysiology of cardiovascular and kidney diseases. Most of the known pathophysiological effects of Ang II are mediated by Ang type 1 receptors (AT1Rs), and up-regulation of AT1Rs is an important event involves in undesired cardiovascular-renal crosstalk. Many lines of evidences have shown that reactive oxygen species (ROS) and reactive nitrogen species (RNS) play significant roles in regulation of AT1R signaling. In our study, we reveal that AT1R-stimulated ROS production mediates activation of mitogen-activated protein kinases (MAPKs), leading to hypertrophic growth of cardiomyocytes and excessive cytokine production by cardiac fibroblasts. These findings indicate that ROS work as a crucial second messenger in Ang II-induced signaling. Endogenous ROS apparently increase AT1R expression level, while RNS down-regulates the expression of AT1R. The differences in the effects of ROS and RNS on AT1R expression can be explained by the local covalent modification of cysteine thiols that are found at active or allosteric sites of effector proteins. This review introduces the recent findings on molecular mechanisms underlying reduction/oxidation (redox)-dependent post-translational regulation of AT1R signaling in the cardiovascular system. These findings will provide a new understanding on the importance of cross talk between Ang II signaling and ROS/RNS in the development of heart failure..
3. 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.
4. 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..
5. Mori Y, Itsukaichi Y, Nishida M & Oka H., Pharmacology of Calcium Channel, Kluwer Academic / Plenum Publishers (New York), Kluwer Academic / Plenum Publishers (New York), 2004.06.

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