研究等業績 - 原著論文 - 岡本 洋介
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Igarashi W.
International Journal of Molecular Sciences ( International Journal of Molecular Sciences ) 24 ( 13 ) 10501 - 10501 2023年07月
研究論文（学術雑誌）
Atrial fibrillation (AF) is the most frequent persistent arrhythmia. Many genes have been reported as a genetic background for AF. However, most transcriptome analyses of AF are limited to the atrial samples and have not been evaluated by multiple cardiac regions. In this study, we analyzed the expression levels of protein-coding and long noncoding RNAs (lncRNAs) in six cardiac regions by RNA-seq. Samples were donated from six subjects with or without persistent AF for left atria, left atrial appendages, right atria, sinoatrial nodes, left ventricles, right ventricles, and pulmonary veins (PVs), and additional four right atrial appendages samples were collected from patients undergoing mitral valve replacement. In total, 23 AF samples were compared to 23 non-AF samples. Surprisingly, the most influenced heart region in gene expression by AF was the PV, not the atria. The ion channel-related gene set was significantly enriched upon analysis of these significant genes. In addition, some significant genes are cancer-related lncRNAs in PV in AF. A co-expression network analysis could detect the functional gene clusters. In particular, the cancer-related lncRNA, such as SAMMSON and FOXCUT, belong to the gene network with the cancer-related transcription factor FOXC1. Thus, they may also play an aggravating role in the pathogenesis of AF, similar to carcinogenesis. In the least, this study suggests that (1) RNA alteration is most intense in PVs and (2) post-transcriptional gene regulation by lncRNA may contribute to the progression of AF. Through the screening analysis across the six cardiac regions, the possibility that the PV region can play a role other than paroxysmal triggering in the pathogenesis of AF was demonstrated for the first time. Future research with an increase in the number of PV samples will lead to a novel understanding of the pathophysiology of AF.
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肺静脈におけるカテコラミン誘発性不整脈の分子基盤
岡本 洋介
心電図 ( 日本不整脈心電学会誌 ) 40 ( 3 ) 141 - 148 2020年10月 [査読有り] [招待有り]
研究論文（学術雑誌） 単著
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Takagi D, Okamoto Y, Ohba T, Yamamoto H, Ono K
Journal of Physiological Sciences 70 ( 1 ) 2020年02月 [査読有り]
研究論文（学術雑誌） 国内共著
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Okamoto Y, Nagasawa Y, Obara Y, Ishii I, Takagi D, Ono K
Journal of Biological Chemistry 294 ( 44 ) 16049 - 16061 2019年11月 [査読有り]
研究論文（学術雑誌） 国内共著
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Umehara S, Tan X, Okamoto Y, Ono K, Noma A, Amano A, Himeno Y
International Journal of Molecular Sciences 20 ( 12 ) 2019年06月 [査読有り]
研究論文（学術雑誌） 国内共著
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ERK5 Phosphorylates Kv4.2 and Inhibits Inactivation of the A-Type Current in PC12 Cells.
Kashino Y, Obara Y, Okamoto Y, Saneyoshi T, Hayashi Y, Ishii K.
International journal of molecular science 2018年07月 [査読有り]
研究論文（学術雑誌） 国内共著
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The γ2 subunit of AMP-activated protein kinase regulates mammalian heart rate.
Yavari A, Bellahcene M, Bucchi A, Sirenko S, Pinter K, Herring N, Jung JJ, Tarasov KV, Sharpe EJ, Wolfien M, Czibik G, Steeples V, Ghaffari S, Nguyen C, Stockenhuber A, Clair JR, Rimmbach C, Okamoto Y, ,..& Ghaffari S.
Nature communication 2017年11月 [査読有り]
研究論文（学術雑誌） 国内共著
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Mammalian γ2 AMPK regulates intrinsic heart rate.
Arash Yavari, Mohamed Bellahcene, Annalisa Bucchi, Syevda Sirenko, Katalin Pinter, Neil Herring, Julia J Jung, Kirill V Tarasov, Emily J Sharpe, Markus Wolfien, Gabor Czibik, Violetta Steeples, Sahar Ghaffari, Chinh Nguyen, Alexander Stockenhuber, Joshua R St Clair, Christian Rimmbach, Yosuke Okamoto, Dongmei Yang, Mingyi Wang, Bruce D Ziman, Jack M Moen, Daniel R Riordon, Christopher Ramirez, Manuel Paina, Joonho Lee, Jing Zhang, Ismayil Ahmet, Michael G Matt, Yelena S Tarasova, Dilair Baban, Natasha Sahgal, Helen Lockstone, Rathi Puliyadi, Joseph de Bono, Owen M Siggs, John Gomes, Hannah Muskett, Mahon L Maguire, Youlia Beglov, Matthew Kelly, Pedro P N Dos Santos, Nicola J Bright, Angela Woods, Katja Gehmlich, Henrik Isackson, Gillian Douglas, David J P Ferguson, Jürgen E Schneider, Andrew Tinker, Olaf Wolkenhauer, Keith M Channon, Richard J Cornall, Eduardo B Sternick, David J Paterson, Charles S Redwood, David Carling, Catherine Proenza, Robert David, Mirko Baruscotti, Dario DiFrancesco, Edward G Lakatta, Hugh Watkins, Houman Ashrafian
Nature communications 8 ( 1 ) 1258 - 1258 2017年11月
研究論文（学術雑誌）
AMPK is a conserved serine/threonine kinase whose activity maintains cellular energy homeostasis. Eukaryotic AMPK exists as αβγ complexes, whose regulatory γ subunit confers energy sensor function by binding adenine nucleotides. Humans bearing activating mutations in the γ2 subunit exhibit a phenotype including unexplained slowing of heart rate (bradycardia). Here, we show that γ2 AMPK activation downregulates fundamental sinoatrial cell pacemaker mechanisms to lower heart rate, including sarcolemmal hyperpolarization-activated current (I f) and ryanodine receptor-derived diastolic local subsarcolemmal Ca2+ release. In contrast, loss of γ2 AMPK induces a reciprocal phenotype of increased heart rate, and prevents the adaptive intrinsic bradycardia of endurance training. Our results reveal that in mammals, for which heart rate is a key determinant of cardiac energy demand, AMPK functions in an organ-specific manner to maintain cardiac energy homeostasis and determines cardiac physiological adaptation to exercise by modulating intrinsic sinoatrial cell behavior.
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Deterioration of autonomic neuronal receptor signaling and mechanisms intrinsic to heart pacemaker cells contribute to age‐associated alterations in heart rate variability in vivo
Yaniv Y, Ahmet I, Tsutsui K, Behar J, Moen JM, Okamoto Y, Guiriba TR, Liu J, Bychkov R, Lakatta EG.
Aging cell 2016年08月 [査読有り]
研究論文（学術雑誌） 国内共著
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Stochasticity intrinsic to coupled-clock mechanisms underlie beat-to-beat variability of spontaneous action potential firing in sinoatrial node pacemaker cells.
Yaniv Y, Lyashkov AE, Sirenko S, Okamoto Y, Guiriba TR, Ziman BD, Morrell CH, Lakatta EG.
Jounal of molecular cellular cardiology 2014年12月
研究論文（学術雑誌） 国内共著
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Synchronization of sinoatrial node pacemaker cell clocks and its autonomic modulation impart complexity to heart beating intervals.
Yaniv Y, Ahmet I, Liu J, Lyashkov AE, Guiriba TR, Okamoto Y, Ziman BD, Lakatta EG.
Heart rhythm 2014年07月 [査読有り]
研究論文（学術雑誌） 国内共著
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Pathological impact of hyperpolarization- activated chloride current peculiar to rat pulmonary vein cardiomyocytes.
Okamoto Y, Kawamura K, Nakamura Y, Ono K.
Journal of molecular cellular cardiology 2014年01月 [査読有り]
研究論文（学術雑誌） 国内共著
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The mechanism of increased postnatal heart rate and sinoatrial node pacemaker activity in mice.
Adachi T, Shibata S, Okamoto Y, Sato S, Fujisawa S, Ohba T, Ono K.
Journal of physiological science 2013年03月 [査読有り]
研究論文（学術雑誌） 国内共著
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Down-regulation of L-type Ca2+ current in left atrial myocytes of rats during experimental cardiac hypertrophy
Zhang C, Okamoto Y, Ohba T, Ishibashi K, Yamamoto H, Ono K, Yamamoto F.
Akita J Med. 2012年12月 [査読有り]
研究論文（学術雑誌） 国内共著
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Arrhythmogenic coupling between the Na+ -Ca2+ exchanger and inositol 1,4,5-triphosphate receptor in rat pulmonary vein cardiomyocytes.
Okamoto Y, Takano M, Ohba T, Ono K.
Journal of molecular cellular cardiology 2012年05月 [査読有り]
研究論文（学術雑誌） 国内共著
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Direct effects of esmolol and landiolol on cardiac function, coronary vasoactivity, and ventricular electrophysiology in guinea-pig hearts
Shibata S, Okamoto Y, Endo S, Ono K.
Journal of pharmacological science 2012年02月 [査読有り]
研究論文（学術雑誌） 国内共著
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Identification and physiological activity of survival factor released from cardiomyocytes during ischaemia and reperfusion
Mizukami Y, Ono K, Du CK, Aki T, Hatano N, Okamoto Y, Ikeda Y, Ito H, Hamano K, Morimoto S.
Cardiovascular research 2008年07月 [査読有り]
研究論文（学術雑誌） 国内共著
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Sulfasalazine-induced hypersensitivity syndrome and hemophagocytic syndrome associated with reactivation of Epstein-Barr virus
Komatsuda A, Okamoto Y, Hatakeyama T, Wakui H, Sawada K.
Clinical Rheumatology 2008年05月 [査読有り]
研究論文（学術雑誌） 国内共著