The mechanism for blood pressure elevation in newly developed obesity mouse and the application for the prevention and treatment of hypertension

• Project/Area Number: 22500656
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied health science
• Research Institution: University of Tsukuba
• Principal Investigator: SAKAI Satoshi 筑波大学, 医学医療系, 講師 (30282362)
• Co-Investigator(Kenkyū-buntansha): ISHII Tetsuro 筑波大学, 医学医療系, 教授 (20111370) ; SHIMOJO Nobutake 筑波大学, 医学医療系, 講師 (20462210)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 肥満 / 高血圧 / SQSTM1 / 生活習慣病 / レプチン

Research Abstract

We generated conventional knockout mice (KO) of sequestosome1/A170, the molecule related to oxidative stress. KO exhibited the phenotype of obesity and impaired glucose tolerance due to hyperphagia and leptin resistance. We evaluated hemodynamics by telemetry system under no restrictions. During resting time, blood pressure (BP) and pulse rate was higher in KO compared to wild type (WT) though it did not differ during active time, indicating that KO shows the BP pattern of non-dipper type of hypertension. The urine amount of excreted catecholamine was significantly higher in KO than WT, suggesting that increase of the sympathetic nerve activity contributes to the BP elevation in KO.

Research Products

• [Journal Article] Endothelin-1-induced cardiomyocyte hypertrophy is partly regulated by transcription factor II-F interacting C-terminal domain phosphatase of RNA polymerase II (2012)
  • Author(s): Sakai S, Kimura T, Wang Z, Shimojo N, Maruyama H, Homma S, Kuga K, Yamaguchi I, Aonuma K, Miyauchi T
  • Journal Title: Life Sci Volume: 91 Pages: 572-7
  • Peer Reviewed
• [Journal Article] Increased plasma levels of big-endothelin-2 and big-endothelin-3 in patients with end-stage renal disease (2012)
  • Author(s): Miyauchi Y, Sakai S, Maeda S, Shimojo N, Watanabe S, Homma S, Kuga K, Aonuma K, Miyauchi T
  • Journal Title: Life Sci. Volume: 91 Pages: 729-32
  • Peer Reviewed
• [Journal Article] Suppressor of cytokine signaling 1 DNA administration inhibits inflammatory and pathogenic responses in autoimmune myocarditis (2012)
  • Author(s): Tajiri K, Imanaka-Yoshida K, Matsubara A, Tsujimura Y, Hiroe M, Naka T, Shimojo N, Sakai S, Aonuma K, Yasutomi Y.
  • Journal Title: J Immunol. Volume: 189 Pages: 2043-53
  • Peer Reviewed
• [Journal Article] Prognostic value of serum tenascin-C levels on long-term outcome after acute myocardial infarction (2012)
  • Author(s): Sato A, Hiroe M, Akiyama D, Hikita H, Nozato T, Hoshi T, Kimura T, Wang Z, Sakai S, Imanaka-Yoshida K, Yoshida T, Aonuma K
  • Journal Title: J Card Fail. Volume: 18 Pages: 480-6
  • Peer Reviewed
• [Journal Article] Nrf2 inhibits hepatic iron accumulation and counteracts oxidative stress-induced liver injury in nutritional steatohepatitis. (2012)
  • Author(s): Okada K, Warabi E, Sugimoto H, Horie M, Tokushige K, Ueda T, Harada N, Taguchi K, Hashimoto E, Itoh K, Ishii T, Utsunomiya H, Yamamoto M, Shoda J
  • Journal Title: J Gastroenterol Volume: 47 Pages: 927-35
  • NAID: 10031051379
• [Journal Article] Novel roles of peroxiredoxins in inflammation, cancerand innate immunity. (2012)
  • Author(s): Ishii T, Warabi E, Yanagawa T.
  • Journal Title: J Clin Biochem Nutr. Volume: 50 Pages: 91-105
  • Peer Reviewed
• [Journal Article] Endothelin-1-induced cardiomyocyte hypertrophy is partly regulated by transcription factor II-F interacting C-terminal domain phosphatase of RNA polymerase II (2012)
  • Author(s): Sakai S
  • Journal Title: Life Sciences Volume: 91 Issue: 13-14 Pages: 572-577
  • DOI: 10.1016/j.lfs.2012.04.034
  • Peer Reviewed
• [Journal Article] Novel roles of peroxiredoxins in inflammation, cancer and innate immunity (2012)
  • Author(s): Ishii T
  • Journal Title: Journal of Clinical Biochemistry and Nutrition Volume: 50 Issue: 2 Pages: 91-105
  • DOI: 10.3164/jcbn.11-109
  • NAID: 130004466687
  • ISSN: 0912-0009, 1880-5086
  • Peer Reviewed
• [Journal Article] Suppressor of cytokine signaling 1 (SOCS1) DNA administration inhibits inflammatory and pathogenic responses in autoimmune myocarditis (2012)
  • Author(s): Tajiri K
  • Journal Title: Journal of Immunology Volume: 189 Issue: 4 Pages: 2043-2053
  • DOI: 10.4049/jimmunol.1103610
  • Peer Reviewed
• [Journal Article] Nrf2 inhibits hepatic iron accumulation and counteracts oxidative stress-induced liver injury in nutritional steatohepatitis (2012)
  • Author(s): Okada K, Warabi E, Sugimoto H, Horie M, Tokushige K, Ueda T, Harada N, Taguchi K, Hashimoto E, Itoh K, Ishii T, Utsunomiya H, Yamamoto M, Shoda J
  • Journal Title: J.Gastroenterol Volume: (印刷中) Issue: 8 Pages: 924-935
  • DOI: 10.1007/s00535-012-0552-9
  • NAID: 10031051379
  • Peer Reviewed
• [Journal Article] Prediction of Chronic Renal Insufficiency after Coronary Angiography by an Early Increase in Oxidative Stress and Decrease in Glomerular Filtration Rate (2011)
  • Author(s): Tajiri K, Maruyama H, Sato A, Shimojo N, Endo M, Aihara H, Kawano S, Watanabe S, Sakai S, Aonuma K.
  • Journal Title: Circ J Volume: 75 Pages: 437-442
  • NAID: 10027427336
  • Peer Reviewed
• [Journal Article] Protective role of Nrf2 in age-related hearing loss and gentamicin ototoxicity (2011)
  • Author(s): Hoshino T, Tabuchi K, Nishimura B, Tanaka S, Nakayama M, Ishii T, Warabi E, Yanagawa T, Shimizu R, Yamamoto M, Hara A.
  • Journal Title: Biochem Biophys Res Commun Volume: 415 Pages: 94-8
  • NAID: 120007137353
  • Peer Reviewed
• [Journal Article] Aggravation of bleomycin-induced pulmonary inflammation and fibrosis in mice lacking peroxiredoxin I (2011)
  • Author(s): Kikuchi N, Ishii Y, Morishima Y, Yageta Y, Haraguchi N, Yamadori T, Masuko H, Sakamoto T, Yanagawa T, Warabi E, Ishii T, Hizawa N
  • Journal Title: Am J Respir Cell Mol Biol Volume: 45 Pages: 600-9
  • Peer Reviewed
• [Journal Article] Prediction of Chronic Renal Insufficiency After Coronary Angiography by an Early Increase in Oxidative Stress and Decrease in Glomerular Filtration Rate (2011)
  • Author(s): Tajiri K, Sakai K, et al.
  • Journal Title: Circulation Journal Volume: 75 Issue: 2 Pages: 437-442
  • DOI: 10.1253/circj.CJ-10-0622
  • NAID: 10027427336
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed
• [Journal Article] Prediction of chronic renal insufficiency after coronary angiography by an early increase in oxidative stress and decrease in glomerular filtration rate. (2011)
  • Author(s): Tajiri K, Shimojo N, Sakai S., 他8名
  • Journal Title: Circulation Journal Volume: VOL.75 Pages: 437-442
  • NAID: 10027427336
  • Peer Reviewed
• [Journal Article] Aggravation of bleomycin-induced pulmonary inflammation and fibrosis in mice lacking peroxiredoxin 1. (2011)
  • Author(s): Kiuchi N, Ishii T, 他10名
  • Journal Title: American Journal of Cell and Molecular Biology Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Enhanced neointimal hyperplasia and carotid artery remodelling in sequestosome 1 deficient mice (2010)
  • Author(s): Sugimoto R, Warabi E, Katayanagi S, Sakai S, Uwayama J, Yanagawa T, Watanabe A, Harada H, Kitamura K, Noguchi N, Yoshida H, Siow RC, Mann GE, Ishii T
  • Journal Title: J Cell Mol Med Volume: 14 Pages: 1546-54
  • Peer Reviewed
• [Journal Article] Cochlear protection from acoustic injury by inhibitors of p38 mitogen-activated protein kinase and sequestosome 1 stress protein (2010)
  • Author(s): Tabuchi K, Oikawa K, Hoshino T, Nishimura B, Hayashi K, Yanagawa T, Warabi E, Ishii T, Tanaka S, Hara A
  • Journal Title: Neuroscience Volume: 166 Pages: 665-70
  • Peer Reviewed
• [Journal Article] Deletion of nuclear factor-E2-related factor-2 leads to rapid onset and progression of nutritional steatohepatitis in mice. (2010)
  • Author(s): Sugimoto H, Okada K, Shoda J, Warabi E, Ishige K, Ueda T, Taguchi K, Yanagawa T, Nakahara A, Hyodo I, Ishii T, Yamamoto M
  • Journal Title: Am J Physiol Gastrointest Liver Physiol Volume: 298
  • Peer Reviewed
• [Journal Article] Physician-pharmacist cooperation program for blood pressure control in patients with hypertension: a randomized-controlled trial. (2010)
  • Author(s): Tobari H, Arimoto T, Shimojo N, Yuhara K, Noda H, Yamagishi K, Iso H
  • Journal Title: Am J Hypertens Volume: 23 Pages: 1144-52
  • NAID: 120007130950
  • Peer Reviewed
• [Journal Article] Additive beneficial effects of lactotripeptides intake with regular exercise on endothelium-dependent dilatation in postmenopausal women. (2010)
  • Author(s): Yoshizawa M, Maeda S, Miyaki A, Misono M, Choi Y, Shimojo N, Ajisaka R, Tanaka H.
  • Journal Title: Am J Hypertens Volume: 23 Pages: 368-72
  • Peer Reviewed
• [Journal Article] Is pentraxin 3 involved in obesity-induced decrease in arterial distensibility (2010)
  • Author(s): Miyaki A, Maeda S, Yoshizawa M, Misono M, Sasai H, Shimojo N, Tanaka K, Ajisaka R.
  • Journal Title: J Atheroscler Thromb Volume: 17 Pages: 278-84
  • NAID: 130004444420
  • Peer Reviewed
• [Journal Article] Enhanced neointimal hyperplasia and carotid artery remodeling in sequestosome 1 deficient mice. (2010)
  • Author(s): Sugimoto R, Sakai S, Ishii T., 他11名
  • Journal Title: Journal of Cellular and Molecular Medicine Volume: VOL.14 Pages: 1546-1554
  • Peer Reviewed
• [Presentation] Roles of sequestosome1/p62 in prevention of obesity, hypertension and atherosclerosis (2012)
  • Author(s): Ishii T, Warabi E, Sakai S, Yanagawa T
  • Organizer: The 16th Society for Free Radical Research International Biennial Meeting
  • Place of Presentation: London, UK
  • Year and Date: 2012-09-09
• [Presentation] Protective Activity to Oxydative Stress is Attenuated in Development of Angiotensin II-Induced Cardiac Fibrosis and Dysfunction (2012)
  • Author(s): Sakai S, Warabi E, Kimura T, Miyauchi T, Aonuma K, Ishii T
  • Organizer: The 16th Society for Free Radical Research International Biennial Meeting.
  • Place of Presentation: London, UK
  • Year and Date: 2012-09-08
• [Presentation] Cardiomyocyte hypertrophy incuded by endothelin-1 is regulated by transcription factor II-F interacting C-terminal domain phosphatase (FCP1) of RNA polymerase II (2011)
  • Author(s): Sakai S, Homma S, Aonuma K, Miyauchi T
  • Organizer: The 12th International Conference on Endothelin
  • Place of Presentation: Cambridge, UK
  • Year and Date: 2011-09-14
• [Presentation] Non-dipper-like hypertension in sequestosome1/p62/A170 deficient mice in early phase of obesity (2011)
  • Author(s): Warabi E, Sakai S, Suzuki E, Tomoo T, Yanagawa T, Mann GE, Ishii T
  • Organizer: Physiology
  • Place of Presentation: Oxford, UK
  • Year and Date: 2011-07-13
• [Presentation] Non-dipper-like hypertension in sequestosome1/p62/A170 deficient mice in early phase of obesity (2011)
  • Author(s): Warabi E, Sakai S, et al.
  • Organizer: Physiology 2011
  • Place of Presentation: Oxford, UK
  • Year and Date: 2011-07-13
• [Presentation] Possible involvement of SREBP-1 in the cardiac dysfunction via reduction of antioxidant gene (2010)
  • Author(s): Sakai S, Shimojo N, 他4名
  • Organizer: XXth World Congress of the International Society for Heart Research
  • Place of Presentation: 京都国際会議場(京都)
  • Year and Date: 2010-05-16
• [Presentation] Deficiency of sequestosome1/p62/A170 in mice is associated with metabolic syndrome: (II)Enhanced neointimal hyperplasia and carotid artery remodeling. (2010)
  • Author(s): Warabi E, Sakai S, Yanagawa T, Harada H, Siow RCM, Mann GE, Ishii T
  • Organizer: Enhanced neointimal hyperplasia and carotid artery remodeling.
  • Place of Presentation: Salamanca, Spain
  • Year and Date: 2010-05-01
• [Presentation] Deficiency of sequestosome1/p62/A170 in mice is associated with metabolic syndrome: (III) Non- dipper type hypertension (2010)
  • Author(s): Warabi E, Sakai S, Suzuki E, Tomoo T, Tomoike S, Enomoto Y, Harada H,Yanagawa T, Mann GE, Ishii T
  • Organizer: International Symposium on the Pathophysiology of Reactive Oxygen and Nitrogen Species
  • Place of Presentation: Salamanca, Spain
  • Year and Date: 2010-05-01
• [Presentation] Roles of sequestosome1/p62 in prevention of obesity, hypertension and atherosclerosis.
  • Author(s): Ishii T
  • Organizer: The 16th Society for Free Radical Research International Biennial Meeting 2012
  • Place of Presentation: Imperial college of London (London, UK)
  • Invited
• [Book] 副腎皮質ステロイド合併症としてみられる病態--高血圧-- 小池隆夫、住田孝之編「GUIDELINE 膠原病・リウマチ --治療ガイドラインをどう読むか-- 第2版」 (2010)
  • Author(s): 酒井 俊・河野 了・青沼和隆
  • Publisher: 診断と治療社
• [Book] 肺高血圧モデル「シリーズモデル動物利用マニュアル・疾患モデルの作製と利用-循環器疾患」ANIMAL MODELS (2010)
  • Author(s): 前田清司・宮内裕美・酒井 俊・宮 内 卓 北 徹、堀内久徳、柳田素子、猪原匡史、冨本秀和、並河 徹編
  • Publisher: Life-Science Information Center社
• [Book] 副腎皮質ステロイド合併症としてみられる病態-高血圧-(分担)GUIDELINE膠原病・リウマチ 治療ガイドラインをどう読むか 第2版 (2010)
  • Author(s): 酒井俊, 他2名
  • Total Pages: 8
  • Publisher: 診断と治療社