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

Research Project

Project/Area Number 22500656
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied health science
Research InstitutionUniversity 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 *help
¥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.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (35 results)

All 2012 2011 2010 Other

All Journal Article (23 results) (of which Peer Reviewed: 22 results) Presentation (9 results) (of which Invited: 1 results) Book (3 results)

  • [Journal Article] Endothelin-1-induced cardiomyocyte hypertrophy is partly regulated by transcription factor II-F interacting C-terminal domain phosphatase of RNA polymerase II2012

    • 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

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Increased plasma levels of big-endothelin-2 and big-endothelin-3 in patients with end-stage renal disease2012

    • 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

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Suppressor of cytokine signaling 1 DNA administration inhibits inflammatory and pathogenic responses in autoimmune myocarditis2012

    • 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

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Prognostic value of serum tenascin-C levels on long-term outcome after acute myocardial infarction2012

    • 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

    • Related Report
      2012 Final Research Report
    • 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

    • Related Report
      2012 Final Research Report
  • [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

    • Related Report
      2012 Final Research Report
    • 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 II2012

    • Author(s)
      Sakai S
    • Journal Title

      Life Sciences

      Volume: 91 Issue: 13-14 Pages: 572-577

    • DOI

      10.1016/j.lfs.2012.04.034

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel roles of peroxiredoxins in inflammation, cancer and innate immunity2012

    • 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
    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Suppressor of cytokine signaling 1 (SOCS1) DNA administration inhibits inflammatory and pathogenic responses in autoimmune myocarditis2012

    • Author(s)
      Tajiri K
    • Journal Title

      Journal of Immunology

      Volume: 189 Issue: 4 Pages: 2043-2053

    • DOI

      10.4049/jimmunol.1103610

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nrf2 inhibits hepatic iron accumulation and counteracts oxidative stress-induced liver injury in nutritional steatohepatitis2012

    • 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

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prediction of Chronic Renal Insufficiency after Coronary Angiography by an Early Increase in Oxidative Stress and Decrease in Glomerular Filtration Rate2011

    • 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

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Protective role of Nrf2 in age-related hearing loss and gentamicin ototoxicity2011

    • 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

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Aggravation of bleomycin-induced pulmonary inflammation and fibrosis in mice lacking peroxiredoxin I2011

    • 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

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Prediction of Chronic Renal Insufficiency After Coronary Angiography by an Early Increase in Oxidative Stress and Decrease in Glomerular Filtration Rate2011

    • 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
    • Related Report
      2011 Annual Research Report
    • 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

    • Related Report
      2010 Annual Research Report
    • 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

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enhanced neointimal hyperplasia and carotid artery remodelling in sequestosome 1 deficient mice2010

    • 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

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cochlear protection from acoustic injury by inhibitors of p38 mitogen-activated protein kinase and sequestosome 1 stress protein2010

    • 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

    • Related Report
      2012 Final Research Report
    • 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

    • Related Report
      2012 Final Research Report
    • 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

    • Related Report
      2012 Final Research Report
    • 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

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Is pentraxin 3 involved in obesity-induced decrease in arterial distensibility2010

    • 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

    • Related Report
      2012 Final Research Report
    • 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

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Roles of sequestosome1/p62 in prevention of obesity, hypertension and atherosclerosis2012

    • 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
    • Related Report
      2012 Final Research Report
  • [Presentation] Protective Activity to Oxydative Stress is Attenuated in Development of Angiotensin II-Induced Cardiac Fibrosis and Dysfunction2012

    • 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
    • Related Report
      2012 Final Research Report
  • [Presentation] Cardiomyocyte hypertrophy incuded by endothelin-1 is regulated by transcription factor II-F interacting C-terminal domain phosphatase (FCP1) of RNA polymerase II2011

    • 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
    • Related Report
      2012 Final Research Report
  • [Presentation] Non-dipper-like hypertension in sequestosome1/p62/A170 deficient mice in early phase of obesity2011

    • 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
    • Related Report
      2012 Final Research Report
  • [Presentation] Non-dipper-like hypertension in sequestosome1/p62/A170 deficient mice in early phase of obesity2011

    • Author(s)
      Warabi E, Sakai S, et al.
    • Organizer
      Physiology 2011
    • Place of Presentation
      Oxford, UK
    • Year and Date
      2011-07-13
    • Related Report
      2011 Annual Research Report
  • [Presentation] Possible involvement of SREBP-1 in the cardiac dysfunction via reduction of antioxidant gene2010

    • 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
    • Related Report
      2010 Annual Research Report
  • [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
    • Related Report
      2012 Final Research Report
  • [Presentation] Deficiency of sequestosome1/p62/A170 in mice is associated with metabolic syndrome: (III) Non- dipper type hypertension2010

    • 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
    • Related Report
      2012 Final Research Report
  • [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)
    • Related Report
      2012 Annual Research Report
    • 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
    • Related Report
      2012 Final Research Report
  • [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 MODELS2010

    • 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
    • Related Report
      2012 Final Research Report
  • [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
    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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