Creation of the anti-aging therapy that assumed Apop gene as a target

2013 Fiscal Year Final Research Report

• Project/Area Number: 23590886
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General internal medicine (including Psychosomatic medicine)
• Research Institution: Kumamoto University
• Principal Investigator: YASUDA Osamu 熊本大学, 医学部附属病院, 准教授 (00372615)
• Co-Investigator(Kenkyū-buntansha): RAKUGI Hiromi 大阪大学, 医学(系)研究科(研究院), 教授 (20252679) ; FUKUO Keisuke 武庫川女子大学, 生活環境学部, 教授 (40156758)
• Co-Investigator(Renkei-kenkyūsha): YAMAMOTO Eiichirou 熊本大学, 医学部附属病院, 特任助教 (50573614)
• Project Period (FY): 2011 – 2013
• Keywords: 老年医学

Research Abstract

Apop gene was originally identified as a gene of unknown function in the atherosclerotic aorta. Functional analysis showed that Apop, a mitochondrial protein, gene expression affects the function of mitochondria. Mitochondria are intracellular organs that generate energy, oxidative stress, and contribute to cellular senescence. This study revealed that the Apop gene expression may regulate the cellular senescence.

Research Products

• [Journal Article] Tissue Inhibitor of Metalloproteinase-3 Knockout Mice Exhibit Enhanced Energy Expenditure through Thermogenesis (2014)
  • Author(s): Hanaoka Y, Yasuda O, Soejima H, Miyata K, Yamamoto E, Izumiya Y, Maeda N, Ohishi M, Rakugi H, Oike Y, Kim-Mitsuyama S, Ogawa H
  • Journal Title: PLoS One Volume: 9 Pages: e94930
  • DOI: 10.1371/journal.pone.0094930
  • Peer Reviewed
• [Journal Article] Correlation between extent of myocardial fibrosis assessed by cardiac magnetic resonance and cardiac troponin T release in patients with nonischemic heart failure (2014)
  • Author(s): Takashio S, Yamamuro M, Uemura T, Utsunomiya D, Morita K, Izumiya Y, Sugiyama S, Kojima S, Yamamoto E, Tsujita K, Tanaka T, Tayama S, Kaikita K, Hokimoto S, Yasuda O, Yamashita Y, Ogawa H
  • Journal Title: Am J Cardiol Volume: 113 Pages: 1697-1704
  • DOI: 10.1016/j.amjcard.2014.02.029
  • Peer Reviewed
• [Journal Article] Apoptosis signal-regulating kinase 1 is a novel target molecule for cognitive impairment induced by chronic cerebral hypoperfusion (2014)
  • Author(s): Toyama K, Koibuchi N, Uekawa K, Hasegawa Y, Kataoka K, Katayama T, Sueta D, Ma MJ, Nakagawa T, Yasuda O, Tomimoto H, Ichijo H, Ogawa H, Kim-Mitsuyama S
  • Journal Title: Arterioscler Thromb Vasc Biol Volume: 34 Pages: 616-625
  • DOI: 10.1161/ATVBAHA.113.302440
  • Peer Reviewed
• [Journal Article] Level of serum antibody against a periodontal pathogen is associated with atherosclerosis and hypertension (2013)
  • Author(s): Hanaoka Y, Soejima H, Yasuda O, Nakayama H, Nagata M, Matsuo K, Shinohara M, Izumi Y, Ogawa H
  • Journal Title: Hypertens Res Volume: 36 Pages: 829-833
  • DOI: 10.1038/hr.2013.46
  • Peer Reviewed
• [Journal Article] Novel mechanism for disrupted circadian blood pressure rhythm in a rat model of metabolic syndrome--the critical role of angiotensin II (2013)
  • Author(s): Sueta D, Kataoka K, Koibuchi N, Toyama K, Uekawa K, Katayama T, Mingjie M, Nakagawa T, Waki H, Maeda M, Yasuda O, Matsui K, Ogawa H, Kim-Mitsuyama S
  • Journal Title: J Am Heart Assoc Volume: 2 Pages: e000035
  • DOI: 10.1161/JAHA.113.000035
  • Peer Reviewed
• [Journal Article] Association of serum anti-periodontal pathogen antibody with ischemic stroke (2012)
  • Author(s): Hosomi N, Aoki S, Matsuo K, Deguchi K, Masugata H, Murao K, Ichihara N, Ohyama H, Dobashi H, Nezu T, Ohtsuki T, Yasuda O, Soejima H, Ogawa H, Izumi Y, Kohno M, Tanaka J, Matsumoto M
  • Journal Title: Cerebrovasc Dis Volume: 34 Pages: 385-392
  • DOI: 10.1159/000343659
  • Peer Reviewed
• [Journal Article] Calcium channel blockers, more than diuretics, enhance vascular protective effects of angiotensin receptor blockers in salt-loaded hypertensive rats (2012)
  • Author(s): Yamamoto E, Kataoka K, Dong YF, Koibuchi N, Toyama K, Sueta D, Katayama T, Yasuda O, Ogawa H, Kim-Mitsuyama S
  • Journal Title: PLoS One Volume: 7(6) Pages: e39162
  • DOI: 10.1371/journal.pone.0039162
  • Peer Reviewed
• [Journal Article] A novel Doppler echocardiographic score reflecting cardiac functional status can predict adverse outcome in acute myocardial infarction (2012)
  • Author(s): Fukuda Y, Fukuda N, Morishita S, Shinohara H, Yoshida H, Yasuda O, Shimoe Y, Tamura Y
  • Journal Title: J Echocardiogr Volume: 10 Pages: 41-47
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/22707909
  • Peer Reviewed
• [Journal Article] Amlodipine enhances amelioration of vascular insulin resistance, oxidative stress, and metabolic disorders by candesartan in metabolic syndrome rats (2012)
  • Author(s): Sueta D, Nakamura T, Dong YF, Kataoka K, Koibuchi N, Yamamoto E, Toyama K, Yasuda O, Ogawa H, Kim-Mitsuyama S
  • Journal Title: Am J Hypertens Volume: 25 (6) Pages: 704-710
  • DOI: 10.1038/ajh.2012.26
  • Peer Reviewed
• [Journal Article] CVD-associated non-coding RNA, ANRIL, modulates expression of atherogenic pathways in VSMC (2012)
  • Author(s): Congrains A, Kamide K, Katsuya T, Yasuda O, Oguro R, Yamamoto K, Ohishi M, Rakugi H
  • Journal Title: Biochem Biophys Res Commun Volume: 419 Pages: 612-616
  • DOI: 10.1016/j.bbrc.2012.02.050
  • Peer Reviewed
• [Journal Article] Case report of a long-surviving Werner syndrome patient with severe aortic valve stenosis (2012)
  • Author(s): Kawai T, Nozato Y, Kamide K, Onishi M, Yamamoto-Hanasaki H, Tatara Y, Takemura Y, Yamamoto K, Takeya Y, Sugimoto K, Kusakabe N, Yasuda O, Ohishi M, Rakugi H
  • Journal Title: Geriatr Gerontol Int Volume: 12 Pages: 174-175
  • DOI: 10.1111/j.1447-0594.2011.00748.x
  • Peer Reviewed
• [Journal Article] Genetic variants at the 9p21 locus contribute to atherosclerosis through modulation of ANRIL and CDKN2A/B (2012)
  • Author(s): Congrains A, Kamide K, Oguro R, Yasuda O, Miyata K, Yamamoto E, Kawai T, Kusunoki H, Yamamoto H, Takeya Y, Yamamoto K, Onishi M, Sugimoto K, Katsuya T, Awata N, Ikebe K, Gondo Y, Oike Y, Ohishi M, Rakugi H
  • Journal Title: Atherosclerosis Volume: 220 Pages: 449-455
  • DOI: 10.1016/j.atherosclerosis.2011.11.017
  • Peer Reviewed
• [Journal Article] Novel mechanism of angiotensin II-induced cardiac injury in hypertensive rats: the critical role of ASK1 and VEGF (2012)
  • Author(s): Nako H, Kataoka K, Koibuchi N, Dong YF, Toyama K, Yamamoto E, Yasuda O, Ichijo H, Ogawa H, Kim-Mitsuyama S
  • Journal Title: Hypertens Res Volume: 35 Pages: 194-200
  • DOI: 10.1038/hr.2011.175
  • Peer Reviewed
• [Journal Article] Passive exercise using whole-body periodic acceleration enhances blood supply to ischemic hindlimb (2011)
  • Author(s): Rokutanda T, Izumiya Y, Miura M, Fukuda S, Shimada K, Izumi Y, Nakamura Y, Araki S, Hanatani S, Matsubara J, Nakamura T, Kataoka K, Yasuda O, Kaikita K, Sugiyama S, Kim-Mitsuyama S, Yoshikawa J, Fujita M, Yoshiyama M, Ogawa H
  • Journal Title: Arterioscler Thromb Vasc Biol Volume: 31 Pages: 2872-2880
  • DOI: 10.1161/ATVBAHA.111.229773
  • Peer Reviewed
• [Journal Article] Crucial role of apoptogenic protein in cellular apoptosis and senescense (2011)
  • Author(s): Yamamoto E, Yasuda O, Fukuo K, Rakugi H, Ogihara T, Ogawa H
  • Journal Title: Nihon Ronen Igakkai Zasshi Volume: 48 Pages: 138-141
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/21778628
  • Peer Reviewed
• [Journal Article] Novel mechanism of salt-induced glomerular injury: critical role of eNOS and angiotensin II (2011)
  • Author(s): Nakamura T, Kataoka K, Tokutomi Y, Nako H, Toyama K, Dong YF, Koibuchi N, Yamamoto E, Yasuda O, Ogawa H, Kim-Mitsuyama S
  • Journal Title: J Hypertens Volume: 29 Pages: 1528-1535
  • DOI: 10.1097/HJH.0b013e328348ca95
  • Peer Reviewed
• [Journal Article] Telmisartan protects against diabetic vascular complications in a mouse model of obesity and type 2 diabetes, partially through peroxisome proliferator activated receptor-γ-dependent activity (2011)
  • Author(s): Toyama K, Nakamura T, Kataoka K, Yasuda O, Fukuda M, Tokutomi Y, Dong YF, Ogawa H, Kim-Mitsuyama S
  • Journal Title: Biochem Biophys Res Commun Volume: 410 Pages: 508-513
  • DOI: 10.1016/j.bbrc.2011.06.012
  • Peer Reviewed
• [Journal Article] Klotho protein diminishes endothelial apoptosis and senescence via a mitogen-activated kinase pathway (2011)
  • Author(s): Maekawa Y, Ohishi M, Ikushima M, Yamamoto K, Yasuda O, Oguro R, Yamamoto-Hanasaki H, Tatara Y, Takeya Y, Rakugi H
  • Journal Title: Geriatr Gerontol Int Volume: 11 Pages: 510-516
  • DOI: 10.1111/j.1447-0594.2011.00699.x
  • Peer Reviewed
• [Journal Article] Eplerenone potentiates protective effects of amlodipine against cardiovascular injury in salt-sensitive hypertensive rats (2011)
  • Author(s): Nakamura T, Fukuda M, Kataoka K, Nako H, Tokutomi Y, Dong YF, Yamamoto E, Yasuda O, Ogawa H, Kim-Mitsuyama S
  • Journal Title: Hypertens Res Volume: 34 Pages: 817-824
  • DOI: 10.1038/hr.2011.35
  • Peer Reviewed
• [Journal Article] 正常血圧者の降圧療法による心血管病二次予防効果 (2011)
  • Author(s): 安田修、小川久雄
  • Journal Title: 血圧 Volume: 18 Pages: 1186-1187
  • URL: http://mol.medicalonline.jp/library/journal/abstract?GoodsID=ae6keatd/2011/001812/004&name=1186-1187j&UserID=133.95.81.49
• [Journal Article] メタボリックシンドローム患者の加齢による血圧変化 (2011)
  • Author(s): 安田修
  • Journal Title: 血圧 Volume: 18 Pages: 520-521
  • URL: http://mol.medicalonline.jp/library/journal/abstract?GoodsID=ae6keatd/2011/001806/002&name=0520-0521j&UserID=133.95.81.49
• [Presentation] Apoptogenic Protein is a Novel Phenotypic Marker of the Contractile Vascular Smooth Muscle Cells (2014)
  • Author(s): 安田 修
  • Organizer: 第78回日本循環器学会学術集会
  • Place of Presentation: 東京、東京国際フォーラム
  • Year and Date: 20140321-23
• [Presentation] Apop Inhibition Reduces Inflammation after Cerebral Ischemi (2014)
  • Author(s): 安田 修
  • Organizer: 第78回日本循環器学会学術集会
  • Place of Presentation: 東京、東京商工会議所
  • Year and Date: 20140321-23
• [Presentation] Timp-3 Deficiency Increases Energy Expenditure and Thermogenesis in Mice (2014)
  • Author(s): 花岡 洋右
  • Organizer: 第78回日本循環器学会学術集会
  • Place of Presentation: 東京、東京国際フォーラム
  • Year and Date: 20140321-23
• [Presentation] Apop 遺伝子抑制と血管内皮細胞傷害 (2013)
  • Author(s): 安田 修
  • Organizer: 第61回日本心臓病学会学術集会
  • Place of Presentation: 熊本、熊本市現代美術館
  • Year and Date: 20130920-22
• [Presentation] Timp-3欠損はマウスのミトコンドリア代謝に影響を与える (2013)
  • Author(s): 花岡 洋右
  • Organizer: 第61回日本心臓病学会学術集会
  • Place of Presentation: 熊本、熊本市現代美術館
  • Year and Date: 20130920-22
• [Presentation] Apop 遺伝子発現制御による認知機能低下の抑制 (2013)
  • Author(s): 安田 修
  • Organizer: 第55回日本老年医学会学術集会
  • Place of Presentation: 大阪、大阪国際会議場
  • Year and Date: 20130604-06
• [Presentation] Timp-3 欠損はマウスの代謝に影響を与える (2013)
  • Author(s): 花岡洋右
  • Organizer: 第55回日本老年医学会学術集会
  • Place of Presentation: 大阪、大阪国際会議場
  • Year and Date: 20130604-06
• [Presentation] Apop is a Novel Therapeutic Target for the Prevention of Impaired Cognitive Function after Cerebral Ischemia (2013)
  • Author(s): 安田 修
  • Organizer: 第77回日本循環器学会学術集会
  • Place of Presentation: 神奈川、パシフィコ横浜
  • Year and Date: 20130315-17
• [Presentation] Apop Gene Inhibition Induces Reactive Oxygen Species Production and Dysfunction of Vascular Endothelial Cells (2013)
  • Author(s): 安田 修
  • Organizer: 第77回日本循環器学会学術集会
  • Place of Presentation: 神奈川、パシフィコ横浜
  • Year and Date: 20130315-17
• [Presentation] Tissue Inhibitor of Metalloproteinse-3 Deficiency Enhances Metabolism in Mice (2013)
  • Author(s): 花岡洋右
  • Organizer: 第77回日本循環器学会学術集会
  • Place of Presentation: 神奈川、パシフィコ横浜
  • Year and Date: 20130315-17
• [Presentation] 歯周病と動脈硬化および高血圧との関連 (2012)
  • Author(s): 花岡洋右
  • Organizer: 第1回高血圧フォーラム
  • Place of Presentation: 大阪、千里ライフサイエンスセンター
  • Year and Date: 20120512-13
• [Presentation] Apop Gene Expression is Implicated in Senescence of Vascular Endothelial Cells Induced by High Glucose (2012)
  • Author(s): 安田 修
  • Organizer: 第76回日本循環器学会学術集会
  • Place of Presentation: 福岡、福岡国際会議場
  • Year and Date: 20120316-18
• [Presentation] Implication of Apop, a Novel Mitochondrial Protein, in the Mitochondrial Oxidative Stress Production (2012)
  • Author(s): 安田 修
  • Organizer: 第76回日本循環器学会学術集会
  • Place of Presentation: 福岡、福岡国際会議場
  • Year and Date: 20120316-18
• [Remarks]
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