Analysis of the ageing mechanism induced by Apop

2012 Fiscal Year Final Research Report

• Project/Area Number: 21390222
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General internal medicine (including Psychosomatic medicine)
• Research Institution: Osaka University
• Principal Investigator: RAKUGI Hiromi 大阪大学, 医学系研究科, 教授 (20252679)
• Co-Investigator(Kenkyū-buntansha): YASUDA Osamu 熊本大学, 医学部附属病院, 准教授 (00372615) ; 福尾 惠介 武庫川女子大学, 生活環境学部, 教授 (40156758)
• Project Period (FY): 2009 – 2012
• Keywords: 老化 / ミトコンドリア

Research Abstract

We found that the expression of Apoptogenic Protein (Apop) is implicated in oxidative stress production and senescence of cells. In addition, we found that Apop expression affected the activation of mitochondrial metabolism. Apop gene inhibition enhance fatty acid metabolism, and improved serum cholesterol level and body weight. Therefore, Apop could be to a novel therapeutic target for the treatment of dyslipidemia and obesity.

Research Products

• [Journal Article] Molecular Mechanisms and Implications in Human Health (2013)
  • Author(s): Congrains A, Kamide K, Ohishi M, Rakugi H. ANRIL
  • Journal Title: nt J Mol Sci. Volume: 14 Pages: 1278-1292
  • Peer Reviewed
• [Journal Article] Angiotensin (1-7) and other AngiotensinPeptides. (2013)
  • Author(s): Ohishi M, Yamamoto K, Rakugi H.
  • Journal Title: Curr Pharm Des Volume: 19 Pages: 3060-3064
  • Peer Reviewed
• [Journal Article] Analysis ofhepatic gene expression profile in a spontaneous mouse model of type 2 diabetes under a high sucrose diet (2013)
  • Author(s): Nojima K, Sugimoto K, Ueda H, Babaya N, Ikegami H, Rakugi H.
  • Journal Title: Endocr J. Volume: 60 Pages: 261-274
  • Peer Reviewed
• [Journal Article] Loss of ACE2 exaggerates high-calorie diet-induced insulin resistance by reduction of GLUT4 in mice. (2013)
  • Author(s): Takeda M, Yamamoto K, Takemura Y, Takeshita H, Hongyo K, Kawai T,Hanasaki-Yamamoto H, Oguro R, Takami Y, Tatara Y, Takeya Y, Sugimoto K, Kamide K, Ohishi M, Rakugi H.
  • Journal Title: Diabetes. Volume: 62 Pages: 223-233
  • Peer Reviewed
• [Journal Article] Influence of renin angiotensin system gene polymorphisms onvisit-to-visit blood pressure variability in hypertensive patients. (2012)
  • Author(s): Kawai T, Ohishi M, Onishi M, Takeya Y, Ito N, Kato N, Yamamoto K, Kamide K,Rakugi H.
  • Journal Title: Am J Hypertens. Volume: 25 Pages: 1249-1255
  • Peer Reviewed
• [Journal Article] Maxacalcitol ameliorates tubulointerstitial fibrosis in obstructed kidneys by recruiting PPM1A/VDR complex to pSmad3. (2012)
  • Author(s): Inoue K, Matsui I, Hamano T, Fujii N, Shimomura A, Nakano C, Kusunoki Y,Takabatake Y, Hirata M, Nishiyama A, Tsubakihara Y, Isaka Y, Rakugi H.
  • Journal Title: Lab Invest. Volume: 92 Pages: 1686-1697
  • Peer Reviewed
• [Journal Article] Pharmacogenomic approaches to study the effects of antihypertensive drugs. (2012)
  • Author(s): Kamide K, Kawano Y, Rakugi H.
  • Journal Title: Hypertens Res. Volume: 35 Pages: 796-799
  • Peer Reviewed
• [Journal Article] Relationship between renal hemodynamic status and aging in patients without diabetes evaluated by renal Doppler ultrasonography. (2012)
  • Author(s): Kawai T, Kamide K, Onishi M, Hongyo K, Yamamoto-Hanasaki H, Oguro R, Maekawa Y, Yamamoto K, Takeya Y, Sugimoto K, Ohishi M, Rakugi H.
  • Journal Title: Clin Exp Nephrol. Volume: 16 Pages: 786-791
  • Peer Reviewed
• [Journal Article] CVD-associated non-coding RNA, ANRIL, modulates expression ofatherogenic 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
  • Peer Reviewed
• [Journal Article] Combined use of vitamin D status andFGF23 for risk stratification of renal outcome. (2012)
  • Author(s): Nakano C, Hamano T, Fujii N, Matsui I, Tomida K, Mikami S, Inoue K, Obi Y,Okada N, Tsubakihara Y, Isaka Y, Rakugi H.
  • Journal Title: Clin J Am Soc Nephrol. Volume: 7 Pages: 810-819
  • Peer Reviewed
• [Journal Article] Use of xanthine oxidase inhibitor febuxostat inhibits renal interstitial inflammation and fibrosis in unilateral ureteral obstructive nephropathy. (2012)
  • Author(s): Omori H, Kawada N, Inoue K, Ueda Y, Yamamoto R, Matsui I, Kaimori J,Takabatake Y, Moriyama T, Isaka Y, Rakugi H.
  • Journal Title: Clin Exp Nephrol. Volume: 16 Pages: 549-556
  • Peer Reviewed
• [Journal Article] Autophagy guards against cisplatin-induced acutekidney injury. (2012)
  • Author(s): Takahashi A, Kimura T, Takabatake Y, Namba T, Kaimori J, Kitamura H, Matsui I, Niimura F, Matsusaka T, Fujita N, Yoshimori T, Isaka Y, Rakugi H.
  • Journal Title: Am J Pathol. Volume: 180 Pages: 517-525
  • Peer Reviewed
• [Journal Article] A single nucleotide polymorphism of the adenosine deaminase, RNA-specific gene isassociated with the serum triglyceride level, abdominal circumference, and serum adiponectin concentration. (2012)
  • Author(s): Oguro R, Kamide K, Katsuya T, Akasaka H, Sugimoto K, Congrains A, Arai Y, Hirose N, Saitoh S, Ohishi M, Miura T, Rakugi H.
  • Journal Title: Exp Gerontol. Volume: 47 Pages: 183-187
  • 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
  • Peer Reviewed
• [Journal Article] Gene polymorphisms contributing to hypertension in immunoglobulin Anephropathy. (2012)
  • Author(s): Shinzawa M, Y amamoto R, Nagasawa Y, Shoji T, Obi Y, Namba T, Kitamura H,Kaneko T, Okada N, Iwatani H, Yamauchi A, Tsubakihara Y, Imai E, Isaka Y, Rakugi H.
  • Journal Title: Clin Exp Nephrol. Volume: 16 Pages: 250-258
  • Peer Reviewed
• [Journal Article] Angiotensin-converting enzyme single nucleotide polymorphism is a genetic riskfactor for cardiovascular disease: a cohort study of hypertensive patients. (2011)
  • Author(s): Kato N, Tatara Y, Ohishi M, Takeya Y, Onishi M, Maekawa Y, Rakugi H.
  • Journal Title: Hypertens Res Volume: 34 Pages: 728-734
  • Peer Reviewed
• [Journal Article] Usefulness of the resistive index in renal Doppler ultrasonography as an indicator of vascular damage in patients with risks of atherosclerosis. (2011)
  • Author(s): Kawai T, Kamide K, Onishi M, Yamamoto-Hanasaki H, Baba Y, Hongyo K, Shimaoka I, Tatara Y, Takeya Y, Ohishi M, Rakugi H.
  • Journal Title: Nephrol Dial Transplant. Volume: 26 Pages: 3256-3262
  • Peer Reviewed
• [Journal Article] Impact of concomitant diabetes and chronic kidney disease on preload-induced changes in left ventricular diastolic filling in hypertensive patients. (2011)
  • Author(s): Iwashima Y, Horio T, Suzuki Y, Takagi T, Kamide K, Ohishi M, Ogihara T, Yoshikawa J, Kawano Y, Rakugi H.
  • Journal Title: J Hypertens Volume: 29 Pages: 144-153
  • Peer Reviewed
• [Journal Article] Urinary type IV collagen in nondiabetic kidney disease. (2011)
  • Author(s): Furumatsu Y, Nagasawa Y, Shoji T, Yamamoto R, Iio K, Matsui I, Takabatake Y, Kaimori JY, Iwatani H, Kaneko T, Tsubakihara Y, Imai E, Isaka Y, Rakugi H.
  • Journal Title: Nephron Clin Pract. Volume: 117 Pages: c160-c166
  • Peer Reviewed
• [Journal Article] Promoter Polymorphism of RGS2 Gene Is Associated with Change of Blood Pressure in Subjects with Antihypertensive Treatment: The Azelnidipine and Temocapril in Hypertensive Patients with Type 2 Diabetes Study. (2010)
  • Author(s): Sugimoto K, Katsuya T, Kamide K, Fujisawa T, Shimaoka I, Ohishi M, Morishita R, Ogihara T, Rakugi H.
  • Journal Title: Int J Hypertens Volume: 2010 Pages: 196307
  • Peer Reviewed
• [Journal Article] Strong suppression of the renin-angiotensin system has arenal-protective effect in hypertensive patients: high-dose ARB with ACEinhibitor (Hawaii) study. (2010)
  • Author(s): Ohishi M, Takeya Y, Tatara Y, Yamamoto K, Onishi M, Maekawa Y, Kamide K,Rakugi H.
  • Journal Title: Hypertens Res. Volume: 33 Pages: 1150-1154
  • Peer Reviewed
• [Journal Article] The counterregulating role of ACE2 andACE2-mediated angiotensin 1-7 signaling against angiotensin II stimulation invascular cells. (2010)
  • Author(s): Hayashi N, Yamamoto K, Ohishi M, Tatara Y, Takeya Y, Shiota A, Oguro R,Iwamoto Y, Takeda M, Rakugi H.
  • Journal Title: Hypertens Res. Volume: 33 Pages: 1182-1185
  • Peer Reviewed
• [Journal Article] Comparison of strictand mild-blood pressure control in elderly hypertensive patients: a per-protocol analysis of JATOS. (2010)
  • Author(s): Rakugi H, Ogihara T, Goto Y, Ishii M; JATOS Study Group.
  • Journal Title: Hypertens Res. Volume: 33 Pages: 1124-1128
  • Peer Reviewed
• [Journal Article] Nifedipine inhibits vascular smooth muscle cell dedifferentiation via downregulation of Akt signaling. (2010)
  • Author(s): Kaimoto T, Yasuda O, Ohishi M, Mogi M, Takemura Y, Suhara T, Ogihara T, FukuoK, Rakugi H.
  • Journal Title: Hypertension. Volume: 56 Pages: 247-252
  • Peer Reviewed
• [Journal Article] Involvement of microsomal triglyceride transfer protein in nonalcoholic steatohepatitis in novel spontaneous mouse model. (2010)
  • Author(s): Shindo N, Fujisawa T, Sugimoto K, Nojima K, Oze-Fukai A, Yoshikawa Y, Wang X, Yasuda O, Ikegami H, Rakugi H.
  • Journal Title: J Hepatol. Volume: 52 Pages: 903-912
  • Peer Reviewed
• [Journal Article] Campylobacter fetus peritonitis in a patient with an unused embedded subcutaneous peritoneal catheter. (2010)
  • Author(s): Inoue K, Kitamura H, Nagasawa Y, Kawada N, Isaka Y, Rakugi H.
  • Journal Title: Perit Dial Int. Volume: 30 Pages: 253-254
  • Peer Reviewed
• [Journal Article] Loss of ACE2 accelerates time-dependent glomerular and tubulointerstitial damage in streptozotocin-induced diabetic mice. (2010)
  • Author(s): Shiota A, Yamamoto K, Ohishi M, Tatara Y, Ohnishi M, Maekawa Y, Iwamoto Y, Takeda M, Rakugi H.
  • Journal Title: Hypertens Res. Volume: 33 Pages: 298-307
  • Peer Reviewed
• [Journal Article] Microarray analysis of tonsils in immunoglobulin A nephropathy patients. (2010)
  • Author(s): Iio K, Nagasawa Y, Iwatani H, Yamamoto R, Horii A, Okuzaki D, Furumatsu Y, Inohara H, Nojima H, Imai E, Isaka Y, Rakugi H.
  • Journal Title: Biochem Biophys Res Commun Volume: 393 Pages: 565-570
  • Peer Reviewed
• [Journal Article] E-cadherin andclaudin-4 expression has circadian rhythm in adult rat kidney. (2010)
  • Author(s): Yamato M, Ito T, Iwatani H, Yamato M, Imai E, Rakugi H.
  • Journal Title: J Nephrol Volume: 23 Pages: 102-110
  • Peer Reviewed
• [Journal Article] Specialist care and improvedlong-term survival of dialysis patients. (2010)
  • Author(s): Furumatsu Y, Nagasawa Y, Yamamoto R, Iio K, Iwatani H, Matsui I, Takabatake Y, Kawada N, Shoji T, Imai E, Isaka Y, Rakugi H.
  • Journal Title: Nephrol Dial Transplant. Volume: 25 Pages: 1930-1935
  • Peer Reviewed
• [Journal Article] T elmisartan-induced inhibition of vascular cell proliferation beyond angiotensin receptor blockade and peroxisome proliferator-activated receptor-gamma activation. (2009)
  • Author(s): Yamamoto K, Ohishi M, Ho C, Kurtz TW, Rakugi H.
  • Journal Title: Hypertension. Volume: 54 Pages: 1353-1359
  • Peer Reviewed
• [Journal Article] Timp-3 deficiency impairs cognitive function in mice. (2009)
  • Author(s): Baba Y, Yasuda O, Takemura Y, Ishikawa Y, Ohishi M, Iwanami J, Mogi M, Doe N, Horiuchi M, Maeda N, Fukuo K, Rakugi H.
  • Journal Title: Lab Invest Volume: 89 Pages: 1340-1347
  • Peer Reviewed
• [Journal Article] The impact of diabetes mellituson vitamin D metabolism in predialysis patients. (2009)
  • Author(s): Tanaka H, Hamano T, Fujii N, Tomida K, Matsui I, Mikami S, Nagasawa Y, Ito T,Moriyama T, Horio M, Imai E, Isaka Y, Rakugi H.
  • Journal Title: Bone. Volume: 45 Pages: 949-955
  • Peer Reviewed
• [Journal Article] A candidate gene approach to genetic prognostic factors of IgA nephropathy--a result of Polymorphism REsearch to DIstinguish genetic factors Contributing To progression of IgA Nephropathy (PREDICT -IgAN). (2009)
  • Author(s): Yamamoto R, Nagasawa Y, Shoji T, Inoue K, Uehata T, Kaneko T, Okada T, Yamauchi A, Tsubakihara Y, Imai E, Isaka Y, Rakugi H.
  • Journal Title: Nephrol Dial Transplant Volume: 24 Pages: 3686-3694
  • Peer Reviewed
• [Journal Article] Klotho suppresses TNF-alpha-induced expression of adhesion molecules in the endothelium and attenuates NF-kappaB activation. (2009)
  • Author(s): Maekawa Y, Ishikawa K, Yasuda O, Oguro R, Hanasaki H, Kida I, Takemura Y,Ohishi M, Katsuya T, Rakugi H.
  • Journal Title: Endocrine. Volume: 35 Pages: 341-346
  • Peer Reviewed
• [Presentation] 降圧以上にぷらあすアルファの効果は本当にあるのか? (2012)
  • Author(s): 樂木宏実
  • Organizer: 第33回日本臨床薬理学会学術総会
  • Place of Presentation: 沖縄
  • Year and Date: 2012-11-03
• [Presentation] 健康長寿診療ハンドブックと高齢期の疾病・介護の予防 (2012)
  • Author(s): 樂木宏実
  • Organizer: 第19回日本未病システム学会
  • Place of Presentation: 金沢
  • Year and Date: 2012-10-28
• [Presentation] Effect of azilsartan on the circadian rhythm of blood pressure in Japanese essential hypertension (2012)
  • Author(s): Rakugi H
  • Organizer: Abstracts of the 24th Meeting of the Internal Society of Hypertension
  • Place of Presentation: Sydney
  • Year and Date: 2012-10-03
• [Presentation] Combination therapy in hypertension with CKD (2012)
  • Author(s): Rakugi H
  • Organizer: Abstracts of the 24th Meeting of the Internal Society of Hypertension
  • Place of Presentation: Sydney
  • Year and Date: 2012-10-02
• [Presentation] 日本 JSH2009 (2012)
  • Author(s): 樂木宏実
  • Organizer: 第35回日本高血圧学会総
  • Place of Presentation: 名古屋
  • Year and Date: 2012-09-22
• [Presentation] VALISH: The valsartan in elderly isolated systolic hypertension study (2012)
  • Author(s): 樂木宏実
  • Organizer: 第35回日本高血圧学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2012-09-21
• [Presentation] 高血圧制圧の戦略:新規降圧療法の開発 (2012)
  • Author(s): 樂木宏実
  • Organizer: 第35回日本高血圧学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2012-09-20
• [Presentation] 高齢者高血圧の血圧正常化の有用性と安全性:VALISH 研究サブ解析 (2012)
  • Author(s): 樂木宏実
  • Organizer: 第35回日本高血圧学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2012-09-20
• [Presentation] 実地医家の教育 (2012)
  • Author(s): 樂木宏実
  • Organizer: 第54回日本老年医学会学術集会・総会
  • Place of Presentation: 東京
  • Year and Date: 2012-06-30
• [Presentation] 高齢者と高血圧治療 (2012)
  • Author(s): 樂木宏実
  • Organizer: 第54回日本老年医学会学術集会・総会
  • Place of Presentation: 東京
  • Year and Date: 2012-06-29
• [Presentation] ハンドブックが目指すもの:編集者の立場から (2012)
  • Author(s): 樂木宏実
  • Organizer: 第54回日本老年医学会学術集会・総会
  • Place of Presentation: 東京
  • Year and Date: 2012-06-29
• [Presentation] 新規降圧薬の開発 (2012)
  • Author(s): 樂木宏実
  • Organizer: 第一回臨床高血圧フォーラム
  • Place of Presentation: 大阪
  • Year and Date: 2012-05-12
• [Presentation] 高血圧と血管老化 (2010)
  • Author(s): 樂木宏実
  • Organizer: 第18回日本血管生物医学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2010-12-01
• [Presentation] 老年医学の新しい展望 (2010)
  • Author(s): 樂木宏実
  • Organizer: 第21回老年医学会北陸地方会
  • Place of Presentation: 福井
  • Year and Date: 2010-11-13
• [Presentation] VALISH study から (2010)
  • Author(s): 樂木宏実
  • Organizer: 第33回日本高血圧学会総会
  • Place of Presentation: 福岡
  • Year and Date: 2010-10-15
• [Presentation] VALISH からのレッスン (2010)
  • Author(s): 樂木宏実
  • Organizer: 第33回日本高血圧学会総会
  • Place of Presentation: 福岡
  • Year and Date: 2010-10-15
• [Presentation] ガイドライン改訂の課題 (2010)
  • Author(s): 樂木宏実
  • Organizer: 第33回日本高血圧学会総会
  • Place of Presentation: 福岡
  • Year and Date: 2010-10-15
• [Presentation] 本態性高血圧-成因・診断・治療- (2010)
  • Author(s): 樂木宏実
  • Organizer: 老年医学会 北陸地方会
  • Place of Presentation: 福井
  • Year and Date: 2010-10-13
• [Presentation] Optimal Target Blood Pressure for Elderly Hypertensive Patients (2010)
  • Author(s): Rakugi H
  • Organizer: The 23rd scientific meeting of the International Society of Hypertension
  • Place of Presentation: Vancouver
  • Year and Date: 2010-09-27
• [Presentation] 高齢者高血圧の治療指針 (2010)
  • Author(s): 樂木宏実
  • Organizer: 第52回日本老年医学会学術集会
  • Place of Presentation: 神戸
  • Year and Date: 2010-06-24
• [Presentation] 糖尿病患者の高血圧治療と糖尿病発症予防の高血圧治療 (2010)
  • Author(s): 樂木宏実
  • Organizer: 第53回日本糖尿病学会年次学術集会
  • Place of Presentation: 岡山
  • Year and Date: 2010-05-28
• [Book] 高齢者の降圧目標と薬剤選択 (2012)
  • Author(s): 樂木宏実
  • Total Pages: 160-163
  • Publisher: 日本医事神新報社
• [Book] 高血圧 (2012)
  • Author(s): 樂木宏実
  • Total Pages: 169-170
  • Publisher: 西村書店
• [Book] アンジオテンシン変換酵素(ACE)、内分泌性高血圧診療マニュアル (2010)
  • Author(s): 樂木宏実
  • Total Pages: 44-49
• [Book] 高血圧治療ガイドラインと内分泌性高血圧、内分泌性高血圧診療マニュアル (2010)
  • Author(s): 樂木宏実
  • Total Pages: 5-6
• [Book] 低カリウムを伴う高血圧の鑑別診断、内分泌性高血圧診療マニュアル (2010)
  • Author(s): 樂木宏実
  • Total Pages: 78-79
• [Remarks]
  • URL: http://www.med.osaka-u.ac.jp/pub/geriat/www/index_g.html