Change of pathways in organ damage

2016 Fiscal Year Annual Research Report

• Project/Area Number: 26460239
• Research Institution: Nigata University of Phermacy and Applied Life Sciences
• Principal Investigator: 渡邊 賢一 新潟薬科大学, 薬学部, 教授 (70175090)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 糖尿病 / 潰瘍性大腸炎 / アトピー皮膚炎 / 酸化ストレス / 心不全 / モデル動物

Outline of Annual Research Achievements

「背景」臓器障害特に糖尿病性腎症などでは酸化ストレスが関係することが明らかになりつつある。　一方、小胞体ストレスおよび小胞体を介するアポトーシスも注目されつつある。　小胞体はタンパクの構築、脂質やコレステロールの代謝を行う重要な細胞内器官である。　小胞体ストレスが蓄積すると、細胞内に折りたたまれない蛋白が増加・活性化しGRP78が活性化される。　GRP78はさらにIRE1・PERK・ATF6を活性化する。　小胞体ストレスが長引けば、CHOP経路を介して更に下流のアポト－シス経路を刺激する。「目的」糖尿病モデル動物や潰瘍性大腸炎モデル動物を用い各組織における酸化ストレス・小胞体ストレスの関与について検討する。「方法」糖尿病・潰瘍性大腸炎・アトピー皮膚炎モデル動物を用い各組織における酸化ストレス・小胞体ストレスをウエスタンブロット・免疫染色などで検討した。「研究成果」障害臓器の各組織では酸化ストレス・小胞体ストレス・アポトーシスが亢進していた。　酸化ストレスや小胞体ストレスを抑制することは、糖尿病合併症治療等に効果的であると考えられた。

Research Products

• [Journal Article] Comparative effects of torasemide and furosemide on gap junction proteins and cardiac fibrosis in a rat model of dilated cardiomyopathy. (2017)
  • Author(s): Watanabe K, Sreedhar R, Thandavarayan RA, Karuppagounder V, Giridharan VV, Antony S, Harima M, Nakamura M, Suzuki K, Suzuki H, Sone H, Arumugam S.
  • Journal Title: Biofactors. Volume: 43 Pages: 187-194
  • DOI: 10.1002/biof.1332
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] The senescence accelerated mouse prone 8 (SAMP8): A novel murine model for cardiac aging (2017)
  • Author(s): Karuppagounder V, Arumugam S, Babu SS, Palaniyandi SS, Watanabe K, Cooke JP, Thandavarayan RA.
  • Journal Title: Ageing Res Rev. Volume: 35 Pages: 291-296
  • DOI: 10.1016/j.arr.2016.10.006.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Curcumin ameliorates liver damage and progression of NASH in NASH-HCC mouse model possibly by modulating HMGB1-NF-κB translocation. (2017)
  • Author(s): Afrin R, Arumugam S, Rahman A, Wahed MI, Karuppagounder V, Harima M, Suzuki H, Miyashita S, Suzuki K, Yoneyama H, Ueno K, Watanabe K.
  • Journal Title: Int Immunopharmacol Volume: 44 Pages: 174-182
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Le Carbone, a charcoal supplement, modulates DSS-induced acute colitis in mice through activation of AMPKα and downregulation of STAT3 and caspase 3 dependent apoptotic pathways. (2017)
  • Author(s): Afrin MR, Arumugam S, Rahman MA, Karuppagounder V, Sreedhar R, Harima M, Suzuki H, Nakamura T, Miyashita S, Suzuki K, Ueno K, Watanabe K.
  • Journal Title: Int Immunopharmacol. Volume: 43 Pages: 70-78
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Tiny molecule, big power: Multi-target approach for curcumin in diabetic cardiomyopathy. (2017)
  • Author(s): Karuppagounder V, Arumugam S, Giridharan VV, Sreedhar R, Bose RJ, Vanama J, Palaniyandi SS, Konishi T, Watanabe K,
  • Journal Title: Nutrition Volume: 34 Pages: 47-54
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Curcumin alleviates renal dysfunction and suppresses inflammation by shifting from M1 to M2 macrophage polarization in daunorubicin induced nephrotoxicity in rats. (2016)
  • Author(s): Karuppagounder V, Arumugam S, Thandavarayan RA, Sreedhar R, Giridharan VV, Afrin R, Harima M, Miyashita S, Hara M, Suzuki K, Nakamura M, Ueno K, Watanabe K.
  • Journal Title: Cytokine. Volume: 84 Pages: 1-9
  • DOI: 10.1016/j.cyto.2016.05.001
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Pivotal Role of Carbohydrate Sulfotransferase 15 in Fibrosis and Mucosal Healing in Mouse Colitis. (2016)
  • Author(s): Suzuki K, Arumugam S, Yokoyama J, Kawauchi Y, Honda Y, Sato H, Aoyagi Y, Terai S, Okazaki K, Suzuki Y, Mizumoto S, Sugahara K, Atreya R, Neurath MF, Watanabe K, Hashiguchi T, Yoneyama H, Asakura H.
  • Journal Title: PLoS One Volume: 13 Pages: -
  • DOI: e0158967
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Fasting time duration modulates the onset of insulin-induced hypoglycemic seizures in mice. (2016)
  • Author(s): Pitchaimani V, Arumugam S, Thandavarayan RA, Karuppagounder V, Afrin MR, Sreedhar R, Harima M, Suzuki H, Miyashita S, Nakamura T, Suzuki K, Nakamura M, Ueno K, Watanabe K.
  • Journal Title: Epilepsy Res Volume: 125 Pages: 47-51
  • DOI: 10.1016/j.eplepsyres.2016.06.009
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Targeting fatty acid metabolism in heart failure: is it a suitable therapeutic approach? (2016)
  • Author(s): Arumugam S, Sreedhar R, Thandavarayan RA, Karuppagounder V, Watanabe K.
  • Journal Title: Drug Discov Today Volume: 21 Pages: 1003-1008
  • DOI: 10.1016/j.drudis.2016.02.010
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Curcumin as a therapeutic agent in the chemoprevention of inflammatory bowel disease. (2016)
  • Author(s): Sreedhar R, Arumugam S, Thandavarayan RA, Karuppagounder V, Watanabe K.
  • Journal Title: Drug Discov Today Volume: 21 Pages: 843-849
  • DOI: 10.1016/j.drudis.2016.03.007
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Molecular targets of quercetin with anti-inflammatory properties in atopic dermatitis. (2016)
  • Author(s): Karuppagounder V, Arumugam S, Thandavarayan RA, Sreedhar R, Giridharan VV, Watanabe K.
  • Journal Title: Drug Discov Today Volume: 21 Pages: 632-639
  • DOI: 10.1016/j.drudis.2016.02.011
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Modulation of Macrophage Polarization and HMGB1-TLR2/TLR4 Cascade Plays a Crucial Role for Cardiac Remodeling in Senescence-Accelerated Prone Mice. (2016)
  • Author(s): Karuppagounder V, Giridharan VV, Arumugam S, Sreedhar R, Palaniyandi SS, Krishnamurthy P, Quevedo J, Watanabe K, Konishi T, Thandavarayan RA.
  • Journal Title: PLoS One. Volume: 12 Pages: -
  • DOI: e0152922.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Angiotensin receptor blockers: Focus on cardiac and renal injury. (2016)
  • Author(s): Arumugam S, Sreedhar R, Thandavarayan RA, Karuppagounder V, Krishnamurthy P, Suzuki K, Nakamura M, Watanabe K.
  • Journal Title: Trends Cardiovasc Med. Volume: 26 Pages: 221-228
  • DOI: 10.1016/j.tcm.2015.06.004
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Role of MAPK-mediated endoplasmic reticulum stress signaling in the heart during aging in senescence-accelerated prone mice. (2016)
  • Author(s): Sreedhar R, Giridharan VV, Arumugam S, Karuppagounder V, Palaniyandi SS, Krishnamurthy P, Quevedo J, Watanabe K, Konishi T, Thandavarayan RA.
  • Journal Title: Biofactors. Volume: 42 Pages: 368-375
  • DOI: 10.1002/biof.1280
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Hypothalamic glucagon signaling in fasting hypoglycemia. (2016)
  • Author(s): Pitchaimani V, Arumugam S, Thandavarayan RA, Karuppagounder V, Afrin MR, Sreedhar R, Harima M, Suzuki H, Miyashita S, Suzuki K, Nakamura M, Ueno K, Watanabe K.
  • Journal Title: Life Sci. Volume: 153 Pages: 118-123
  • DOI: 10.1002/biof.1280
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Naringenin ameliorates skin inflammation and accelerates phenotypic reprogramming from M1 to M2 macrophage polarization in atopic dermatitis NC/Nga mouse model. (2016)
  • Author(s): Karuppagounder V, Arumugam S, Thandavarayan RA, Sreedhar R, Giridharan VV, Pitchaimani V, Afrin R, Harima M, Krishnamurthy P, Suzuki K, Nakamura M, Ueno K, Watanabe K.
  • Journal Title: Exp Dermatol. Volume: 25 Pages: 404-407
  • DOI: 10.1111/exd.12962
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Attenuation of Endoplasmic Reticulum Stress-Mediated Liver Damage by Mulberry Leaf Diet in Streptozotocin-Induced Diabetic Rats. (2016)
  • Author(s): .Afrin R, Arumugam S, Wahed MI, Pitchaimani V, Karuppagounder V, Sreedhar R, Harima M, Suzuki H, Miyashita S, Nakamura T, Suzuki K, Nakamura M, Ueno K, Watanabe K.
  • Journal Title: Am J Chin Med. Volume: 44 Pages: 87-101
  • DOI: 10.1142/S0192415X16500063
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Depletion of cardiac 14-3-3η protein adversely influences pathologic cardiac remodeling during myocardial infarction after coronary artery ligation in mice. (2016)
  • Author(s): Sreedhar R, Arumugam S, Thandavarayan RA, Giridharan VV, Karuppagounder V, Pitchaimani V, Afrin R, Harima M, Nakamura M, Suzuki K, Gurusamy N, Krishnamurthy P, Watanabe K.
  • Journal Title: Int J Cardiol. Volume: 202 Pages: 146-153
  • DOI: 10.1016/j.ijcard.2015.08.142
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant