臓器障害進行過程における遺伝子及びエネルギ－獲得機能の変化

2014 Fiscal Year Research-status 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 / 臓器障害 / アポト－シス / 酸化ストレス

Outline of Annual Research Achievements

糖尿病に限らずほとんど全ての疾患に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。糖尿病モデル動物として、Zucker・ZDF・SDT・ob/obなどの遺伝的ラット・マウスやストレプトゾトシン誘発モデル等がある。　糖尿病モデル動物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した。その結果、糖尿病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、糖尿病合併症治療に効果的であると考えられた。　今後、さらなる研究により安全かつ効果的に糖尿病合併症の治療が行われることを切望する。

Current Status of Research Progress

1: Research has progressed more than it was originally planned.

Reason

研究成果が欧米の学術雑誌に掲載された。

Strategy for Future Research Activity

このまま研究を継続する。

Research Products

• [Journal Article] Schisandrin B Prevents Doxorubicin Induced Cardiac Dysfunction by Modulation of DNA Damage, Oxidative Stress and Inflammation through Inhibition of MAPK/p53 Signaling. (2015)
  • Author(s): Rajarajan A. Thandavarayan, Vijayasree V. Giridharan, Somasundaram Arumugam, Kenji Suzuki, Kam Ming Ko, Prasanna Krishnamurthy, Kenichi Watanabe, Tetsuya Konishi.
  • Journal Title: PLOS ONE Volume: 10 Pages: 1-18
  • DOI: 10.1371/journal.pone. 0119214
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Myocardial 14-3-3η protein protects against mitochondria mediated apoptosis (2015)
  • Author(s): Remya Sreedhar, Somasundaram Arumugam, Rajarajan A. Thandavarayan, Vijayasree V. Giridharan, Vengadeshprabhu Karuppagounder, Vigneshwaran Pitchaimani, Rejina Afrin, Shizuka Miyashita, Mayumi Nomoto, Meilei Harima, Narasimman Gurusamy, Kenji Suzuki, Kenichi Watanabe.
  • Journal Title: Cellular Signalling. Volume: ２７ Pages: ７７０-７７６
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Prevention of DSS induced acute colitis by Petit Vert, a newly developed function improved vegetable, in mice (2014)
  • Author(s): Somasundaram A, Rajarajan A. T, Vigneshwaran P,Vengadeshprabhu K, Harima M, Nishizawa Y, Sasaki K, Suzuki K, Konishi T, Watanabe K.
  • Journal Title: Pharma Nutrition Volume: ２ Pages: １２９-１３４
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Resveratrol attenuates HMGB1 signaling and inflammation in house dust mite-induced atopic dermatitis in mice. (2014)
  • Author(s): Vengadeshprabhu K, Somasundaram A, Rajarajan A T, Vigneshwaran P, Remya S, Rejina A, Harima M, Suzuki H, Nomoto M, Miyashita S, Suzuki K, Watanabe K.
  • Journal Title: Int Imunopharmacol Volume: ２３ Pages: ６１７-６２３
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Comparative evaluation of torasemide and furosemide on rats with streptozotocin-induced diabetic nephropathy. (2014)
  • Author(s): Somasundaram A, Remya S, Vengadesh K, Rajarajan A. T, Vijayasree V, Vigneshwaran P, Rejina A, Harima M, Suzuki K, , K Watanabe.
  • Journal Title: Experimental and Molecular Pathology Volume: ９７ Pages: １３７-１４３
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Fasting mediated increase in p-BADser155 and p-AKTser473 in the prefrontal cortex of mice. (2014)
  • Author(s): Vigneshwaran Pitchaimani, Somasundaram Arumugam, Rajarajan Amirthalingam, Thandavarayan, Vengadeshprabhu Karuppagounder, Remya Sreedhar, Rejina Afrin, Meilei Harima, Hiroshi Suzuki, Shizuka Miyashita, Mayumi Nomoto, Hirohito Sone, Kenji Suzuki, Kenichi Watanabe.
  • Journal Title: Neuroscience Letters. Volume: 579 Pages: 134-139
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Glucose transporter expression in cortex and hippocampus of fasting, moderate and severe hypoglycemia of mice. (2014)
  • Author(s): Vigneshwaran Pitchaimani, Somasundaran Arumugam, Rajarajan A Thandavarayan, Vengadeshprabhu Karuppa Gounder, Remya Sreeedhar, Meilei Harima, Hiroshi Suzuki, Shizuka Miyashita, Mayumi Nomoto, Kenji Suzuki, Kenichi Watanabe
  • Organizer: DIABETIC AND METABOLIC SYNDROME
  • Place of Presentation: Haryana, India
  • Year and Date: 2014-11-24 – 2014-11-29
• [Presentation] Dominant Negative 14-3-3 Protein Exacerbates Cardiac Dysfunction by Suppressing Cardiac Regeneration After Coronary Artery ligation in mice. (2014)
  • Author(s): Rajarajan Amirthalingam Thandavarayan , Somasundaram Arumugam, Vigneshwaran Pitchaimani, Vengadeshprabhu Karuppa Gounder, Vijayasree Vayalanellore, Remya Sreedhar, Meilei Harima, Darukeshwara Joladarashi, Kenji Suzuki, Kenichi Watanabe
  • Organizer: American heart Association
  • Place of Presentation: Chicago. USA
  • Year and Date: 2014-11-15 – 2014-11-19