Initial event of protein degeneration during the gastric mucosal injury

• Project/Area Number: 19590712
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Juntendo University
• Principal Investigator: OTAKA Michiro Juntendo University, 医学部, 准教授 (30250872)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2007: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 胃粘膜傷害 / 胃潰瘍 / 分子シャペロン / ポストゲノム / 熱ショック蛋白質 / HSP結合蛋白質 / 消化性潰瘍 / HSP / 胃粘膜

Research Abstract

ストレス誘発性胃潰瘍では胃粘膜傷害の生ずる前より胃粘膜上皮細胞内の蛋白質変性は始まっており、HSP70アフィニティークロマトグラフィーに結合する200-kDaおよび45-kDaの2種類の蛋白質の高次構造の変化が、ストレスによる胃粘膜傷害のinitial eventであると考えられた。また、そのアミノ酸配列よりこれらの蛋白質はミオシン重鎖およびアクチンであることが明らかになった。これまで、胃粘膜傷害のinitiatorやinitial eventは全く不明であったが、約十数秒の間に変性した蛋白質に結合し、高次構造を正常化するHSPの性質を利用することにより、潰瘍治療の標的と成り得る分子を同定できた。この成果は将来の分子医学的あるいはポストゲノム時代の潰瘍治療の開発に寄与するものと考えられた。

Research Products

• [Journal Article] Specific induction of a 72-kDa heat shock protein protects esophageal mucosa from reflux esophagitis (2009)
  • Author(s): Izumi Y, Otaka M, Takahashi T, Takada M, Shimada Y, Asaoka D, Nagahara A, Itoh H, Watanabe S
  • Journal Title: Life Sci 84(15-16) Pages: 517-522
• [Journal Article] Target molecules of molecular chaperon (HSP70 family) in injured gastric mucosa in vivo (2009)
  • Author(s): Otaka M, Odashima M, Izumi Y, Nagahara A, Osada T, Sakamoto N, Takada M, Takahashi T, Shimada Y, Tamaki K, Asaoka D, Itoh H, Watanabe S
  • Journal Title: Life Sci 84(19-20) Pages: 664-667
• [Journal Article] Heat shock protein 70 over-expressing gastric epithelial cells are resistant to indomethacin-induced apoptosis (2009)
  • Author(s): Hirata I, Naito Y, Handa O, Hayashi N, Mizushima K, Adachi S, Omatsu T, Okayama T, Kishimoto E, Ichikawa H, Takagi T, Kokura S, Otaka M, Yoshikawa T
  • Journal Title: Digestion 79(4) Pages: 243-250
• [Journal Article] Attenuation of gastric mucosal inflammation induced by indomethacin through activation of the A2A adenosine receptor in rats (2009)
  • Author(s): Koizumi S, Odashima M. Otaka M, Jin M, Linden J, Watanabe S, Ohnishi H
  • Journal Title: J Gastroenterol 44(5) Pages: 419-425
• [Journal Article] Expression and function of stress (heat shock) proteins in gastrointestinal tract (2009)
  • Author(s): Otaka M, Watanabe S
  • Journal Title: Int J Heperthermia (in press)
• [Journal Article] 消化管上皮細胞のHSP発現機構の分子生物学 (2009)
  • Author(s): 大高道郎、和泉裕子、渡辺純夫
  • Journal Title: G. I. Research 17 Pages: 154-158
• [Journal Article] Target molecules of molecular chaperon (HSP70 family) in injured gastric mucosa in vivo. (2009)
  • Author(s): Otaka M, et al.
  • Journal Title: Life Sci Pages: 664-667
  • Peer Reviewed
• [Journal Article] Cisplatin differently affects amino terminal and carboxyl terminal domains of HSP90 (2008)
  • Author(s): Ishida R, Takaoka Y, Yamamotoa S, Miyazaki T, Otaka M, Watanabe S, Komatsuda A, Wakui H, Sawada K, Kubota H, Itoh H
  • Journal Title: FEBS. Lett 582(28) Pages: 3879-3883
• [Journal Article] 消化器疾患における亜鉛の重要性-亜鉛による消化管粘膜保護作用を中心に- (2008)
  • Author(s): 大高道郎, 渡辺純夫
  • Journal Title: G. I. Research 16 Pages: 164-169
• [Journal Article] 分子シャペロンと消化器疾患 (2008)
  • Author(s): 伊藤英晃, 大高道郎, 渡辺純夫
  • Journal Title: 分子細胞治療 7 Pages: 36-42
• [Journal Article] The induction mechanism of the molecular chaperone HSP70 in the gastric mucosa by Geranylgeranylacetone (HSP-inducer) (2007)
  • Author(s): Otaka M, Yamamoto S, Ogasawara K, Takaoka Y, Noguchi S, Miyazaki T, NakaiA, Odashima M, Matsuhashi T, Watanabe S, Itoh H
  • Journal Title: Biochem. Biophys. Res. Commun. 353(2) Pages: 399-404
• [Journal Article] Mitigation of stress-induced gastric mucosal lesion by specific type IV phosphodiesterase inhibitor (2007)
  • Author(s): Kato S, Otaka M (Equalcontribution to the firstauthor), Odashima M, Sato T, Jin M, Matsuhashi T, Konishi N, Watanabe S
  • Journal Title: Dig. Dis. Sci. 52(3) Pages: 711-716
• [Journal Article] Attenuation of gastric mucosal inflammation induced by aspirin through inhibition of the selective type III phospshodiesterase in rats (2007)
  • Author(s): Odashima M, Otaka M (Equalcontribution to the firstauthor), Ohba R, Jin M, Horikawa Y, Matsuhashi T, Hatakeyama N, Oyake J, Watanabe S
  • Journal Title: Dig. Dis. Sci. 52 Pages: 1355-1359
• [Journal Article] Protective effect of novel rice extract against ethanol-induced gastric mucosal injury in rat (2007)
  • Author(s): Matsuhashi T, Otaka M, Odashima M, Jin M, Komatsu K, Wada I, Horikawa Y, Ohba R, Oyake J, Hatakeyama N, Watanabe S
  • Journal Title: Dig Dis Sci 52(2) Pages: 434-441
• [Journal Article] Effect of alcohol consumption on leptin level in serum,adipose tissue and gastric mucosa (2007)
  • Author(s): Otaka M, Konishi N, Odashima M, Jin M, Wada I, Matsuhashi T, Ohba R, Watanabe S
  • Journal Title: Dig. Dis. Sci 52(11) Pages: 3066-3069
• [Journal Article] MEK-activationsuppresses CPT11-induced apoptosis in rat intestinal epithelial cells through COX-2- dependent mechanism (2007)
  • Author(s): Horikawa Y, Otaka M, Komatsu K, Jin M, Odashima M, Wada I, Matsuhashi T, Ohba R, Oyake J, Hatakeyama N, DuBois R, Watanabe S
  • Journal Title: Dig. Dis. Sci 52(10) Pages: 2757-2765
• [Journal Article] Mechanical strain stress suppresses expression of HSP70 and wound restoration in the gastric mucosal cells (2007)
  • Author(s): Odashima M, Otaka M (Equalcontribution to the firstauthor), Matsuhashi T, Jin M, Horikawa Y, Ohba R, Itoh H, Watanabe S
  • Journal Title: Dig. Dis. Sci 52(11) Pages: 3087-3091
• [Journal Article] 消化管器疾患におけるストレス蛋白質(分子シャペロン)の発現とその意義-分子シャペロン誘導療法への展望も含めて- (2007)
  • Author(s): 大高道郎
  • Journal Title: 日本ストレス学会誌 21 Pages: 141-151
• [Journal Article] 高齢者消化器疾患における亜鉛の重要性-亜鉛による消化管粘膜保護作用も含めて- (2007)
  • Author(s): 大高道郎, 小田嶋傑, 渡辺大亮, 渡辺純夫
  • Journal Title: 老年消化器病 19 Pages: 73-78
• [Journal Article] 消化器疾患における亜鉛の有用性-胃、大腸粘膜におけるHSP誘導作用を中心に- (2007)
  • Author(s): 大高道郎, 小田嶋傑, 渡辺大亮, 三上健一郎, 渡辺純夫
  • Journal Title: Biomed. Res. Trace Elements 18 Pages: 15-19
  • NAID: 10018910824
• [Journal Article] The induction mechanism of the molecular chaperone HSP70 in the gastric mucosa by Geranylgeranylacetone(HSP-inducer) (2007)
  • Author(s): Otaka M, et. al.
  • Journal Title: Biochem Biophys Res Commun 353 Pages: 399-404
  • Peer Reviewed
• [Journal Article] Mechanical strain stress suppresses expression of HPS70 and wound restoration in the gastric mucosal cells (2007)
  • Author(s): Odashima M, Otaka M, et. al.
  • Journal Title: Dig Dis Sci 52 Pages: 3087-3091
  • Peer Reviewed
• [Journal Article] Effect of Alcohol Consumption on Leptin Level in Serum, Adipose Tissue,and Gastric Mucosa (2007)
  • Author(s): Otaka M, et. al.
  • Journal Title: Dig Dis Sci 52 Pages: 3066-3069
  • Peer Reviewed
• [Presentation] Contribution of heat shock proteins expression to gender difference in development of stress-induced gastric mucosal injury in rats (2009)
  • Author(s): Takahashi, T., Otaka, M., Izumi, Y., Takada, M., Shimada, Y., Itoh, H. and Watanabe, S.
  • Organizer: 110th the American Gastroenterological Association
  • Place of Presentation: Chicago
• [Presentation] Specific induction of a 72-kDa heat shock protein protects esophageal mucosa from reflux esophagitis (2009)
  • Author(s): Izumi, Y., Otaka, M., Takahashi, T., Takada, M., Shimada, Y., Asaoka, D., Nagahara, A., Itoh, H. and Watanabe, S.
  • Organizer: 110th the American Gastroenterological Association
  • Place of Presentation: Chicago
• [Presentation] Investigation of laryngo-trancheal lesion in a rat chronic acid reflux esophagitis (2009)
  • Author(s): Oguro, M., Nagahara, A., Asaoka, D., Nakayama, H., Izumi, Y., Otaka, M. and Watanabe, S.
  • Organizer: 110th the American Gastroenterological Association
  • Place of Presentation: Chicago
• [Presentation] Over-expression of a 70-kDa heat shock protein enhances cytoprotective function against hydrogen peroxide or NSAIDs-induced smallintestinal epithelial cells in jury (2009)
  • Author(s): Takada, M., Otaka, M., Takahashi, T., Izumi, Y., Shimada, Y., Itoh, H. and Watanabe, S.
  • Organizer: 110th the American Gastroenterological Association
  • Place of Presentation: Chicago
• [Presentation] Target molecules of molecular chaperone (HSP70) in injured gastric mucosal cells are cytoskeletal myosin (2008)
  • Author(s): Izumi, Y., Otaka, M., Nagahara, A., Asaoka, D., Sakamoto, N., Osada, T., Kawabe, M., Ohkusa, T., Odashima, M., Itoh, H. and Watanabe, S.
  • Organizer: 109th the American Gastroenterological Association
  • Place of Presentation: San Diego
• [Presentation] Target molecules of molecular chaperon (HSP70 family) in injured gastric mucosa in vivo. (2008)
  • Author(s): Izumi Y, Otaka M, et al.
  • Organizer: 米国消化器病学会(AGA)
  • Place of Presentation: サンディエゴ(米国)
• [Presentation] 圧迫骨折、肥満と食道裂孔ヘルニア、逆流食道炎の関連-高齢者での検討 (2007)
  • Author(s): 吉村 美保, 他
  • Organizer: 第10回日本高齢消化器病学会
  • Place of Presentation: 北海道
• [Book] がんの温熱免疫療法 (2008)
  • Author(s): 大高道郎
  • Publisher: 診断と治療社, 東京