Molecular Mechanism of Intracellular Vacuolation in Acute Pancreatitis

急性胰腺炎细胞内空泡形成的分子机制

• 批准号: 12670465
• 负责人: OHNISHI Hirohide
• 金额: $ 2.5万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670465/
• 关键词: Acute Pancreatitis; Vesicle Traffic; Kinesin; Dynamin; Vacuolation; Exocrine Pancreas; 空胞; 小胞輸送

The molecular pathological mechanism of acute pancreatitis is still unclear. However, it is widely believed that the intracellular pathological vacuolation formed by abnormal fusion of zymogen granules and lysosomes is the first event in developing acute pancreatitis. To elucidate the molecular mechanism of the vacuoltaion, we first studied on the molecular mechanism of zymogen granule trafficking in pancreatic acinar cells. We have demonstrated that both dynamin and kinesin , mechanocehmical enzymes, are localized on zymogen granules and involved in zymogen granule trafficking. Using in vitro vacuolation system, we also revealed dynamin is involved in pathological vacuolation and that dominant negative dynamin could inhibit pathological vacuolation. These data indicate that intracellular vesicle traffic system is involved in pathological vacuolation.

急性胰腺炎的分子病理机制尚不清楚。然而，目前普遍认为，由酶原颗粒与溶酶体异常融合形成的细胞内病理空泡化是急性胰腺炎发展的第一个事件。为了阐明空泡形成的分子机制，我们首先研究了胰腺腺泡细胞酶原颗粒运输的分子机制。我们已经证明，动力蛋白和驱动蛋白，机械酶，是本地化的酶原颗粒和参与酶原颗粒运输。利用体外空泡形成系统，我们还发现发动蛋白参与了病理性空泡形成，显性负性发动蛋白可抑制病理性空泡形成。这些数据表明，细胞内囊泡运输系统参与了病理性空泡化。

项目成果

Hirohide Ohnishi: "Novel molecular mechanism of the regulation and signaling of pancreatic acinar secretion through zymogen granule proteins"Tan to Sui. 21(3). 227-234 (2000)

Hirohide Ohnishi：“通过酶原颗粒蛋白调节胰腺腺泡分泌的新分子机制”Tan to Sui。

Suzuki J,Ohnishi H,Shibata H,Wada A,Hirayama T,Iiri T,Ueda N,Kanamaru C,Tsuchida T,Mashima H,Yasuda H,Fujita T.: "Dynamin is involved in the vacuolation induced by Helicobacter pylori vacuolating cytotoxin (VacA) in human epithelial cells."J.Clin.Invest..

Suzuki J、Ohnishi H、Shibata H、Wada A、Hirayama T、Iiri T、Ueda N、Kanamaru C、Tsuchida T、Mashima H、Yasuda H、Fujita T.：“Dynamin 参与幽门螺杆菌空泡细胞毒素诱导的空泡形成

Chiho Kanamaru: "Smad7 Is Induced by Norepinephrine and Protects Rat Hepatocytes from Activin A-induced Growth Inhibition"Journal of Biological Chemistry. 276. 45636-45641 (2001)

Chiho Kanamaru：“Smad7 由去甲肾上腺素诱导并保护大鼠肝细胞免受激活素 A 诱导的生长抑制”生物化学杂志。

大西 洋英: "膵外分泌における細胞内刺激伝達系"胆と膵. 21(3). 227-234 (2000)

Hiroshi Onishi：“外分泌胰腺的细胞内刺激传递系统”Bile and Pancreas 21(3) (2000)。

Junko Suzuki et al.: "Dynamin is involved in human epithelial cell vacuolation caused by the helicobacter pylori-produced cytotoxin VacA"Journal of Clinical Investigation. 107(3). 363-370 (2001)

Junko Suzuki 等人：“Dynamin 参与由幽门螺杆菌产生的细胞毒素 VacA 引起的人上皮细胞空泡形成”《临床研究杂志》。