IDENTIFICATION OF NITRIC OXIDE RELATED PROTEIN EXPRESSED IN TRANSACTIVATED ITO CELLS

反式激活 ITO 细胞中表达的一氧化氮相关蛋白的鉴定

• 批准号: 11670511
• 负责人: SAIBARA Toshiji
• 金额: $ 2.18万
• 依托单位: KOCHI MEDICAL SCHOOL
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670511/
• 关键词: ITO CELLS; LIVER; RAT; STELLATE CELLS; MYOFIBROBLAST; NITRIC OXIDE; rat; myofibroblast; nitric oxide; non-alcoholic steatohepatitis; NASH

Ito cells have a key role in regulating hepatic sinusoidal blood flow, because they contract in response to endothelin-1 and produce nitric oxide to dilate sinusoids. Progress in purification of Ito cells enabled us to obtain highly-purified cells and we investigate this process precisely through arginine transport and nitric oxide production in Ito cells. In this study, we developed monoclonal antibody for purifying protein transiently expressed in transformed Ito cells during the process of iNOS mediated nitric oxide production and partial amino acid sequence revealed it as unknown proteins. We need further investigation to recognize the role of these proteins in Ito cells during iNOS induction.Development of liver fibrosis is a life-threatening complications in chronic liver diseases. Oral administration of arginine, the substrate of nitric oxide, may be a promising way of an increase in sinusoidal blood flow in chronic liver diseases. A new insight into the iNOS related proteins expressed in Ito cells may provide an important information for improving hepatic blood flow.

Ito 细胞在调节肝窦血流中发挥着关键作用，因为它们响应内皮素-1 而收缩并产生一氧化氮来扩张肝窦。伊藤细胞纯化方面的进展使我们能够获得高度纯化的细胞，并且我们通过伊藤细胞中精氨酸的转运和一氧化氮的产生来精确地研究这一过程。在本研究中，我们开发了单克隆抗体，用于纯化在 iNOS 介导的一氧化氮产生过程中转化的 Ito 细胞中瞬时表达的蛋白质，部分氨基酸序列显示其为未知蛋白质。我们需要进一步研究以认识这些蛋白质在 iNOS 诱导过程中在 Ito 细胞中的作用。肝纤维化的发展是慢性肝病中危及生命的并发症。口服精氨酸（一氧化氮的底物）可能是增加慢性肝病患者肝窦血流量的一种有前途的方法。对 Ito 细胞中表达的 iNOS 相关蛋白的新认识可能为改善肝血流量提供重要信息。

项目成果

T.Tohyama, et al.: "Inhibitory effect of cathepsin B inhibitor CA074 on mouse anti-rat mixed lymphocyte reaction : novel immunosuppressive strategy for indirect xenoantigen recognition."Transplant P. 32. 944-945 (2000)

T.Tohyama 等人：“组织蛋白酶 B 抑制剂 CA074 对小鼠抗大鼠混合淋巴细胞反应的抑制作用：间接异种抗原识别的新型免疫抑制策略。”移植 P. 32. 944-945 (2000)

Y.Nemoto, et al.: "Altered constitutive expression of fatty acid-metabolizing enzymes in aromatase-deficient (ArKO) mice."J Clin Invest. 105. 1819-1825 (2000)

Y.Nemoto 等人：“芳香酶缺陷 (ArKO) 小鼠中脂肪酸代谢酶的组成型表达发生改变。”J Clin Invest。

Y.Murata, et al.: "Unrecognized hepatic steatosis and non-alcoholic steatohepatitis in adjuvant tamoxifen for breast cancer patients."Oncol Rep. 7. 1299-1304 (2000)

Y.Murata 等人：“乳腺癌患者辅助他莫昔芬中未识别的肝脂肪变性和非酒精性脂肪性肝炎。”Oncol Rep. 7. 1299-1304 (2000)

Y.Murata, et al.: "Unrecognized hepatic steatosis and non-alcoholic steatohepatitis in adjuvant tamoxifen for breast cancer patients."Oncology Reports. 7. 1299-1304 (2000)

Y.Murata 等人：“乳腺癌患者辅助他莫昔芬中未识别的肝脏脂肪变性和非酒精性脂肪性肝炎。”肿瘤学报告。

T.Saibara, et al.: "Non-alcoholic steatohepatitis."Lancet. 354. 1299-1300 (1999)

T.Saibara 等人：“非酒精性脂肪性肝炎。”柳叶刀。