The Role of Protein Kinase C in Kidney Toxicity by New Immunosuppressant

蛋白激酶 C 在新型免疫抑制剂肾毒性中的作用

• 批准号: 06454456
• 负责人: UENO Akira
• 金额: $ 4.54万
• 依托单位: Yamanashi Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06454456/
• 关键词: Protein Kinase C; immunosuppressant; kidney toxicity; 腎移植

FK-506 does the extremely similar action of immunity control as cyclosporine A. Recently, the research on the mechanism of immunity control has advanced increasingly. If FK-506 enters T-cell, it will combine with FK-506-binding protein, immunophilin. It is thought that this FK-506-immunophilin complex impedes calcineurin by Ca++ and calmodulin, and that it controls the function of T-cell and demonstrates the action of immunity control. However, this medicine poses problems about the kidney toxicity in many cases, because the concentration in effective blood and the one in side-effects region are especially close. And then, we examine the possibility of participation of proteinkinaseC (PKC) in kidney organization, with SD-rat.Specifically, we extract FK-506 medication groups in the abdominal cavity (2.5 mg/g weight medication group, 5.0 mg/g weight medication group) immediately after slaughtering the kidney of the contrast medication group, and divid them into kidney cortex and kidney m … More arrow on the ice. Then, we measure and compare PKC activity of extracted liquid of each organization, Bmax (total amount of PKC) and Kd(separative constant) as the phorbolester receptor of each organization extracted liquid. At present, Bmax (total amount of PKC) of FK-506 (5.0mg/g weight) medication group shows lower tendency than a contrast group, but it is not significant difference. As for PKC activity, there is no difference between FK-506 medication groups in the abdominal cavity and contrast groups. Considering about causes of these, there are possibilities such as the lack of the amount of FK-506 medication or the difference of the action mechanism from cyclosporine A. Besides, at present, it is confirmed that PKC has at least seven kinds of isozymes, so that FK-506 medication does not always make change in all kinds of isozymes but makes change only in some kinds of isozyme.We will continue this research, furthermore. We possibly need to experiment by dividing PKC isozyme with chromatography. Less

FK-506具有与环孢素A极为相似的免疫调节作用。近年来，免疫控制机制的研究日益深入。FK-506进入T细胞后，与FK-506结合蛋白亲免素联合收割机。据认为，这种FK-506-亲免素复合物通过Ca++和钙调蛋白阻碍钙调磷酸酶，并且它控制T细胞的功能并显示免疫控制作用。然而，这种药物在许多情况下会引起肾毒性的问题，因为有效血液中的浓度和副作用区域中的浓度特别接近。然后，我们用SD-大鼠检测蛋白激酶C（PKC）参与肾脏组织化的可能性。具体地，我们在屠宰对照药物组的肾脏后立即在腹腔中提取FK-506药物组（2.5mg/g重量药物组，5.0mg/g重量药物组），并将它们分为肾皮质和肾组织。 ...更多信息 冰上的箭头。然后，测定并比较各组织提取液的PKC活性，以各组织提取液的佛波酯受体Bmax（PKC总量）和Kd（分离常数）为指标。目前，FK-506（5.0mg/g体重）给药组的Bmax（PKC总量）与对照组相比呈下降趋势，但无显著性差异。PKC活性在FK-506腹腔给药组与对照组之间无差异。考虑到这些原因，有可能是FK-506药物用量不足或与环孢素A的作用机制不同。此外，目前已证实PKC至少有7种同工酶，因此FK-506药物并不总是使所有同工酶发生变化，而只是使某些同工酶发生变化，我们将继续这项研究。我们可能需要用层析法分离PKC同工酶进行实验。少