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

FK-506的免疫控制作用与环孢素a极为相似。近年来，对其免疫控制机制的研究日益深入。如果FK-506进入t细胞，它将与FK-506结合蛋白亲免疫蛋白结合。认为该FK-506-immunophilin复合物通过钙调蛋白和钙调蛋白阻断钙调神经磷酸酶，从而控制t细胞的功能，发挥免疫控制作用。然而，由于该药在有效血中浓度与副作用区浓度特别接近，在许多情况下存在肾毒性问题。然后，我们用sd -大鼠检测PKC参与肾脏组织的可能性。具体而言，我们在屠宰对比用药组肾脏后立即在腹腔内提取FK-506用药组（2.5 mg/g重量用药组，5.0 mg/g重量用药组），分为肾皮质和肾m…然后，我们测量并比较了各组织提取液的PKC活性，并以Bmax （PKC总量）和Kd（分离常数）作为各组织提取液的磷酯受体。目前，FK-506 （5.0mg/g重量）给药组Bmax （PKC总量）有低于对照组的趋势，但差异不显著。在腹腔PKC活性方面，FK-506用药组与对照组无差异。考虑其原因，可能是FK-506用药量不足或与环孢素a的作用机制不同。此外，目前确认PKC至少有7种同工酶，所以FK-506用药并不总是改变所有同工酶，而只是改变某些同工酶。此外，我们将继续这项研究。我们可能需要用色谱法分离PKC同工酶进行实验。少

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