环孢菌素A通过抑制一种基质肽基脯氨酰顺反异构酶来保护线粒体免受钙超载的进一步证据。对环孢菌素免疫抑制和毒性作用的启示。
Further evidence that cyclosporin A protects mitochondria from calcium overload by inhibiting a matrix peptidyl-prolyl cis-trans isomerase. Implications for the immunosuppressive and toxic effects of cyclosporin.
作者信息
Griffiths E J, Halestrap A P
机构信息
Department of Biochemistry, School of Medical Sciences, University of Bristol, U.K.
出版信息
Biochem J. 1991 Mar 1;274 ( Pt 2)(Pt 2):611-4. doi: 10.1042/bj2740611.
Abstract
The Ki values of cyclosporins A, G and H for the peptidyl-prolyl cis-trans isomerase (PPIase) of liver and heart mitochondria are about 2, 20 and 500 nM respectively. This parallels their profile as inhibitors of non-specific pore opening of mitochondria induced by supraphysiological Ca2+ concentrations. The novel immunosuppressant FK-506 gave little inhibition of either process at 5 microM. These data support our previous hypothesis [Halestrap & Davidson (1990) Biochem. J. 268, 153-160] that pore opening involves an interaction between matrix PPIase and the adenine nucleotide translocase. It is suggested that this model may help to clarify the mechanism of action of cyclosporin as an immunosuppressant and its toxic effects on the liver and kidney following prolonged therapy.
摘要
环孢菌素A、G和H对肝脏和心脏线粒体的肽基脯氨酰顺反异构酶（PPIase）的Ki值分别约为2、20和500 nM。这与它们作为超生理浓度Ca2+诱导的线粒体非特异性孔开放抑制剂的情况相似。新型免疫抑制剂FK-506在5 microM时对这两个过程的抑制作用很小。这些数据支持了我们之前的假设[Halestrap & Davidson (1990) Biochem. J. 268, 153 - 160]，即孔开放涉及基质PPIase与腺嘌呤核苷酸转位酶之间的相互作用。有人认为，该模型可能有助于阐明环孢菌素作为免疫抑制剂的作用机制及其长期治疗后对肝脏和肾脏的毒性作用。
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本文引用的文献
1
Effect of cyclosporin A on lymphocyte activation by the calcium ionophore A23187.
Immunology. 1983 Nov;50(3):441-6.
2
Fluorimetry of mitochondria in cells vitally stained with DASPMI or rhodamine 6 GO.
Cell Biochem Funct. 1983 Oct;1(3):147-55. doi: 10.1002/cbf.290010306.
3
Autophagic-lysosomal and mitochondrial sequestration of [14C]sucrose. Density gradient distribution of sequestered radioactivity.
Eur J Biochem. 1985 Dec 2;153(2):223-9. doi: 10.1111/j.1432-1033.1985.tb09290.x.
4
Comparison of the pharmacological profiles of cyclosporine, (Nva2)-cyclosporine and (Val2)dihydro-cyclosporine.
Immunology. 1985 Jun;55(2):249-55.
5
Hypothesis about the function of membrane-buried proline residues in transport proteins.
Proc Natl Acad Sci U S A. 1986 Feb;83(4):917-21. doi: 10.1073/pnas.83.4.917.
6
Protein-disulphide isomerase and prolyl isomerase act differently and independently as catalysts of protein folding.
Nature. 1988 Feb 4;331(6155):453-5. doi: 10.1038/331453a0.
7
Inhibition by cyclosporin A of a Ca2+-dependent pore in heart mitochondria activated by inorganic phosphate and oxidative stress.
Biochem J. 1988 Oct 1;255(1):357-60.
8
Cyclosporine--relationship of side effects to mode of action.
Transplantation. 1988 Aug;46(2 Suppl):90S-96S. doi: 10.1097/00007890-198808001-00017.
9
The transmembrane arrangement of the ADP/ATP carrier as elucidated by the lysine reagent pyridoxal 5-phosphate.
Eur J Biochem. 1986 Dec 15;161(3):611-20. doi: 10.1111/j.1432-1033.1986.tb10485.x.
10
Involvement of the ADP/ATP carrier in calcium-induced perturbations of the mitochondrial inner membrane permeability: importance of the orientation of the nucleotide binding site.
Arch Biochem Biophys. 1988 Sep;265(2):249-57. doi: 10.1016/0003-9861(88)90125-7.
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