Novgorodov S A, Gudz T I, Jung D W, Brierley G P
Department of Medical Biochemistry, Ohio State University, Columbus 43210.
Biochem Biophys Res Commun. 1991 Oct 15;180(1):33-8. doi: 10.1016/s0006-291x(05)81250-1.
Cyclosporin A prevents the opening of a nonspecific pore in the inner membrane of liver mitochondria when added prior to Ca2+. In the presence of 10 microM Ca2+ cyclosporin is unable to close the pore and restore the original permeability unless ADP is also added. ADP acts at a high-affinity site (Km 5 microM), corresponding to the adenine nucleotide transporter. This effect of ADP is prevented and reversed by carboxyatractyloside. In the presence of carboxyatractyloside, cyclosporin added with higher concentrations of ADP (Km 70 microM) also can close the pore. This suggests that a lower-affinity ADP-binding component as well as cyclophilin and the adenine nucleotide transporter can modulate the sensitivity of the pore to cyclosporin.
在钙离子之前添加时，环孢素A可防止肝线粒体内膜中出现非特异性孔道。在存在10微摩尔钙离子的情况下，除非同时添加二磷酸腺苷（ADP），否则环孢素无法关闭孔道并恢复原来的通透性。ADP作用于一个高亲和力位点（米氏常数5微摩尔），该位点对应于腺嘌呤核苷酸转运体。羧基苍术苷可阻止并逆转ADP的这种作用。在存在羧基苍术苷的情况下，添加更高浓度ADP（米氏常数70微摩尔）的环孢素也能关闭孔道。这表明，一个低亲和力的ADP结合成分以及亲环蛋白和腺嘌呤核苷酸转运体可以调节孔道对环孢素的敏感性。
