FURTHER EVIDENCE THAT CYCLOSPORINE-A PROTECTS MITOCHONDRIA FROM CALCIUM OVERLOAD BY INHIBITING A MATRIX PEPTIDYL-PROLYL CIS-TRANS ISOMERASE - IMPLICATIONS FOR THE IMMUNOSUPPRESSIVE AND TOXIC EFFECTS OF CYCLOSPORINE

被引：217

作者：

GRIFFITHS, EJ ^{[1
]}

HALESTRAP, AP ^{[1
]}

机构：

[1] UNIV BRISTOL,SCH MED SCI,DEPT BIOCHEM,BRISTOL BS8 1TD,AVON,ENGLAND

来源：

BIOCHEMICAL JOURNAL | 1991年 / 274卷

关键词：

D O I：

10.1042/bj2740611

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The K(i) values of cyclosporin 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 mu-M. 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.

引用

页码：611 / 614

页数：4

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