KINETICS OF CYCLOSPORINE-A-INDUCED INHIBITION OF SUCCINATE COENZYME-Q DEHYDROGENASE IN RAT RENAL CORTICAL MITOCHONDRIA

被引:8
作者
LEMMI, CAE
PELIKAN, PCD
GEESAMAN, B
SEAMON, E
KOYLE, M
RAJFER, J
机构
[1] UNIV CALIF LOS ANGELES,LOS ANGELES CTY HARBOR MED CTR,DEPT MED,DIV NEPHROL,TORRANCE,CA 90509
[2] ST JOHNS HEART INST,SANTA MONICA,CA 90404
[3] UNIV CALIF LOS ANGELES,LOS ANGELES CTY HARBOR MED CTR,DEPT SURG,DIV UROL,TORRANCE,CA 90509
[4] UNIV CALIF LOS ANGELES,LOS ANGELES CTY HARBOR MED CTR,DEPT MED,DIV CARDIOL,TORRANCE,CA 90509
来源
BIOCHEMICAL MEDICINE AND METABOLIC BIOLOGY | 1990年 / 43卷 / 03期
关键词
D O I
10.1016/0885-4505(90)90027-X
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 kinetic mechanism of succinate-coenzyme Q dehydrogenase (Complex II) inhibition by cyclosporine A (CS) on rat renal cortical mitochondria was investigated. CS showed two modes of inhibition of Complex II of the mitochondrial electron transport system: (a) a mixed linear noncompetitive inhibition of resting succinate-limited and ADP-stimulated respirations suggesting that CS binds to Complex II at a different site than the substrate, affecting the dissociation constant for the enzyme-substrate complex and (b) a competitive inhibition of the DNP-stimulated electron transport system suggesting competition with the oxidized form of a component of Complex II. CS action to renal mitochondrial Complex II limits its function, an effect which may be related to CS nephrotoxicity. © 1990.
引用
收藏
页码:214 / 225
页数:12
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