Age-dependent degradation of calpastatin in kidney of hypertensive rats

被引:33
作者
Averna, M [1 ]
De Tullio, R [1 ]
Salamino, F [1 ]
Minafra, R [1 ]
Pontremoli, S [1 ]
Melloni, E [1 ]
机构
[1] Univ Genoa, Dept Expt Med, Biochem Sect, I-16132 Genoa, Italy
关键词
D O I
10.1074/jbc.M101936200
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
Hypertensive rats from the Milan strain show a significant decrease in calpastatin activity as compared with normotensive control animals. Calpastatin deficiency is age-related and highly relevant in kidney, heart, and erythrocytes and of minor entity in brain tissue. In normotensives the changes during aging in the levels of calpastatin activity and mRNA are consistent with an increase of calpastatin protein. In hypertensive rats such a relationship during aging is not observed, because a progressive accumulation of mRNA is accompanied by a lower amount of calpastatin protein as compared with control rats. Together with the low level of calpastatin in kidney of hypertensive rats, a progressive accumulation of an active 15-kDa calpastatin fragment, previously shown to represent a typical product of calpain-mediated calpastatin degradation, is also observed. Evidence for such intracellular proteolysis by Ca2+-activated calpain is provided by the normalization of the calpastatin level, up to that of control animals, in hypertensive rats treated with drugs known to reduce both blood pressure and intracellular Ca2+ influx. Further evidence is provided by the disappearance, in these conditions, of the 15-kDa calpastatin fragment. These data allow the conclusion that calpastatin degradation is a relevant part of the overall mechanism for regulating calpain activity.
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收藏
页码:38426 / 38432
页数:7
相关论文
共 48 条
[1]   Changes in intracellular calpastatin localization are mediated by reversible phosphorylation [J].
Averna, M ;
de Tullio, R ;
Passalacqua, M ;
Salamino, F ;
Pontremoli, S ;
Melloni, E .
BIOCHEMICAL JOURNAL, 2001, 354 :25-30
[2]   Calcium ion in skeletal muscle:: Its crucial role for muscle function, plasticity, and disease [J].
Berchtold, MW ;
Brinkmeier, H ;
Müntener, M .
PHYSIOLOGICAL REVIEWS, 2000, 80 (03) :1215-1265
[3]   Calpastatin is up-regulated in response to hypoxia and is a suicide substrate to calpain after neonatal cerebral hypoxia-ischemia [J].
Blomgren, K ;
Hallin, U ;
Andersson, AL ;
Puka-Sundvall, M ;
Bahr, BA ;
McRae, A ;
Saido, TC ;
Kawashima, S ;
Hagberg, H .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (20) :14046-14052
[4]   Calpain activation and inhibition in organotypic rat hippocampal slice cultures deprived of oxygen and glucose [J].
Brana, C ;
Benham, CD ;
Sundstrom, LE .
EUROPEAN JOURNAL OF NEUROSCIENCE, 1999, 11 (07) :2375-2384
[5]   A plethysmographic method for measuring systolic blood pressure in the intact rat [J].
Byrom, FB ;
Wilson, C .
JOURNAL OF PHYSIOLOGY-LONDON, 1938, 93 (03) :301-304
[6]   TRANSCRIPTION OF THE DYSTROPHIN GENE IN HUMAN-MUSCLE AND NON-MUSCLE TISSUES [J].
CHELLY, J ;
KAPLAN, JC ;
MAIRE, P ;
GAUTRON, S ;
KAHN, A .
NATURE, 1988, 333 (6176) :858-860
[7]   CALCIUM-ACTIVATED NEUTRAL PROTEASE (CALPAIN) SYSTEM - STRUCTURE, FUNCTION, AND REGULATION [J].
CROALL, DE ;
DEMARTINO, GN .
PHYSIOLOGICAL REVIEWS, 1991, 71 (03) :813-847
[8]   Rat brain contains multiple mRNAs for calpastatin [J].
De Tullio, R ;
Sparatore, B ;
Salamino, F ;
Melloni, E ;
Pontremoli, S .
FEBS LETTERS, 1998, 422 (01) :113-117
[9]  
De Tullio R, 1999, BIOCHEM J, V343, P467
[10]   Differential degradation of calpastatin by μ- and m-calpain in Ca2+-enriched human neuroblastoma LAN-5 cells [J].
De Tullio, R ;
Averna, M ;
Salamino, F ;
Pontremoli, S ;
Melloni, E .
FEBS LETTERS, 2000, 475 (01) :17-21