[Calpain-calpastatin system in erythrocytes of children with chronic renal failure]

Abstract

Introduction: Disturbances of erythrocyte calcium homeostasis in the course of chronic renal failure (CRF) may result from impaired function of a membrane calcium pump (PMCA). Plasma membrane Ca+2-transport ATP-ase is responsible for maintaining cytoplasmic level of intracellular Ca+2. PMCA activity is regulated by high Ca levels and calmodulin, in case of Ca+2 deficiency--by intracellular cysteine protease--calpain, and its natural inhibitor--calpastatin. The aim of the study was to assess the relationship between the activity of PMCA and calpain-calpastatin system in erythrocytes of children with CRF treated conservatively.

Material and methods: The study was performed on 21 CRF children treated conservatively (gr. I) aged 6-18 years. The control group consisted of 18 healthy age matched children. The parameters evaluated in erythrocytes were as follows: calpain-calpastatin system (Cp-Cs) activity, PMCA activity, level of intracellular Ca (Cai+2) and calmodulin (Ca) activity.

Results: Our investigation revealed: calmodulin concentrations decrement in CRF children (2.08 +/- 0.51 mg/L) vs. controls (4.54 +/- 1.09 nmol/min/mg) (p<0.01), calpain activity in CRF children (60.56 +/- 12.43 U/mg) higher than in controls (45.34 +/- 5.65 U/mg) (p<0.01) and calpastatin activity increment in gr. I (40.03 +/- 10.24 U/mg) vs. control group (20.123.05 U/mg) (p<0.01). Decreased activity of a system containing an enzyme and its inhibitor (calpain-calpastatin) was also observed: 1 : 0.66 ratio in gr. I vs 1:0.4 ratio in controls.

Conclusions: There is a decrease inPMCA activity and an increase of intracellular calcium in erythrocytes of children with mild CRF. The concomitant increment of erythrocyte calpastatin is the cause of disturbances in calpain-calpastatin system, thus unabling normalization of PMCA pump activity.