calpain and Kidney-Failure--Chronic

In the course of chronic kidney disease (CKD) the intracellular erythrocyte calcium (Ca (i) (2+) ) level increases along with the progression of the disease. The decreased activity of Ca(2+)-Mg(2+)-dependent ATP-ase (PMCA) and its endogenous modulators calmodulin (CALM), calpain (CANP), and calpastatin (CAST) are all responsible for disturbed calcium metabolism. The aim of the study was to analyze the activity of PMCA, CALM, and the CANP-CAST system in the red blood cells (RBCs) of hemodialyzed (HD) children and to estimate the impact of a single HD session on the aforementioned disturbances. Eighteen patients on maintenance HD and 30 healthy subjects were included in the study. CALM, Ca (i) (2+) levels and basal PMCA (bPMCA), PMCA, CANP, and CAST activities were determined in RBCs before HD, after HD, and before the next HD session. Prior to the HD session, the level of Ca (i) (2+) and the CAST activity were significantly higher, whereas bPMCA, PMCA, and CANP activities and the CALM level were significantly lower than in controls. After the HD session, the Ca (i) (2+) concentration and the CAST activity significantly decreased compared with the basal values, whereas the other parameters significantly increased, although they did not reach the levels of healthy children. The values observed prior to both HD sessions were similar. Ca (i) (2+) homeostasis is severely disturbed in HD children, which may be caused by the reduction in the PMCA activity, CALM deficiency, and CANP-CAST system disturbances. A single HD session improved these disturbances but the effect is transient.

Topics: Adolescent; Ca(2+) Mg(2+)-ATPase; Calcium; Calcium-Binding Proteins; Calmodulin; Calpain; Case-Control Studies; Child; Erythrocytes; Female; Homeostasis; Humans; Kidney Failure, Chronic; Male; Poland; Renal Dialysis; Time Factors; Treatment Outcome

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.. 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.. 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.. 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.

Topics: Adolescent; Calcium; Calcium-Binding Proteins; Calpain; Child; Erythrocytes; Female; Humans; Kidney Failure, Chronic; Male; Plasma Membrane Calcium-Transporting ATPases