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Activation of caspase‐3 in the skeletal muscle during haemodialysis
Author(s) -
Boivin Michel A.,
Battah Shadi I.,
Dominic Elizabeth A.,
KalantarZadeh Kamyar,
Ferrando Arny,
Tzamaloukas Antonios H.,
Dwivedi Rama,
Ma Thomas A.,
Moseley Pope,
Raj Dominic S. C.
Publication year - 2010
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.2010.02347.x
Subject(s) - skeletal muscle , medicine , endocrinology , catabolism , apoptosis , muscle atrophy , proteolysis , caspase , biology , atrophy , chemistry , enzyme , biochemistry , programmed cell death , metabolism
Eur J Clin Invest 2010; 40 (10): 903–910 Abstract Background and Objective Muscle atrophy in end‐stage renal disease (ESRD) may be due to the activation of apoptotic and proteolytic pathways. We hypothesized that activation of caspase‐3 in the skeletal muscle mediates apoptosis and proteolysis during haemodialysis (HD). Materials and Methods Eight ESRD patients were studied before (pre‐HD) and during HD and the findings were compared with those from six healthy volunteers. Protein kinetics was determined by primed constant infusion of L‐(ring 13 C 6 ) Phenylalanine. Results Caspase‐3 activity in the skeletal muscle was higher in ESRD patients pre‐HD than in controls (24966·0 ± 4023·9 vs. 15293·3 ± 2120·0 units, P < 0·01) and increased further during HD (end‐HD) (37666·6 ± 4208·3 units) ( P < 0·001). Actin fragments (14 kDa) generated by caspase‐3 mediated cleavage of actomyosin was higher in the skeletal muscle pre‐HD (68%) and during HD (164%) compared with controls. The abundance of ubiquitinized carboxy‐terminal actin fragment was also significantly increased during HD. Skeletal muscle biopsies obtained at the end of HD exhibited augmented apoptosis, which was higher than that observed in pre‐HD and control samples ( P < 0·001). IL‐6 content in the soluble fraction of the muscle skeletal muscle was increased significantly during HD. Protein kinetic studies showed that catabolism was higher in ESRD patients during HD compared with pre‐HD and control subjects. Muscle protein catabolism was positively associated with caspase‐3 activity and skeletal muscle IL‐6 content. Conclusion Muscle atrophy in ESRD may be due to IL‐6 induced activation of caspase‐3 resulting in apoptosis as well as muscle proteolysis during HD.