Activation of caspase-3 in the skeletal muscle during haemodialysis

Michel A. Boivin, Shadi I. Battah, Elizabeth A. Dominic, Kamyar Kalantar-Zadeh, Arny Ferrando, Antonios H. Tzamaloukas, Rama Dwivedi, Thomas Ma, Pope Moseley, Dominic S.C. Raj

Research output: Contribution to journalArticle

21 Citations (Scopus)

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 13C6) 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.

Original languageEnglish (US)
Pages (from-to)903-910
Number of pages8
JournalEuropean Journal of Clinical Investigation
Volume40
Issue number10
DOIs
StatePublished - Oct 1 2010

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Caspase 3
Renal Dialysis
Muscle
Skeletal Muscle
Chemical activation
Chronic Kidney Failure
Proteolysis
Interleukin-6
Apoptosis
Actins
Muscular Atrophy
Actomyosin
Kinetics
Muscle Proteins
Biopsy
Phenylalanine
Muscles
Proteins
Healthy Volunteers

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Clinical Biochemistry

Cite this

Boivin, M. A., Battah, S. I., Dominic, E. A., Kalantar-Zadeh, K., Ferrando, A., Tzamaloukas, A. H., ... Raj, D. S. C. (2010). Activation of caspase-3 in the skeletal muscle during haemodialysis. European Journal of Clinical Investigation, 40(10), 903-910. https://doi.org/10.1111/j.1365-2362.2010.02347.x
Boivin, Michel A. ; Battah, Shadi I. ; Dominic, Elizabeth A. ; Kalantar-Zadeh, Kamyar ; Ferrando, Arny ; Tzamaloukas, Antonios H. ; Dwivedi, Rama ; Ma, Thomas ; Moseley, Pope ; Raj, Dominic S.C. / Activation of caspase-3 in the skeletal muscle during haemodialysis. In: European Journal of Clinical Investigation. 2010 ; Vol. 40, No. 10. pp. 903-910.
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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 13C6) 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.",
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Boivin, MA, Battah, SI, Dominic, EA, Kalantar-Zadeh, K, Ferrando, A, Tzamaloukas, AH, Dwivedi, R, Ma, T, Moseley, P & Raj, DSC 2010, 'Activation of caspase-3 in the skeletal muscle during haemodialysis', European Journal of Clinical Investigation, vol. 40, no. 10, pp. 903-910. https://doi.org/10.1111/j.1365-2362.2010.02347.x

Activation of caspase-3 in the skeletal muscle during haemodialysis. / Boivin, Michel A.; Battah, Shadi I.; Dominic, Elizabeth A.; Kalantar-Zadeh, Kamyar; Ferrando, Arny; Tzamaloukas, Antonios H.; Dwivedi, Rama; Ma, Thomas; Moseley, Pope; Raj, Dominic S.C.

In: European Journal of Clinical Investigation, Vol. 40, No. 10, 01.10.2010, p. 903-910.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Activation of caspase-3 in the skeletal muscle during haemodialysis

AU - Boivin, Michel A.

AU - Battah, Shadi I.

AU - Dominic, Elizabeth A.

AU - Kalantar-Zadeh, Kamyar

AU - Ferrando, Arny

AU - Tzamaloukas, Antonios H.

AU - Dwivedi, Rama

AU - Ma, Thomas

AU - Moseley, Pope

AU - Raj, Dominic S.C.

PY - 2010/10/1

Y1 - 2010/10/1

N2 - 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 13C6) 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.

AB - 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 13C6) 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.

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Boivin MA, Battah SI, Dominic EA, Kalantar-Zadeh K, Ferrando A, Tzamaloukas AH et al. Activation of caspase-3 in the skeletal muscle during haemodialysis. European Journal of Clinical Investigation. 2010 Oct 1;40(10):903-910. https://doi.org/10.1111/j.1365-2362.2010.02347.x