Skip to main content
Download PDF

Skeletal muscle expression of creatine kinase-B in end-stage renal disease

Clinical Proteomics volume 1, pages 33–39 (2004)Cite this article

Abstract

The tissue specificity of creatine kinase (CK-MB) has been shown not to be absolute for the myocardium. Unexplained increases of plasma creatine kinase (CK-MB) occur in patients with skeletal muscle disease, confounding the diagnosis of myocardial injury.

The purpose of this study was to examine the expression of CK-B as well as of the nuclear regulatory factor MyoD by Western blot and reverse transcriptase-polymerase chain reaction (RT-PCR) techniques in skeletal muscle biopsies obtained from end-stage renal disease (ESRD) patients.

Quantitation of CKMB mass demonstrated a 35-fold greater concentration in skeletal muscle from ESRD patients (n=45) vs normal skeletal muscles (n=10), (p<0.01). In 22 of 45 ESRD skeletal muscles, CK-B expression was detected by Western blot analysis, molecular weight 46 kDa. In the seven CK-B Western blot positive tissues studied, one demonstrated a RT-PCR amplification product at 111 bp. In contrast, no CK-B expression was detected by either Western blot or RT-PCR in normal skeletal muscles. MyoD expression (98 bp) was found in all ESRD and normal skeletal muscles. The intensity of the MyoD expression was greatest in tissues that demonstrated a higher CKMB mass concentration.

Our findings demonstrate an increase in CK-B protein expression in human skeletal muscle obtained from patients with ESRD, that may in part be controlled by an increase in expression of mRNA for CK-B. The resulting increase in CKMB mass in skeletal muscle from ESRD patients may also be regulated by alterations in expression of the nuclear regulatory protein MyD.

References

  1. Medeiros LJ, Schotte D, Gerson B. Reliability and significance of increased creatine kinase MB isoenzyme in the serum of uremic patients. Am J Clin Pathol 1987;87:103–108.

    PubMed  CAS  Google Scholar 

  2. Jaffe AS, Ritter C, Meltzer V, Harter H, Roberts R. Unmasking artifactual increases in creatine kinase isoenzymes in patients with renal failure. J Lab Clin Med 1984;104:193–202.

    PubMed  CAS  Google Scholar 

  3. Kloosterboer HJ, Stoker-de Vries SA, Hommes FA. The development of creatine kinase in rat skeletal muscle. Changes in isoenzyme ratio, protein, RNA and DNA during development. Enzyme 1976;21:448–458.

    PubMed  CAS  Google Scholar 

  4. Lyons GE, Mühlebach S, Moser A, Masood R, Paterson BM, Buckingham ME, et al. Developmental regulation of creatine kinase gene expression by myogenic factors in embryonic mouse and chick skeletal muscle. Development 1991;113:1017–1029.

    PubMed  CAS  Google Scholar 

  5. Goto I. Creatine phosphokinase isozymes in neuromuscular disorders. Arch Neurol 1974; 31:116–119.

    PubMed  CAS  Google Scholar 

  6. Apple FS, Rogers MA, Casal DC, Sherman WM, Ivy JL. Creatine kinase-MB isoenzyme adaptations in stressed human skeletal muscle of marathon runners. J Appl Physiol 1985;59:149–153.

    PubMed  CAS  Google Scholar 

  7. Apple FS, Billadello JJ. Expression of creatine kinase M and B mRNAs in treadmill trained rat skeletal muscle. Life Sciences 1994;55:585–592.

    PubMed  Article  CAS  Google Scholar 

  8. Yasmineh WG, Ibrahim GA, Abbasnezhad M, Awad EA. Isoenzyme distribution of creatine kinase and lactate dehydrogenase in serum and skeletal muscle in Duchenne muscular dystrophy, collagen disease, and other muscular disorders. Clin Chem 1978;24:1985–1989.

    PubMed  CAS  Google Scholar 

  9. Cox DM, Quinn ZA, McDermott JC. Cell signaling and the regulation of muscle specific gene expression by myocyte enhancer-binding factor 2. Exerc Sport Sci Rev 2000;28:33–38.

    PubMed  CAS  Google Scholar 

  10. Ordahl CP. Developmental regulation of sarcomeric gene expression. Cur Top Dev Biol 1992; 26:145–168.

    CAS  Article  Google Scholar 

  11. Lassar AB, Buskin JN, Lockshon D, Davis RL, Apone S, Hauschka SD, et al. MyoD is a sequence-specific DNA binding protein requiring a region of myc homology to bind to the muscle creatine kinase enhancer. Cell 1989; 58:823–831.

    PubMed  Article  CAS  Google Scholar 

  12. Ricchiuti V, Voss EM, Ney A, Odland M, Anderson PA, Apple FS. Cardiac troponin T isoforms expressed in renal diseased skeletal muscle will not cause false-positive results by the second generation cardiac troponin T assay by Boehringer Mannheim. Clin Chem 1998;44:1919–1924.

    PubMed  CAS  Google Scholar 

  13. Hoang CD, Zhang J, Payne RM, Apple FS. Post-infarction left ventricular remodeling induces changes in creatine kinase mRNA and protein subunit levels in porcine myocardium. Am J Pathol 1997;151:257–264.

    PubMed  CAS  Google Scholar 

  14. Voss EM, Sharkey SW, Gernert AE, Murakami MM, Johnston RB, Hsieh CC, Apple FS. Human and canine cardiac troponin T and creatine kinase-MB distribution in normal and diseased myocardium. Infarct sizing using serum profiles. Arch Pathol Lab Med 1995; 119:799–806.

    PubMed  CAS  Google Scholar 

  15. Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 1987;1:156–159.

    Article  Google Scholar 

  16. Ricchiuti V, Apple FS. RNA expression of cardiac troponin T isoforms in diseased human skeletal muscle. Clin Chem 1999;45:2129–2135.

    PubMed  CAS  Google Scholar 

  17. Mariman EC, Broers CA, Claesen CA, Tesser GI, Wieringa B. Structure and expression of the human creatine kinase B gene. Genomics 1987;1:126–137.

    PubMed  Article  CAS  Google Scholar 

  18. Pearson-White SH. Human MyoD: cDNA and deduced amino acid sequence. Nuc Ac Res 1991;19:1148.

    Article  CAS  Google Scholar 

  19. Floyd M, Ayyar DR, Barwick DD, Hudgson P, Weightman D. Myopathy in chronic renal failure. Quart J Med 1974;43:509–524.

    PubMed  CAS  Google Scholar 

  20. Diesel W, Noakes TD, Swanepoel C, Lambert M. Isokinetic muscle strength predicts maximum exercise tolerance in renal patients on chronic hemodialysis. Am J Kid Dis 1990; 16:109–114.

    PubMed  CAS  Google Scholar 

  21. Diesel W, Emms M, Knight BK, Noakes TD, Swanepoel CR, van Zyl Smit R, et al. Morphologic features of the myopathy associated with chronic renal failure. Am J Kid Dis 1993; 22:677–684.

    PubMed  CAS  Google Scholar 

  22. Tarasuik A, Heimer D, Bark H. Effect of chronic renal failure on skeletal and diaphragmatic muscle contraction. Am Rev Resp Dis 1992;146:1383–1388

    PubMed  CAS  Google Scholar 

  23. Wright WE, Sassoon DA, Lin VK. Myogenin, a factor regulating myogenesis, has a domain homologous to MyoD. Cell 1989;56:607–617.

    PubMed  Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Laboratory Medicine and Pathology, Hennepin County Medical Center, University of Minnesota School of Medicine, 55415, Minneapolis, MN

    Vincent Ricchiuti, Ellen M. Voss & Fred S. Apple

  2. Department of Surgery, Hennepin County Medical Center, University of Minnesota School of Medicine, 55415, Minneapolis, MN

    Arthur Ney & Mark Odland

  3. Clinical Laboratories, Hennepin County Medical Center, 55415, Memphis, MN

    Fred S. Apple

Authors
  1. Vincent Ricchiuti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ellen M. Voss
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Arthur Ney
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mark Odland
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fred S. Apple
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fred S. Apple.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Ricchiuti, V., Voss, E.M., Ney, A. et al. Skeletal muscle expression of creatine kinase-B in end-stage renal disease. Clin Proteom 1, 33–39 (2004). https://doi.org/10.1385/CP:1:1:033

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1385/CP:1:1:033

Key Words

  • CK-MB
  • end-stage renal disease
  • chronic hemodialysis
  • myogenic factor
  • skeletal muscle
  • gene expression

Clinical Proteomics

ISSN: 1559-0275