- Biomarker Discovery and Profiling
- Open Access
Skeletal muscle expression of creatine kinase-B in end-stage renal disease
Clinical Proteomics volume 1, pages 33–39 (2004)
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.
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.
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.
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.
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.
Goto I. Creatine phosphokinase isozymes in neuromuscular disorders. Arch Neurol 1974; 31:116–119.
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.
Apple FS, Billadello JJ. Expression of creatine kinase M and B mRNAs in treadmill trained rat skeletal muscle. Life Sciences 1994;55:585–592.
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.
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.
Ordahl CP. Developmental regulation of sarcomeric gene expression. Cur Top Dev Biol 1992; 26:145–168.
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.
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.
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.
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.
Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 1987;1:156–159.
Ricchiuti V, Apple FS. RNA expression of cardiac troponin T isoforms in diseased human skeletal muscle. Clin Chem 1999;45:2129–2135.
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.
Pearson-White SH. Human MyoD: cDNA and deduced amino acid sequence. Nuc Ac Res 1991;19:1148.
Floyd M, Ayyar DR, Barwick DD, Hudgson P, Weightman D. Myopathy in chronic renal failure. Quart J Med 1974;43:509–524.
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.
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.
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
Wright WE, Sassoon DA, Lin VK. Myogenin, a factor regulating myogenesis, has a domain homologous to MyoD. Cell 1989;56:607–617.
Rights 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
- end-stage renal disease
- chronic hemodialysis
- myogenic factor
- skeletal muscle
- gene expression