Changes in Urinary Titin Fragment in Response to Different Types of Dynamic Eccentric Exercises

Abstract

The urinary level of the titin fragment has been considered a non-invasive and sensitive biomarker for muscle damage in clinical cases. However, there is little evidence regarding changes in the urinary titin fragment in response to exercise-induced muscle damage. In this study, we aimed to investigate whether the urinary titin fragment reflects the magnitude of muscle damage induced by two lower-limb eccentric exercises. In this study, healthy young male subjects performed drop jump (n=9) and eccentric ergometer exercise (n=9). Blood and urine samples were collected at various time points before and after the exercises. Although perceived muscle soreness assessed by sit-to-stand tasks was increased at 24 h and 48 h after both drop jump and the eccentric ergometer exercise groups, the pressure pain threshold was not changed. Changes of the urinary titin fragment, plasma myomesin 3 fragments, creatine kinase (CK), and myoglobin (Mb) after the eccentric exercises were increased but not statistically significant. Meanwhile, we found that the changes in the urinary titin fragment levels in response to both drop jump and the eccentric ergometer exercise were correlated with those of plasma CK and Mb levels. These results provide evidence that the urinary titin fragment level is a non-invasive biomarker reflecting the magnitude of eccentric exercise-induced muscle damage.

Key words

connectin - titin - eccentric exercise - muscle damage - biomarkers

^* equal contribution

Publication History

Received: 31 March 2020

Accepted: 18 September 2020

Article published online:
29 October 2020

• References

• 1 Howell JN, Chleboun G, Conatser R. Muscle stiffness, strength loss, swelling and soreness following exercise-induced injury in humans. J Physiol 1993; 464: 183-196
• 2 Highton JM, Twist C, Eston RG. The effects of exercise-induced muscle damage on agility and sprint running performance. J Exerc Sci Fit 2009; 7: 24-30
• 3 Wallace GQ, McNally EM. Mechanisms of muscle degeneration, regeneration, and repair in the muscular dystrophies. Annu Rev Physiol 2009; 71: 37-57
• 4 Brancaccio P, Lippi G, Maffulli N. Biochemical markers of muscular damage. Clin Chem Lab Med 2010; 48: 757-767
• 5 Rouillon J, Poupiot J, Zocevic A. et al. Serum proteomic profiling reveals fragments of MYOM3 as potential biomarkers for monitoring the outcome of therapeutic interventions in muscular dystrophies. Hum Mol Genet 2015; 24: 4916-4932
• 6 Nosaka K, Newton M, Sacco P. Delayed-onset muscle soreness does not reflect the magnitude of eccentric exercise-induced muscle damage. Scand J Med Sci Sports 2002; 12: 337-346
• 7 Cacchiarelli D, Legnini I, Martone J. et al. miRNAs as serum biomarkers for Duchenne muscular dystrophy. EMBO Mol Med 2011; 3: 258-265
• 8 Rouillon J, Zocevic A, Leger T. et al. Proteomics profiling of urine reveals specific titin fragments as biomarkers of Duchenne muscular dystrophy. Neuromuscul Disord 2014; 24: 563-573
• 9 Awano H, Matsumoto M, Nagai M. et al. Diagnostic and clinical significance of the titin fragment in urine of Duchenne muscular dystrophy patients. Clin Chim Acta 2018; 476: 111-116
• 10 Maruyama N, Asai T, Abe C. et al. Establishment of a highly sensitive sandwich ELISA for the N-terminal fragment of titin in urine. Sci Rep 2016; 6: 39375
• 11 Robertson AS, Majchrzak MJ, Smith CJ. et al. Dramatic elevation in urinary amino terminal titin fragment excretion quantified by immunoassay in Duchenne muscular dystrophy patients and in dystrophin deficient rodents. Neuromuscul Disord 2017; 27: 635-645
• 12 Kanda K, Sakuma J, Akimoto T. et al. Detection of titin fragments in urine in response to exercise-induced muscle damage. PLoS One 2017; 12: e0181623
• 13 Harriss DJ, Macsween A, Atkinson G. Ethical standards in sport and exercise science research: 2020 update. Int J Sports Med 2019; 40: 813-817
• 14 Olek RA, Kujach S, Ziemann E. et al. Adaptive changes after 2 weeks of 10-s sprint interval training with various recovery times. Front Physiol 2018; 9: 392
• 15 Miyama M, Nosaka K. Influence of surface on muscle damage and soreness induced by consecutive drop jumps. J Strength Cond Res 2004; 18: 206-211
• 16 Sellwood KL, Brukner P, Williams D. et al. Ice-water immersion and delayed-onset muscle soreness: a randomised controlled trial. Br J Sports Med 2007; 41: 392-397
• 17 Chesterton LS, Sim J, Wright CC. et al. Interrater reliability of algometry in measuring pressure pain thresholds in healthy humans, using multiple raters. Clin J Pain 2007; 23: 760-766
• 18 Vieira A, Siqueira AF, Ferreira-Junior JB. et al. The effect of water temperature during cold-water immersion on recovery from exercise-induced muscle damage. Int J Sports Med 2016; 37: 937-943
• 19 Wada S, Kato Y, Okutsu M. et al. Translational suppression of atrophic regulators by microRNA-23a integrates resistance to skeletal muscle atrophy. J Biol Chem 2011; 286: 38456-38465
• 20 Yamaguchi S, Suzuki K, Kanda K. et al. Changes in urinary titin N-terminal fragments as a biomarker of exercise-induced muscle damage in the repeated bout effect. J Sci Med Sport 2020; 23: 536-540
• 21 Yamaguchi S, Suzuki K, Inami T. et al. Changes in urinary titin N-terminal fragment concentration after concentric and eccentric exercise. J Sports Sci Med 2020; 19: 121-129
• 22 Yamaguchi S, Suzuki K, Kanda K. et al. N-terminal fragments of titin in urine as a biomarker for eccentric exercise-induced muscle damage. J Phys Fitness. Sports Med 2020; 9: 21-29
• 23 Bruunsgaard H, Galbo H, Halkjaer-Kristensen J. et al. Exercise-induced increase in serum interleukin-6 in humans is related to muscle damage. J Physiol 1997; 499: 833-841
• 24 Chen TC, Lin KY, Chen HL. et al. Comparison in eccentric exercise-induced muscle damage among four limb muscles. Eur J Appl Physiol 2011; 111: 211-223
• 25 Nosaka K, Clarkson PM. Variability in serum creatine kinase response after eccentric exercise of the elbow. Int J Sports Med 1996; 17: 120-127
• 26 Clarkson PM, Ebbeling C. Investigation of serum creatine kinase variability after muscle-damaging exercise. Clin Sci (Lond) 1988; 75: 257-261
• 27 Fridén J, Sjostrom M, Ekblom B. Myofibrillar damage following intense eccentric exercise in man. Int J Sports Med 1983; 4: 170-176
• 28 Clarkson PM, Hoffman EP, Zambraski E. et al. ACTN3 and MLCK genotype associations with exertional muscle damage. J Appl Physiol (1985) 2005; 99: 564-269
• 29 Childers MK, McDonald KS. Regulatory light chain phosphorylation increases eccentric contraction-induced injury in skinned fast-twitch fibers. Muscle Nerve 2004; 29: 313-317
• 30 Marchettini P. Muscle pain: Animal and human experimental and clinical studies. Muscle Nerve 1993; 16: 1033-1039
• 31 Pyne DB. Exercise-induced muscle damage and inflammation: A review. Aust J Sci Med Sport 1994; 26: 49-58
• 32 Peñailillo L, Blazevich AJ, Nosaka K. Factors contributing to lower metabolic demand of eccentric compared with concentric cycling. J Appl Physiol (1985) 2017; 123: 884-893
• 33 LaStayo P, Marcus R, Dibble L. et al. Eccentric exercise in rehabilitation: Safety, feasibility, and application. J Appl Physiol (1985) 2014; 116: 1426-1434
• 34 Heckel Z, Atlasz T, Tékus É. et al. Monitoring exercise-induced muscle damage indicators and myoelectric activity during two weeks of knee extensor exercise training in young and old men. PLoS One 2019; 14: e0224866
• 35 Chen HY, Chen YC, Tung K. et al. Effects of caffeine and sex on muscle performance and delayed-onset muscle soreness after exercise-induced muscle damage: a double-blind randomized trial. J Appl Physiol (1985) 2019; 127: 798-805