Calpain-3 is activated following eccentric exercise

Abstract

LETTERS TO THE EDITORCalpain-3 is activated following eccentric exerciseRobyn M. Murphy and Graham D. LambRobyn M. Murphy and Graham D. LambDepartment of Zoology, La Trobe University, Melbourne, Victoria, AustraliaPublished Online:01 Jun 2009https://doi.org/10.1152/japplphysiol.00239.2009MoreSectionsPDF (28 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations to the editor: In a recent article by Lehti et al. (3) the effect of fatiguing exercise on the mRNA expression of a number of skeletal muscle proteins was examined. In the discussion it was stated that in a study conducted by our laboratory, calpain-3 mRNA was increased 24 h after a bout of eccentric exercise (4). It needs to be pointed out that this was NOT a finding in that manuscript and there were no mRNA measurements made in that study. We in fact measured calpain-3 protein and reported the first physiological activation of calpain-3, which occurred 24 h after the single bout of eccentric exercise in humans. These findings support a role for calpain-3 in sarcomeric remodeling following eccentric exercise. We used autolysis as a measure of calpain-3 activity because it is known that calpain-3 must be autolysed for it to become activated (2). Recently, we (5) showed that calpain-3 is activated when in the presence of only ∼200 nM Ca2+ for 1 h, although it was not activated over the same period of time in the presence of ∼50 nM Ca2+.The finding of no change or as stated “a decreasing trend in calpain-3 mRNA expression was seen” 2 days after the exercise protocol (3) is similar to that previously reported following eccentric exercise (1). In the latter study, the authors pointed out that mRNA measurements are not necessarily indicative of enzyme activity and protein levels, although some correlation between the mRNA and protein levels for m-calpain has been reported (6). There is no evidence for such associations among mRNA, protein levels, or protein activity for the skeletal muscle specific calpain-3. The previous findings (1, 3, 4) might suggest that there is indeed no correlation between calpain-3 mRNA and protein levels and that if knowledge is to be obtained about the functional role of calpain-3 in skeletal muscle then autolysis of the full-length endogenously expressed protein needs to be measured.REFERENCES1 Feasson L, Stockholm D, Freyssenet D, Richard I, Duguez S, Beckmann JS, Denis C. Molecular adaptations of neuromuscular disease-associated proteins in response to eccentric exercise in human skeletal muscle. J Physiol 543: 297–306, 2002.Crossref | PubMed | ISI | Google Scholar2 Garcia Diaz BE, Moldoveanu T, Kuiper MJ, Campbell RL, Davies PL. Insertion sequence 1 of muscle-specific calpain, p94, acts as an internal propeptide. J Biol Chem 279: 27656–27666, 2004.Crossref | PubMed | ISI | Google Scholar3 Lehti M, Kivela R, Komi PV, Komulainen J, Kainulainen H, Kyrolainen H. Effects of fatiguing jumping exercise on mRNA expression of titin-complex proteins and calpains. J Appl Physiol 106: 1419–1424, 2009.Link | ISI | Google Scholar4 Murphy RM, Goodman CA, McKenna MJ, Bennie J, Leikis M, Lamb GD. Calpain-3 is autolyzed and hence activated in human skeletal muscle 24 h following a single bout of eccentric exercise. J Appl Physiol 103, 926–931, 2007.Link | ISI | Google Scholar5 Murphy RM, Lamb GD. Endogenous calpain-3 activation is primarily governed by small increases in resting cytoplasmic [Ca2+] and is not dependent on stretch. J Biol Chem 284: 7811–7819, 2009.Crossref | PubMed | ISI | Google Scholar6 Spencer MJ, Lu B, Tidball JG. Calpain II expression is increased by changes in mechanical loading of muscle in vivo. J Cell Biochem 64: 55–66, 1997.Crossref | PubMed | ISI | Google ScholarAUTHOR NOTESAddress for reprint requests and other correspondence: R. M. Murphy, Dept. of Zoology, La Trobe Univ., Melbourne, Victoria, 3086 Australia (e-mail: [email protected]) Download PDF Previous Back to Top Next FiguresReferencesRelatedInformation Cited ByDoes Obesity Affect the Severity of Exercise-Induced Muscle Injury?Journal of Obesity & Metabolic Syndrome, Vol. 30, No. 2Insertion sequence 1 from calpain-3 is functional in calpain-2 as an internal propeptideJournal of Biological Chemistry, Vol. 293, No. 46Calpain-3-mediated regulation of the Na+-Ca2+ exchanger isoform 327 October 2015 | Pflügers Archiv - European Journal of Physiology, Vol. 468, No. 2SERCA1 overexpression minimizes skeletal muscle damage in dystrophic mouse modelsDavi A. G. Mázala, Stephen J. P. Pratt, Dapeng Chen, Jeffery D. Molkentin, Richard M. Lovering, and Eva R. Chin1 May 2015 | American Journal of Physiology-Cell Physiology, Vol. 308, No. 9Calpains, skeletal muscle function and exerciseClinical and Experimental Pharmacology and Physiology, Vol. 37, No. 3Reply to Murphy and LambMaarit Lehti, Riikka Kivelä, Paavo Komi, Jyrki Komulainen, Heikki Kainulainen, and Heikki Kyröläinen1 June 2009 | Journal of Applied Physiology, Vol. 106, No. 6 More from this issue > Volume 106Issue 6June 2009Pages 2068-2068 Copyright & PermissionsCopyright © 2009 the American Physiological Societyhttps://doi.org/10.1152/japplphysiol.00239.2009PubMed19470844History Published online 1 June 2009 Published in print 1 June 2009 Metrics