Active Voice: Repeated Eccentric Exercises Modify Human Muscle Proteome
By Bernard Rogister, M.D., Ph.D.

Viewpoints presented in SMB commentaries reflect opinions of the authors and do not necessarily reflect positions or policies of ACSM.

Bernard Rogister, M.D., Ph.D., is Professor of Biochemistry and Physiology in the Medical School at the University of Liège (ULg) in Belgium. As a neuroscientist, his main research focuses on several aspects of developmental neurobiology and stem cells. However, he also has begun collaborating with Jean Louis Croisier, Professor of Physiotherapy (ULg), in order to unravel the molecular mechanisms of muscle damage following eccentric contractions. This commentary presents Dr. Rogister’s views associated with the research article he and his colleagues published in the Dec. 2011 issue of Medicine & Science in Sports & Exercise® (MSSE).

Eccentric (lengthening) muscle contraction frequently induces delayed-onset muscle soreness (DOMS), characterized by muscle pain, impairment of muscle function, stiffness, swelling and reduced range of motion. DOMS typically sets in a few hours after the eccentric exercise and will subsist for a few days, delaying the training program and/or the athlete’s exercise rehabilitation protocol. Histological studies have demonstrated various forms of sarcomeric disruption and membrane leakage that were associated with the presence of creatine kinase in the blood. An intriguing effect is the repeated bout effect. When a muscle has been conditioned by prior eccentric contractions, the magnitude of changes in muscle damage markers after later eccentric contractions is attenuated, constituting a muscle adaptation process.

Although these symptoms and this clinical situation are already well documented, little is known about the molecular mechanisms underlying DOMS or the repeated bout effect. Our recent study in MSSE analyzed the proteome modifications of healthy males’ quadriceps muscles in three conditions: at rest; 24 hours after an injuring exercise protocol (three series of 30 maximal contractions of the quadriceps on an isokinetic dynamometer); and 24 hours after a similar exercise bout preceded either by five eccentric training sessions or not.

The proteome analysis has the advantage of studying the protein modifications, including protein synthesis and degradation, without a pre-established hypothesis, which can sometimes lead to false-negative. Moreover, proteome analysis includes the possible post-translational modifications of proteins (phosphorylation, cleavage, etc.) that are not addressed by the transcriptomic level (analysis of the RNA synthesis, addressing only a possible new protein synthesis).

We observed that the fast isoforms of myosin heavy chain decreased after the first eccentric test and were reduced further after the second test. Moreover, after the test following the five eccentric training sessions, nearly all glycolytic enzymes and the fast isoforms of some contractile and structural proteins were downregulated. These observations suggest that fast glycolytic fibers (fiber IIb) are more fragile in the eccentric exercise and that specific training sessions are characterized by adaptative mechanisms whereby those glycolytic fibers are replaced by aerobic fibers (fiber IIa and/or I). As this adaptation implies the nervous system, these results suggest that there is a stimulation of the fiber conversion by integrated information coming from direct and inverse myotatic reflexes during eccentric exercise. Indeed, using an animal model of DOMS, Hody et al. recently observed such a fiber transition after eccentric but not after concentric contractions (manuscript in preparation).

All these observations reveal the exquisite sensitivity of muscle fibers IIb to eccentric contractions. This should be taken into account, especially in various developmental or therapeutic training protocols for athletes. Indeed, we recently published a paper demonstrating that muscle fatigue during repeated eccentric exercise is predictive of the plasmic CK response.