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Title: The exercise-induced expression of heat shock proteins in human skeletal muscle : the role of evaluated muscle and core temperature and the influence of training status
Author: Morton, James Peter.
Awarding Body: Liverpool John Moores University
Current Institution: Liverpool John Moores University
Date of Award: 2006
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Abstract:
Skeletal muscle adapts to the stress of contractile activity with a change in gene expression to yield a family of highly conserved cytoprotective proteins known as heat shock proteins (HSPs). These proteins function to restore cellular homeostasis and to protect the cell against further insults. The exercise-induced stress response of rodent muscle is now relatively well defined. Comparable data from human studies, however, are extremely limited and the stress response of human skeletal muscle is far from understood. The main aims of this thesis were to characterise the time-course and magnitude of response of the exercise-induced production of the major HSP families in human skeletal muscle. The role of increased muscle and core temperature in contributing to the exercise-induced production of HSPs was also investigated. Finally, the effects of training status on baseline muscle content of the major HSP families and on the magnitude of the exercise-induced stress response was also examined. All of the exercise related studies undertaken in this thesis employed a 45 min running exercise protocol on a motorised treadmill at an intensity corresponding to the lactate threshold. This protocol was characterised as `non-damaging' in nature as it resulted in no overt structural or functional damage to the muscle of young untrained (27 ±5 years), recreationally active (25 ±2 years) or aerobically trained male subjects (27 ±6 years), as evidenced by indirect indicators of muscle damage such as circulating levels of creatine kinase and maximal quadriceps isometric muscle force. The time-course and magnitude of the exercise-induced response of the major HSP families were characterised in an active young (24 ±4 years) male population. Muscle biopsies were obtained from the vastus lateralis muscle immediately prior to and at 24 h, 48 h, 72 h and 7 days post-exercise. Exercise induced significant and individually variable increases in HSP70, HSC70 and HSP60 content with peak increases typically occurring at 48 h post-exercise. In contrast, exercise did not induce significant increases in either HSP27, aB-crystallin, manganese superoxide dismutase (MnSOD) protein content or the activity of superoxide dismutase (SOD) and catalase. When examining baseline protein levels, HSC70, HSP27 and aB-crystallin appeared consistently expressed between subjects whereas HSP70 and MnSOD displayed marked individual variation of up to 3 and 1.5 fold, respectively. These data demonstrate a differential effect of aerobic exercise on specific HSPs. Data also demonstrate an individual variation in both basal HSP levels and in the magnitude of the stress response to acute exercise, which may be related to individual differences in training status. The role of increased muscle and core temperature in contributing to the exerciseinduced production of HSPs were subsequently investigated. Active young males (23 A: 3 years) underwent a passive heating protocol of 1h duration during which the temperature of the core and vastus lateralis muscle were increased to similar levels as that occurring during exercise. One limb was immersed in a tank containing warm water whilst the contra-lateral limb remained outside the tank and was not exposed to heat stress. Muscle biopsies were obtained from the vastus lateralis of both legs immediately prior to and at 48 h and 7 days post-heating. The heating protocol induced significant increases in rectal and muscle temperature of the heated leg whilst muscle temperature of the non-heated limb showed no significant change followingheating. The heating protocol failed to induce significant increases in muscle content of HSP70, HSC70, HSP60, HSP27, aB-crystallin, MnSOD protein content or the activity of SOD and catalase in either the heated or non-heated leg. Data demonstrate that increases in both systemic and local muscle temperature per se appear not to be mediating the exercise-induced production of HSPs and suggest that non-heat-stress factors associated with muscle contractile activity are of more importance in mediating this response. The influences of aerobic training status on the basal levels of HSPs and on the magnitude of the exercise-induced stress response were also investigated. Muscle biopsies were obtained from the vastus lateralis of young trained (28 ±6 years) and untrained (29 ±6 years) male subjects immediately prior to and at 48 h and 7 days post-exercise. When comparing muscles at rest, trained subjects had significantly higher levels of aB-crystallin, HSP60 and MnSOD compared with untrained subjects. Trained subjects also had a tendency for higher levels of HSP70, HSC70 and total SOD activity compared with untrained subjects. In contrast to the active population examined earlier, neither the trained nor untrained subjects exhibited a stress response to exercise. The absence of a stress response in trained subjects is likely due to the increase in baseline defences and the customary nature of the exercise protocol. The absence of a stress response in untrained subjects may be due to the failure of the exercise protocol to elicit a proposed critical threshold intensity that is required to induce increases in muscle HSP content. This thesis has provided novel data for the literature and has significantly advanced our understanding of the exercise-induced stress response of human skeletal muscle. Future research should examine the effects of exercise intensity on muscle HSP production and investigate the role of reactive oxygen species in contributing to the response. The wider implications of the exercise-induced production of HSPs, such as their potential cytoprotective properties against related and non-related stressors, should also be examined. Key Words: molecular chaperones, oxidative stress, hyperthermia, stress proteins
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.438773  DOI: Not available
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