Growth factors, muscle function and doping.
ABSTRACT Recently much interest has been shown in developing a treatment of muscle wasting associated with a range of diseases as well as in ageing, which are major medical and socioecomonic problems. Emerging molecular techniques have made it possible to gain a better understanding of the growth factor genes involved and how they are activated by physical activity including the IGF-I gene that can be spliced to give rise to different isoforms, one of which is called MGF that activates muscle progenitor cells that provide the extra nuclei required for muscle hypertrophy, repair and maintenance. This fact that MGF 'kick starts' the hypertrophy process clearly has potential for abuse and has already attracted the attention of body builders.
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ABSTRACT: It has traditionally been believed that resistance training can only induce muscle growth when the exercise intensity is greater than 65 % of the 1-repetition maximum (RM). However, more recently, the use of low-intensity resistance exercise with blood-flow restriction (BFR) has challenged this theory and consistently shown that hypertrophic adaptations can be induced with much lower exercise intensities (<50 % 1-RM). Despite the potent hypertrophic effects of BFR resistance training being demonstrated by numerous studies, the underlying mechanisms responsible for such effects are not well defined. Metabolic stress has been suggested to be a primary factor responsible, and this is theorised to activate numerous other mechanisms, all of which are thought to induce muscle growth via autocrine and/or paracrine actions. However, it is noteworthy that some of these mechanisms do not appear to be mediated to any great extent by metabolic stress but rather by mechanical tension (another primary factor of muscle hypertrophy). Given that the level of mechanical tension is typically low with BFR resistance exercise (<50 % 1-RM), one may question the magnitude of involvement of these mechanisms aligned to the adaptations reported with BFR resistance training. However, despite the low level of mechanical tension, it is plausible that the effects induced by the primary factors (mechanical tension and metabolic stress) are, in fact, additive, which ultimately contributes to the adaptations seen with BFR resistance training. Exercise-induced mechanical tension and metabolic stress are theorised to signal a number of mechanisms for the induction of muscle growth, including increased fast-twitch fibre recruitment, mechanotransduction, muscle damage, systemic and localised hormone production, cell swelling, and the production of reactive oxygen species and its variants, including nitric oxide and heat shock proteins. However, the relative extent to which these specific mechanisms are induced by the primary factors with BFR resistance exercise, as well as their magnitude of involvement in BFR resistance training-induced muscle hypertrophy, requires further exploration.Sports medicine (Auckland, N.Z.). 09/2014;
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ABSTRACT: Expression of insulin-like growth factor 1 (IGF-1) mRNAs splice forms was recently shown to be stimulated by myofibrillar proteins released from the damaged muscle. In this study, we report that individual subfragments of titin and myomesin composed of Fn type III and Ig-like domains can activate expression of two IGF-1 splice forms in cultured myoblasts, both at protein and mRNA level. Competition studies showed that each of the domain-types interact with its own receptor. Induction of IGF-1 expression caused by domains of different types showed dissimilar sensitivity to inhibitors of regulatory cascades. The effect of Fn type III domains was more sensitive to inhibition of Ca(2+)/calmodulin dependent protein kinase, whereas the effect of Ig-like domains showed greater sensitivity to the inhibition of adenylyl cyclase - cAMP - PKA pathway.Molecular and Cellular Endocrinology 08/2014; · 4.04 Impact Factor
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ABSTRACT: Exogenous gene delivery may activate immune system to generate the corresponding antibody, however it is unknown whether all of exogenous genes can induce such immune response at the same level and what would happen when two or more gene delivery simultaneously. To address the question, ELISA was used to determine antibody titers in serum against the most frequent gene doping such as growth hormone (GH), insulin-like growth factor ▪ (IGF-▪) and mechano growth factor (MGF) which were delivered into mice by naked vectors. There was no antibody against GH when saline, pCI-neo or the pCI-GH plasmid alone was injected, but significant antibody was induced when the pCI-GH plasmid was injected in combination with either pCI-MGF or pCI-IGF-I plasmid (pAnalytical Letters 09/2012; · 0.97 Impact Factor