ABSTRACT
OBJECTIVE: During muscle development or regeneration, myocytes produce nerve growth factor (NGF) as well as its tyrosine-kinase and p75-neurotrophin (p75NTR) receptors. It has been published that the p75NTR receptor could represent a key regulator of NGF-mediated myoprotective effect on satellite cells, but the precise function of NGF/p75 signaling pathway on myogenic cell proliferation, survival and differentiation remains fragmented and controversial. Here, we verified the role of NGF in the growth, survival and differentiation of p75NTR-expressing L6C5 myogenic cells, specifically inquiring for the putative involvement of the nuclear factor κB (NFκB) and the small heat shock proteins (sHSPs) αB-crystallin and Hsp27 in these processes. RESULTS: Although NGF was not effective in modulating myogenic cell growth or survival in both standard or stress conditions, we demonstrated for the first time that, under serum deprivation, NGF sustained the activity of some key enzymes involved in energy metabolism. Moreover, we confirmed that NGF promotes myogenic fusion and expression of the structural protein myosin heavy chain while modulating NFκB activation and the content of sHSPs correlated with the differentiation process. We conclude that p75NTR is sufficient to mediate the modulation of L6C5 myogenic differentiation by NGF in term of structural, metabolic and functional changes.
Subject(s)
Energy Metabolism/drug effects , Muscle Fibers, Skeletal/drug effects , Myoblasts/drug effects , NF-kappa B/genetics , Nerve Growth Factor/pharmacology , Receptors, Nerve Growth Factor/genetics , 3-Hydroxyacyl-CoA Dehydrogenase/genetics , 3-Hydroxyacyl-CoA Dehydrogenase/metabolism , Animals , Cell Cycle/drug effects , Cell Cycle/genetics , Cell Differentiation/drug effects , Cell Fusion , Cell Line , Citrate (si)-Synthase/genetics , Citrate (si)-Synthase/metabolism , Crystallins/genetics , Crystallins/metabolism , Culture Media, Serum-Free/pharmacology , Energy Metabolism/genetics , Gene Expression Regulation , HSP27 Heat-Shock Proteins/genetics , HSP27 Heat-Shock Proteins/metabolism , L-Lactate Dehydrogenase/genetics , L-Lactate Dehydrogenase/metabolism , Microtubule-Associated Proteins/genetics , Microtubule-Associated Proteins/metabolism , Muscle Development/drug effects , Muscle Development/genetics , Muscle Fibers, Skeletal/cytology , Muscle Fibers, Skeletal/metabolism , Myoblasts/cytology , Myoblasts/metabolism , Myosin Heavy Chains/genetics , Myosin Heavy Chains/metabolism , NF-kappa B/metabolism , Nerve Growth Factor/metabolism , Nerve Tissue Proteins , Rats , Receptors, Growth Factor , Receptors, Nerve Growth Factor/metabolism , Signal TransductionABSTRACT
PURPOSE: Polymorphic variation in the angiotensin-converting enzyme (ACE) and α-actinin-3 (ACTN3) genes has been reported to be associated with endurance and/or power-related human performance. Our aim was to investigate whether polymorphisms in ACE and ACTN3 are associated with elite swimmer status in Caucasian and East Asian populations. METHODS: ACE I/D and ACTN3 R577X genotyping was carried out for 200 elite Caucasian swimmers from European, Commonwealth, Russian, and American cohorts (short and middle distance, ≤400 m, n = 130; long distance, >400 m, n = 70) and 326 elite Japanese and Taiwanese swimmers (short distance, ≤100 m, n = 166; middle distance, 200-400 m, n = 160). Genetic associations were evaluated by logistic regression and other tests accommodating multiple testing adjustment. RESULTS: ACE I/D was associated with swimmer status in Caucasians, with the D allele being overrepresented in short-and-middle-distance swimmers under both additive and I-allele-dominant models (permutation test P = 0.003 and P = 0.0005, respectively). ACE I/D was also associated with swimmer status in East Asians. In this group, however, the I allele was overrepresented in the short-distance swimmer group (permutation test P = 0.041 and P = 0.0098 under the additive and the D-allele-dominant models, respectively). ACTN3 R577X was not significantly associated with swimmer status in either Caucasians or East Asians. CONCLUSIONS: ACE I/D associations were observed in these elite swimmer cohorts, with different risk alleles responsible for the associations in swimmers of different ethnicities. The functional ACTN3 R577X polymorphism did not show any significant association with elite swimmer status, despite numerous previous reports of associations with "power/sprint" performance in other sports.
