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J Appl Physiol 103: 1103, 2007; doi:10.1152/japplphysiol.00101.2007c
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POINT-COUNTERPOINT

Rebuttal from Drs. Esser and McCarthy

One of the fundamental arguments O'Connor and Pavlath use to support their position for satellite cell addition is that skeletal muscle fibers maintain a relatively fixed myonuclear domain (MND), which is defined as the ratio of cytoplasmic volume per myonucleus (6). However, we believe that MND is not a strong rationale for satellite cell addition because the data supporting a relatively fixed MND are equivocal. For example, Aravamudan et al. (1), reported a poor correlation between cross-sectional area and myonuclear number across all fiber types (r2 = 0.08 to 0.001) with MND values ranging threefold, from 12,000 to 35,000 µm3/myonucleus. These findings confirm elegant work by Wada et al. (9), in which MND values ranged twofold with atrophy, from 7,000 to 14,000 µm3/myonucleus. These are just two examples that demonstrate that MND cannot be assumed to be relatively fixed in skeletal muscle. Thus we feel that MND is a weak foundation for arguing that satellite cell addition is required during hypertrophy.

The other set of data presented in support of a satellite cell requirement come from studies in which {gamma}-irradiation was used as a method to inhibit satellite cell activity (6). While these studies have shown that {gamma}-irradiation treatment can inhibit growth of skeletal muscle they do not provide sufficient data to conclude that the lack of growth is due to effects only on satellite cells. Our primary concern is that {gamma}-irradiation is a very messy experimental intervention that is known to produce deleterious effects to all cell types through both genomic and non-genomic mechanisms (25). We are not aware of any studies, including the ones cited, that assess the potential contribution of the non-genomic effects such as mRNA:polysome interactions or free radical-mediated mitochondrial disruptions (3, 4). In addition, O'Connor and Pavlath do not provide much evidence that the growth potential of skeletal muscle, following irradiation, is due to genomic effects specific to satellite cells only. They cite only one study that reported no change in a single marker of endothelial cells (CD31 staining) to argue that only the satellite cell population is impaired by irradiation (6). We feel that analysis of only one marker for one cell type is very limited and does not come close to demonstrating that satellite cells are the only cells within skeletal muscle that are affected by irradiation. Consideration of other cell types is important as recent studies have implicated the contribution of macrophages as well as endothelial cells to skeletal muscle growth (7, 8).

REFERENCES

  1. Aravamudan B, Mantilla CB, Zhan WZ, Sieck GC. Denervation effects on myonuclear domain size of rat diaphragm fibers. J Appl Physiol 100: 1617–1622, 2006.[Abstract/Free Full Text]
  2. Coates PJ, Lorimore SA, Wright EG. Damaging and protective cell signalling in the untargeted effects of ionizing radiation. Mutat Res 568: 5–20, 2004.[Web of Science][Medline]
  3. Kim GJ, Chandrasekaran K, Morgan WF. Mitochondrial dysfunction, persistently elevated levels of reactive oxygen species and radiation-induced genomic instability: a review. Mutagenesis 21: 361–367, 2006.[Abstract/Free Full Text]
  4. Lu X, de la Pena L, Barker C, Camphausen K, Tofilon PJ. Radiation-induced changes in gene expression involve recruitment of existing messenger RNAs to and away from polysomes. Cancer Res 66: 1052–1061, 2006.[Abstract/Free Full Text]
  5. Nagar S, Corcoran JJ, Morgan WF. Evaluating the delayed effects of cellular exposure to ionizing radiation. Methods Mol Biol 314: 43–50, 2006.[Medline]
  6. O'Connor R, Pavlath G. Point: Satellite cell addition is obligatory for skeletal muscle hypertrophy. J Appl Physiol. In press.
  7. Takahashi A, Kureishi Y, Yang J, Luo Z, Guo K, Mukhopadhyay D, Ivashchenko Y, Branellec D, Walsh K. Myogenic Akt signaling regulates blood vessel recruitment during myofiber growth. Mol Cell Biol 22: 4803–4814, 2002.[Abstract/Free Full Text]
  8. Tidball JG, Wehling-Henricks M. Macrophages promote muscle membrane repair and muscle fibre growth and regeneration during modified muscle loading in mice in vivo. J Physiol 578: 327–336, 2007.[Abstract/Free Full Text]
  9. Wada KI, Takahashi H, Katsuta S, Soya H. No decrease in myonuclear number after long-term denervation in mature mice. Am J Physiol Cell Physiol 283: C484–C488, 2002.[Abstract/Free Full Text]




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