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Denervation modulated changes in mouse skeletal muscle RNA concentration

Virchows Archiv B

Summary

We have examined normal and denervated mouse skeletal muscle for histological evidence of changes in RNA concentration using acridine orange/nucleic acid fluorescence. In denervated muscle, cytoplasmic RNA concentration increases dramatically. The earliest increase is in the subsarcolemmal region, 7 days after denervation. By 28 days after denervation, the increase in RNA is distributed throughout the cytoplasm of the atrophic cells, non-atrophic cells show little or no increase. Prior to the increase in cytoplasmic RNA concentration, many myocyte nuclei exhibit enlarged nucleoli, indicative of active ribosomal RNA synthesis. Such active nucleoli are present throughout the 42 day study period. We conclude that both new RNA synthesis, and preferential accumulation of cytoplasmic RNA are prominent events in denervation atrophy. There is an ordered progression from nucleolar synthesis to subsarcolemmal accumulation to diffuse accumulation in atrophying cells. These observations complement biochemical findings of others which indicate an increase in both RNA and protein synthesis after denervation.

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References

  • Adams RD (1975) Diseases of muscle. A study in pathology. Harper and Row, New York

    Google Scholar 

  • Bowman DC, Martin AW (1970) Nucleic acid and protein synthesis after denervation of the rat hemidiaphragm. Exp Neurol 33:256–262

    Article  Google Scholar 

  • Brockes JP, Hall AZ (1975) Synthesis of acetylcholine receptor by denervated rat diaphragm muscle. Proc Nat Acad Sci 72:1368–1372

    Article  PubMed  CAS  Google Scholar 

  • Cullen MJ, Pluskai MG (1977) Early changes in the ultrastructure of denervated rat skeletal muscle. Exp Neurol 56:115–131

    Article  PubMed  CAS  Google Scholar 

  • Dubowitz V, Brooke MH (1973) Muscle biopsy: a modern approach. Saunders, Philadelphia

    Google Scholar 

  • Engel AG, Stonnington HH (1974) Morphologic effects of denervation of muscle: A quantitative ultrastructural study. Ann New York Acad Sci 228:68–88

    Article  CAS  Google Scholar 

  • Fambrough DM (1970) Acetylcholine sensitivity of muscle fiber membranes: Mechanism of regulation by motorneurons. Science 168:372–373

    Article  PubMed  CAS  Google Scholar 

  • Gauthier GF, Dunn RA (1973) Ultrastructural and cytochemical features of mammalian skeletal muscle fibers following denervation. J Cell Sci 12:525–547

    PubMed  CAS  Google Scholar 

  • Gauthier GF, Schaeffer SF (1974) Ultrastructural and cytochemical manifestations of protein synthesis in the peripheral sarcoplasm of denervated and newborn skeletal muscle fibers. J Cell Sci 14:113–137

    PubMed  CAS  Google Scholar 

  • Goldspink DF (1976) The effects of denervation on protein turnover of rat skeletal muscle. Biochem J 156:71–80

    PubMed  CAS  Google Scholar 

  • Goldspink DF (1978) The influence of passive stretch on the growth and protein turnover of the denervated extensor digitorum longus muscle. Biochem J 174:595–602

    PubMed  CAS  Google Scholar 

  • Goldspink DF, Harris JB, Park DC, Parsons ME, Pennington RJ (1971) Quantitative enzyme studies in denervated extensor digitorum longus and soleus muscle of rats. Int J Biochem 2:427–403

    Article  CAS  Google Scholar 

  • Grampp W, Harris JB, Thesleff S (1972) Inhibition of denervation changes in skeletal muscle by blockers of protein synthesis. J Physiol 221:743–754

    PubMed  CAS  Google Scholar 

  • Held IR (1978) Stimulation of nuclear RNA synthesis in denervated skeletal muscles. J Neurochem 30:1239–1243

    Article  PubMed  CAS  Google Scholar 

  • Ionescu V, Lewis R, Schottelius B (1975) Neurogenic control of muscle ribosomal protein synthesis. Acta Neurol Scand 51:253–267

    Google Scholar 

  • Little BW, Webster CS (1980) Denervation modulated changes in skeletal muscle RNA concentration-a histochemical study. Fed Proc 39:418

    Google Scholar 

  • Manchester KL (1974) Effect of insulin and denervation on the activity of ribosomes of rat diaphragm muscle. Biochemistry 13:3062–3068

    Article  PubMed  CAS  Google Scholar 

  • Manchester KL, Harris EJ (1970) Effect of denervation on the synthesis of ribonucleic acid in rat diaphragm muscle. Biochem J 108:177–183

    Google Scholar 

  • Manolov S, Ovtsharoff W (1973) Ultrastructural changes in the nuclei of denervated muscles in the rat. Z Mikroshk-Anat Forsch 87:815–828

    CAS  Google Scholar 

  • McCaman MW (1963) Enzyme studies in skeletal muscle in mice with hereditary muscular dystrophy. Am J Physiol 205:897–901

    PubMed  CAS  Google Scholar 

  • Millward DJ, Garlick PJ, James WPT, Nnanygelugo DO, Ryatt JS (1973) Relationship between protein synthesis and RNA content in skeletal muscle. Nature 241:204–205

    Article  PubMed  CAS  Google Scholar 

  • Muchnik S, Ruarte AC, Kotsias BA (1973) Effects of actinomycin D on fibrillation activity in denervated skeletal muscle of the rat. Life Sci 13:1763–1770

    Article  PubMed  CAS  Google Scholar 

  • Perl DP, Little BW (1980) Acridine orange nucleic acid fluorescence in routine muscle biopsy evaluation. Arch Neurol 37:641–644

    PubMed  CAS  Google Scholar 

  • Politoff AL, Blitz AL (1978) Neurotrophic control of RNA synthesis in amphibion striated muscle. Brain Res 151:561–570

    Article  PubMed  CAS  Google Scholar 

  • Turner LV, Manchester KL (1973) Effect of denervation hypertrophy in rat diaphragm muscle on the activity of ribosomes and sap fractions in protein synthesis. Biochim Biophys Acta 299:612–620

    PubMed  CAS  Google Scholar 

  • Turner LV, Garlick PJ (1974) The effect of unilateral phrenectomy on rat of protein synthesis in rat diaphragm in vivo. Biochim Biophys Acta 349:109–113

    PubMed  CAS  Google Scholar 

  • Waterlow JC, Garlick PJ, Millward DJ (1978) Protein turnover in mammalian tissues and the whole body. North-Holland, New York, p 543

    Google Scholar 

  • Young VR (1970) The role of skeletal and cardiac muscle in the regulation of protein metabolism. In: Munro HM (ed) Mammalian protein metabolism IV. Academic Press, New York, pp 586–674

    Google Scholar 

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This research was supported in part by the Muscular Dystrophy Association

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Little, B.W., Barlow, R. & Perl, D.P. Denervation modulated changes in mouse skeletal muscle RNA concentration. Virchows Archiv B Cell Pathol 39, 1–7 (1982). https://doi.org/10.1007/BF02892831

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  • DOI: https://doi.org/10.1007/BF02892831

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