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The fate of desmin and titin during the degeneration and regeneration of the soleus muscle of the rat

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Summary

We studied the fate of desmin and titin in rat skeletal muscle during a cycle of degeneration and regeneration induced in vivo by the inoculation of a snake venom. Cryosections of muscle were labelled using antibodies to the two proteins, and examined at fixed time points after venom injection. Early pathological changes in the muscle, such as hypercontraction, preceded the loss of desmin. Immunolabelling using anti-desmin antibodies showed that desmin bridges were still intact when adjacent myofibrils were no longer aligned. The results suggested that although the hydrolysis of desmin is not necessary for the hypercontraction of muscle fibres, it probably contributes to complete fibre breakdown. Titin, or at least the part which lies close to the M-line, remained intact longer than desmin, but was also hydrolysed prior to complete disintegration of the fibres. Both desmin and titin were re-expressed in the regenerating myotubes by 2 days after venom inoculation, and became well organised even before the myofibrils became aligned. We conclude that desmin and titin are involved in both establishing and maintaining the structural integrity of the muscle fibres.

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References

  1. Bornemann A, Schmalbruch H (1992) Desmin and vimentin in regenerating muscles. Muscle Nerve 15:14–20

    Google Scholar 

  2. Bullard B, Sainsbury G, Miller N (1990) Digestion of proteins associated with Z-discs by calpain. J Muscle Res Cell Motil 11:271–279

    Google Scholar 

  3. Cullen MJ, Fulthorpe JJ, Harris JB (1992) The distribution of desmin and titin in normal and dystrophic (Xp-21) human muscle. Acta Neuropathol 83:158–169

    Google Scholar 

  4. Fürst DO, Osborn M, Nave R, Weber K (1988) The organisation of titin filaments in the half sarcomere revealed by monoclonal antibodies in immunoelectron microscopy: a map of ten non-repetitive epitopes starting at the Z-line extends close to the M-line. J Cell Biol 106:1563–1572

    Google Scholar 

  5. Fürst DO, Osborn M, Weber K (1989) Myogenesis in the mouse embryo: differential onset of expression of myogenic proteins and the involvement of titin in myofibril assembly. J Cell Biol 109:517–527

    Google Scholar 

  6. Gard DL, Lazarides E (1980) The synthesis and distribution of desmin and vimentin during myogenesis in vitro. Cell 19:263–275

    Google Scholar 

  7. Geiger B (1987) Intermediate filaments: looking for a function. Nature 329:392–393

    Google Scholar 

  8. Grubb BD, Harris JB, Schofield IS (1991) Neuromuscular transmission at newly formed neuromuscular junctions in the regenerating soleus muscle of the rat. J Physiol (Lond) 441:405–421

    Google Scholar 

  9. Gutierrez JM, Arce V, Brenes F, Chaves F (1990) Changes in myofibrillar components after skeletal muscle necrosis induced by a myotoxin isolated from the venom of the snake Bothrops asper. Exp Mol Pathol 52:25–36

    Google Scholar 

  10. Harris JB (1984) Polypeptides from snake venoms which act on nerve and muscle. In: Ellis GP, West GB (eds) Progress in medicinal chemistry. Elsevier Science Publishers, Amsterdam, p 95

    Google Scholar 

  11. Harris JB, Cullen MJ (1990) Muscle necrosis caused by snake venoms and toxins. Electron Microsc Rev 3:183–211

    Google Scholar 

  12. Harris JB, Johnson MA (1978) Further observations on the pathological responses of rat skeletal muscle to toxins isolated from the venom of the Australian tiger snake, Notechis scutatus scutatus. Clin Exp Pharmacol Physiol 5:587–600

    Google Scholar 

  13. Harris JB, MacDonell CA (1981) Phospholipase A2 activity of notexin and its role in muscle damage. Toxicon 19:419–430

    Google Scholar 

  14. Harris JB, Johnson MA, Karlsson E (1975) Pathological response of rat skeletal muscle to a single subcutaneous injection of a toxin, isolated from the venom of the Australian tiger snake, Notechis scutatus scutatus. Clin Exp Pharmacol Physiol 2:282–404

    Google Scholar 

  15. Horowitz R, Podolsky RJ (1987) The positional stability of thick filaments in activated skeletal muscle depends on sarcomere length: evidence for the role of titin filaments. J Cell Biol 105:2217–2223

    Google Scholar 

  16. Horowitz R, Kempner ES, Bisher ME, Podolsky PJ (1986) A physiological role for titin and nebulin in skeletal muscle. Nature 323:160–164

    CAS  PubMed  Google Scholar 

  17. Isaacs WB, Kim IS, Struve A, Fulton AB (1989) Biosynthesis of titin in cultured skeletal muscle cells. J Cell Biol 109:2189–2195

    Google Scholar 

  18. Itoh Y, Suzuki T, Kimura S, Ohashi K, Higuchi H, Sawada H, Shimizu T, Shibata M, Maruyama K (1988) Extensible and less-extensible domains of connectin filaments in stretched vertebrate skeletal muscle sarcomeres as detected by immunofluorescence and immunoelectron microscopy using monoclonal antibodies. J Biochem 104:504–508

    Google Scholar 

  19. Komiyama M, Maruyama K, Shimada Y (1990) Assembly of connectin (titin) in relation to myosin and α-actinin in cultured cardiac myocytes. J Muscle Res Cell Motil 11:419–428

    Google Scholar 

  20. Lazarides E (1980) Intermediate filaments as mechanical integrators of cellular space. Nature 283:249–256

    Google Scholar 

  21. Lilienbaum A, Li Z, Butler-Browne G, Bolmont C, Grimaud JA, Paulin D (1988) Human desmin gene: utilisation as a marker of human muscle differentiation. Cell Mol Biol 34:663–672

    Google Scholar 

  22. Maltin CA, Harris JB, Cullen MJ (1983) Regeneration of mammalian skeletal muscle following the injection of the snake-venom toxin, taipoxin. Cell Tissue Res 232:565–577

    Google Scholar 

  23. Maruyama K, Yoshioka T, Higuchi H, Kimura S, Natori R (1985) Connectin filaments link thick filaments and Z-lines in frog skeletal muscle as revealed by immunoelectron microscopy. J Cell Biol 101:2167–2172

    Google Scholar 

  24. Maruyama K, Matsuno A, Higuchi H, Shimaoka S, Kimura S, Shimizu T (1989). Behaviour of connectin (titin) and nebulin in skinned muscle fibres released after extreme stretch as revealed by immunoelectron microscopy. J Muscle Res Cell Motil 10:350–359

    Google Scholar 

  25. Matsumura K, Shimizu T, Nonaka I, Mannen T (1989) Immunochemical study of connectin (titin) in neuromuscular diseases using a monoclonal antibody: connectin is degraded extensively in Duchenne muscular dystrophy. J Neurol Sci 93:147–156

    Google Scholar 

  26. Nicholson LVB, Davison K, Falkous G, Harwood C, O'Donnell E, Slater CR, Harris JB (1989) Dystrophin in skeletal muscle. I. Western blot analysis using a monoclonal antibody. J Neurol Sci 94:125–136

    Google Scholar 

  27. Schultheiss T, Lin Z, Ishikawa H, Zamir I, Stoeckert CJ, Holtzer H (1991) Desmin/vimentin intermediate filaments are dispensable for many aspects of myogenesis. J Cell Biol 114:953–966

    Google Scholar 

  28. Sewry CA, Dubowitz V (1988) Histochemical and immunocytochemical studies in neuromuscular diseases. In: Walton JL (ed) Disorders of Voluntary Muscle, 5th edn. Churchill Livingstone, Edinburgh, pp 241–283

    Google Scholar 

  29. Shoeman RL, Traub P (1990) Calpains and the cytoskeleton. In: Mellgren RL, Murachi T (eds) Intracellular calcium-dependent proteolysis. CRC Press, Boca Raton, pp 191–209

    Google Scholar 

  30. Thornell L-E, Edstrom L, Eriksson A, Henriksson K-G, Angqvist K-A (1980) The distribution of intermediate filament protein (skeletin) in normal and diseased human skeletal muscle. J Neurol Sci 47:153–170

    Google Scholar 

  31. Tokuyasu KT, Dutton AH, Singer SJ (1983) Immunoelectron microscopic studies of desmin (skeletin) localisation and intermediate filament organisation in chicken skeletal muscle. J Cell Biol 96:1727–1735

    Google Scholar 

  32. Tokuyasu KT, Maher PA, Singer SJ (1984) Distributions of vimentin and desmin in developing chick myotubes in vivo. I. Immunofluorescence study. J Cell Biol 98:1961–1972

    Google Scholar 

  33. Tokuyasu KT, Maher PA, Singer SJ (1985) Distributions of vimentin and desmin in developing chick myotubes in vivo. II. Imunoelectron microscopic study. J Cell Biol 100:1157–1166

    Google Scholar 

  34. Traub P (1985) Intermediate filaments. In: Intermediate filaments. A review. Springer-Verlag, Berlin Heidelberg New York Tokyo

    Google Scholar 

  35. Trinick J, Knight P, Whiting A (1984) Purification and properties of native titin. J Mol Biol 180:331–356

    Google Scholar 

  36. Vater R, Cullen MJ, Harris JB, Nicholson LVB (1992) The fate of dystrophin during the degeneration and regeneration of the soleus muscle of the rat. Acta Neuropathol 83:140–148

    Google Scholar 

  37. Wang K, Wright J (1988) Architecture of the sarcomere matrix of skeletal muscle: immunoelectron microscopic evidence that suggests a set of parallel inextensible nebulin filaments anchored at the Z-line. J Cell Biol 107:2199–2212

    Google Scholar 

  38. Wang K, Ramirez-Mitchell R, Palter D (1984) Titin in an extraordinarily long, flexible and slender myofibrillar protein. Proc Natl Acad Sci USA 81:3685–3689

    Google Scholar 

  39. Wang K, Wright J, Ramirez-Mitchell R (1985) Architecture of the titin/nebulin containing cytoskeletal lattice of the striated muscle sarcomere: evidence of elastic and inelastic domains of the bipolar filaments. Biophys J 47:349a

    Google Scholar 

  40. Watkins SC, Samuel JL, Marotte F, Bertier-Savalle B, Rappaport L (1987) Microtubules and desmin filaments during onset of heart hypertrophy in rat: a double immunoelectron microscope study. Circ Res 60:327–336

    Google Scholar 

  41. Whiting A, Wardale J, Trinick J (1989) Does titin regulate the length of muscle thick filaments? J Mol Biol 205:263–268

    Google Scholar 

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Authors and Affiliations

  1. Muscular Dystrophy Group Research Laboratories, Regional Neurosciences Centre, Newcastle General Hospital, Westgate Road, NE4 6BE, Newcastle-upon-Tyne, UK

    R. Vater, M. J. Cullen & J. B. Harris

Authors
  1. R. Vater
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  2. M. J. Cullen
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  3. J. B. Harris
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Supported by the Muscular Dystrophy Group of Great Britain, the Wellcome Trust and the MRC

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Vater, R., Cullen, M.J. & Harris, J.B. The fate of desmin and titin during the degeneration and regeneration of the soleus muscle of the rat. Acta Neuropathol 84, 278–288 (1992). https://doi.org/10.1007/BF00227821

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  • DOI: https://doi.org/10.1007/BF00227821

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