Skip to main content

Advertisement

Log in

Involvement of CAPON and Nitric Oxide Synthases in Rat Muscle Regeneration After Peripheral Nerve Injury

  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

Carboxy-terminal PDZ ligand of nNOS (CAPON) protein, as an adaptor, binds to nNOS via the PDZ domain helping regulate neuronal nitric oxide synthase (nNOS) activity at post-synaptic sites in neurons (Jaffrey et al., Neuron, 20, 115–124, 1998). Recently, it has been reported that CAPON is present in mouse muscle and may be involved in mouse muscle growth, injury, and repair possibly by regulating the stability, activity, or position of nNOS (Segalat et al., Experimental Cell Research, 302, 170–179, 2005). The present study was to explore the expression patterns and roles of CAPON as well as NOS in rat muscle regeneration after nerve injury. Normal Sprague–Dawley rats were subjected to right sciatic nerve crush injury. Walking track analysis, real time polymerase chain reaction, Western blotting, in situ hybridization, immunocytochemistry, and co-immunoprecipitation techniques were used. It revealed that CAPON mRNA increased, which peaked on days 1 and 28, whereas nNOS mRNA underwent a downregulation in the ipsilateral gastrocnemius muscles after sciatic nerve injury. Their proteins approximately paralleled the mRNA expression. CAPON and nNOS were identified in the activated satellite cells or myotubes and their in vivo interaction was verified. However, eNOS and iNOS proteins suffered an upregulation and were detected in activated satellite cells or myotubes. These data suggest that CAPON and all these three isoforms of NOS might be involved in muscle regeneration after nerve injury. Further study is necessary for a better understanding of the potential functional link between CAPON, NOS, and muscle regeneration, with possible application to therapy for skeletal muscle repair from nerve injury.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

References

  • Alderton, W. K., Cooper, C. E., & Knowles, R. G. (2001). Nitric oxide synthases: Structure, function and inhibition. Biochemical Journal, 357, 593–615.

    Article  PubMed  CAS  Google Scholar 

  • Anderson, J. E. (2000). A role for nitric oxide in muscle repair: Nitric oxide-mediated satellite cell activation. Molecular Biology of the Cell, 11, 1859–1874.

    PubMed  CAS  Google Scholar 

  • Anderson, J. E., & Pilipowicz, O. (2002). Activation of muscle satellite cells in single fiber cultures. Nitric Oxide: Biology and Chemistry, 7, 36–41.

    Article  CAS  Google Scholar 

  • Anderson, J. E., & Vargas, C. (2003). Correlated NOS-Iμ and Myf-5 expression by satellite cells in mdx mouse muscle regeneration during NOS manipulation and deflazacort treatment. Neuromuscular Disorders, 13, 388–396.

    Article  PubMed  Google Scholar 

  • Blottner, D., & Luck, G. (2001). Just in time and place: NOS/NO system assembly in neuromuscular junction formation. Microscopy Research and Technique, 55, 171–180.

    Article  PubMed  CAS  Google Scholar 

  • Christova, T., Grozdanovic, Z., & Gossrau, R. (1997). Nitric oxide synthase (NOS) I during postnatal development in rat and mouse skeletal muscle. Acta Histochemica, 99, 311–324.

    PubMed  CAS  Google Scholar 

  • Cohn, R. D., & Campbell, K. P. (2000). Molecular basis of muscular dystrophies. Muscle Nerve, 23, 1456–1471.

    Article  PubMed  CAS  Google Scholar 

  • Cooper, R. N., Tajbakhsh, S., Mouly, V., Cossu, G., Buckingham, M., & Butler-Browne, G. S. (1999). In vivo satellite cell activation via Myf-5 and MyoD in regenerating mouse skeletal muscle. Journal of Cell Science, 112, 2895–2901.

    PubMed  CAS  Google Scholar 

  • Dedio, J., KÖnig, P., Wohlfart, P., Schroeder, C., Kummer, W., & Müller-Esterl, W. (2001). NOSIP, a novel modulator of endothelial nitric oxide synthase activity. FASEB Journal, 15, 79–89.

    Article  PubMed  CAS  Google Scholar 

  • Denninger, J. W., & Marletta, M. A. (1999). Guanylate cyclase and the NO/cGMP signaling pathway. Biochimica Et Biophysica Acta, 1411, 334–350.

    Article  PubMed  CAS  Google Scholar 

  • Fang, M., Jaffrey, S. R., Sawa, A., Ye, K., Luo, X., & Snyder, S. H. (2000). Dexras1: A G protein specifically coupled to neuronal nitric oxide synthase via CAPON. Neuron, 28, 183–193.

    Article  PubMed  CAS  Google Scholar 

  • George, A., Buehl, A., & Sommer, C. (2004). Wallerian degeneration after crush injury of rat sciatic nerve increases endo- and epineurial tumor necrosis factor-alpha protein. Neuroscience Letters, 372, 215–219.

    Article  PubMed  CAS  Google Scholar 

  • Grozdanovic, Z., & Baumgarten, H. G. (1999). Nitric oxide synthase in skeletal muscle fibers: a signaling component of the dystrophin-glycoprotein complex. Histology and Histopathology, 14, 243–256.

    PubMed  CAS  Google Scholar 

  • Jaffrey, S. R., Benfenati, F., Snowman, A. M., Czernik, A. J., & Snyder, S. H. (2001). Neuronal nitric-oxide synthase localization mediated by a ternary complex with synapsin and CAPON. Proceedings of the National Academy of Sciences of the United States of America, 99, 3199–3204.

    Article  Google Scholar 

  • Jaffrey, S. R., Snowman, A. M., Eliasson, M. J. L., Cohen, N. A., & Snyder, S. H. (1998). CAPON: A protein associated with neuronal nitric oxide synthase that regulates its interactions with PSD95. Neuron, 20, 115–124.

    Article  PubMed  CAS  Google Scholar 

  • Kablar, B., Krastel, K., Tajbakhsh, S., & Rudnicki, M. A. (2003). Myf-5 and MyoD activation define independent myogenic compartments during embryonic development. Developments in Biologicals, 258, 307–318.

    Article  CAS  Google Scholar 

  • Lu, J., Moochhala, S., Shirhan, M., Ng, K. C., Tan, M. H., Teo, A. L., & Ling, E. A. (2003). Nitric oxide induces macrophage apoptosis following traumatic brain injury in rats. Neuroscience Letters, 339, 147–150.

    Article  PubMed  CAS  Google Scholar 

  • Luck, G., Hoch, W., Hopf, C., & Blottner, D. (2000). Nitric oxide synthase (NOS-1) coclustered with agrin-induced AChR-specializations on cultured skeletal myotubes. Molecular and Cellular Neurosciences, 16, 269–281

    Article  PubMed  CAS  Google Scholar 

  • Predescu, D., Predescu, S., Shimizu, J., Miyawaki-Shimizu, K., & Malik, A. B. (2005). Constitutive eNOS-derived nitric oxide is a determinant of endothelial junctional integrity. American Journal of Physiology. Lung Cellular and Molecular Physiology, 289, L371–L381.

    Article  PubMed  CAS  Google Scholar 

  • Reid, M. B. (1998). Role of nitric oxide in skeletal muscle: synthesis, distribution and functional importance. Acta Physiologica Scandinavica, 162, 401–409.

    Article  PubMed  CAS  Google Scholar 

  • Sabourin, L. A., & Rudnicki, M. A. (2000). The molecular regulation of myogenesis. Clinical Genetics, 57, 16–25.

    Article  PubMed  CAS  Google Scholar 

  • Satake, K., Matsuyama, Y., Kamiya, M., Kawakami, H., Iwata, H., Adachi, K., & Kiuchi, K. (2000). Nitric oxide via macrophage iNOS induces apoptosis following traumatic spinal cord injury. Brain Research. Molecular Brain Research, 85, 114–122.

    Article  PubMed  CAS  Google Scholar 

  • Segalat, L., Grisoni, K., Archer, J., Vagas, C., Bertrand, A., & Anderson, J. E. (2005). CAPON expression in skeletal muscle is regulated by position, repair, NOS activity, and dystrophy. Experimental Cell Research, 302, 170–179.

    Article  PubMed  CAS  Google Scholar 

  • Shen, A., Zhu, D., Ding, F., Zhu, M., Gu, X., & Gu, J. (2003). Increased gene expression of β-1, 4-galactosyltransferase I in rat injured sciatic nerve. Journal of Molecular Neuroscience, 21, 103–110.

    Article  PubMed  CAS  Google Scholar 

  • Shen, A., Wang, H., Zhang, Y., Yan, J., Zhu, D., & Gu, J. (2002). Expression of β-1, 4-galactosyltransferase II and V in rat injured sciatic nerves. Neuroscience Letters, 327, 45–48.

    Article  PubMed  CAS  Google Scholar 

  • Silvagno, F., Xia, H., & Bredt, D. S. (1996). Neuronal nitric-oxide-μ, an alternatively spliced isoform expressed in differentiated skeletal muscle. Journal of Biological Chemistry, 271, 11204–11208.

    Article  PubMed  CAS  Google Scholar 

  • Tatsumi, R., Hattori, A., Ikeuchi, Y., Anderson, J. E., & Allen, R. E. (2002). Release of hepatocyte growth factor from mechanically stretched skeletal muscle satellite cells and the role of pH and nitric oxide. Molecular Biology of the Cell, 13, 2909–2918.

    Article  PubMed  CAS  Google Scholar 

  • Tews, D. S., Goebel, H. H., Schneider, I., Gunkel, A., Stennert, E., & Neiss, W. F. (1997). Expression of different isoforms of nitric oxide synthase in experimentally denervated and reinnervated skeletal muscle. Journal of Neuropathology and Experimental Neurology, 56, 1283–1289.

    PubMed  CAS  Google Scholar 

  • Wang, Y., Newton, D. C., & Marsden, P. A. (1999). Neuronal NOS: Gene structure, mRNA diversity, and functional relevance. Critical Reviews in Neurobiology, 13, 21–43.

    PubMed  Google Scholar 

  • Wehling, M., Spencer, M. J., & Tidball, J. G. (2001). A nitric oxide synthase transgene ameliorates muscular dystrophy in mdx mice. Journal of Cell Biology, 155, 123–131.

    Article  PubMed  CAS  Google Scholar 

  • Wozniak, A. C., Kong, J., Bock, E., Pilipowicz, O., & Aderson, J. E. (2005). Signaling satellite-cell activation in skeletal muscle: Markers, models, stretch, and potential alternate pathways. Muscle Nerve, 31, 283–300.

    Article  PubMed  CAS  Google Scholar 

  • Zimmermann, K., Opitz, N., Dedio, J., Renne, C., Müller-Esterl, W., & Oess, S. (2002). NOSTRIN: a protein modulating nitric oxide release and subcellular distribution of endothelial nitric oxide synthase. Proceedings of the National Academy of Sciences of the United States of America, 99, 17167–17172.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work is supported by Nature Science Foundation of China (30300099, 30770488), Jiangsu Province Natural Scientific Grants (BK2003035) and the Grant of the Jiangsu Province Key Lab of Neuroregeneration.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Aiguo Shen.

Additional information

M. Chen and C. Cheng contribute equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chen, M., Cheng, C., Yan, M. et al. Involvement of CAPON and Nitric Oxide Synthases in Rat Muscle Regeneration After Peripheral Nerve Injury. J Mol Neurosci 34, 89–100 (2008). https://doi.org/10.1007/s12031-007-9005-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12031-007-9005-y

Keywords

Navigation