Skip to main content

Nipradilol Promotes Axon Regeneration Through S-Nitrosylation of PTEN in Retinal Ganglion Cells

  • Conference paper
  • First Online:
Retinal Degenerative Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 801))

Abstract

Nipradilol (Nip) is registered as an anti-glaucoma agent. More recently, a protective effect of Nip has been demonstrated in retinal ganglion cells (RGCs) mediated by S-nitrosylation of antioxidative-related Keap1 protein due to its nitric oxide (NO)-donating effect. It also has been reported that Nip promoted axon outgrowth in cat RGCs. However, the detailed mechanism remains unclear. NO physiologically regulates numerous cellular responses through S-nitrosylation of protein at cysteine residues. It has been reported that phosphatase and tensin homologue deleted on chromosome 10 (PTEN) deletion strongly showed axon regeneration after optic nerve injury. PTEN inactivation by S-nitrosylation results in the accumulation of phosphatidylinositol (3, 4, 5) triphosphate (PIP3) and the activation of Akt/mammalian target of rapamycin (mTOR) signaling. The ribosomal S6 kinase 1 (S6K) which can monitor as phospho-S6 (pS6) is one of major target of mTOR. In this study, we investigated the possibility that Nip can promote axon outgrowth in RGCs by Akt/mTOR signaling thorough S-nitrosylation of PTEN.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Adachi T, Hori S, Miyazaki K, Takahashi E, Nakagawa M, Udagawa A, Hayashi N, Aikawa N, Ogawa S (1995) Rapid increase in plasma nitrite concentration following intravenous administration of nipradilol. Eur J Pharmacol 286:201–204

    Article  PubMed  CAS  Google Scholar 

  2. Kou K, Ibengwe J, Suzuki H (1984) Effects of alpha-adrenoceptor antagonists on electrical and mechanical responses of the isolated dog mesenteric vein to perivascular nerve stimulation and exogenous noradrenaline. Naunyn Schmiedebergs Arch Pharmacol 326:7–13

    Article  PubMed  CAS  Google Scholar 

  3. Uchida Y, Nakamura M, Shimizu S, Shirasawa Y, Fujii M (1983) Vasoactive and beta-adrenoceptor blocking properties of 3,4-dihydro-8-(2-hydroxy-3-isopropylamino) propoxy-3-nitroxy-2H-1-benzopyran (K-351), a new antihypertensive agent. Arch Int Pharmacodyn Ther 262:132–149

    PubMed  CAS  Google Scholar 

  4. Numajiri N, Takasawa K, Nishiya T, Tanaka H, Ohno K, Hayakawa W, Asada M, Matsuda H, Azumi K, Kamata H, Nakamura T, Hara H, Minami M, Lipton SA, Uehara T (2011) On-off system for PI3-kinase-Akt signaling through S-nitrosylation of phosphatase with sequence homology to tensin (PTEN). Proc Natl Acad Sci USA 108:10349–10354

    Article  PubMed Central  PubMed  Google Scholar 

  5. Park KK, Liu K, Hu Y, Smith PD, Wang C, Cai B, Xu B, Connolly L, Kramvis I, Sahin M, He Z (2008) Promoting axon regeneration in the adult CNS by modulation of the PTEN/mTOR pathway. Science 322:963–966

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  6. Ganapathy PS, Dun Y, Ha Y, Duplantier J, Allen JB, Farooq A, Bozard BR, Smith SB (2010) Sensitivity of staurosporine-induced differentiated RGC-5 cells to homocysteine. Curr Eye Res 35:80–90

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  7. Koriyama Y, Takagi Y, Chiba K, Yamazaki M, Arai K, Matsukawa T, Suzuki H, Sugitani K, Kagechika H, Kato S (2011) Neuritogenic activity of a genipin derivative in retinal ganglion cells is mediated by retinoic acid receptor β expression through nitric oxide/S-nitrosylation signaling. J Neurochem 119:1232–1242

    Article  PubMed  CAS  Google Scholar 

  8. Jaffrey SR, Erdjument-Bromage H, Ferris CD, Tempst P, Snyder SH (2001) Protein S-nitrosylation: a physiological signal for neuronal nitric oxide. Nat Cell Biol 3:193–197

    Article  PubMed  CAS  Google Scholar 

  9. Koriyama Y, Ohno M, Kimura T, Kato S (2009) Neuroprotective effects of 5-S-GAD against oxidative stress-induced apoptosis in RGC-5 cells. Brain Res 1296:187–195

    Article  PubMed  CAS  Google Scholar 

  10. Koriyama Y, Kamiya M, Takadera T, Arai K, Sugitani K, Ogai K, Kato S (2012) Protective action of nipradilol mediated through S-nitrosylation of Keap1 and HO-1 induction in retinal ganglion cells. Neurochem Int 61:1242–1253

    Article  PubMed  CAS  Google Scholar 

  11. Nakazawa T, Tomita H, Yamaguchi K, Sato Y, Shimura M, Kuwahara S, Tamai M (2002) Neuroprotective effect of nipradilol on axotomized rat retinal ganglion cells. Curr Eye Res 24:114–122

    Article  PubMed  Google Scholar 

  12. Watanabe M, Tokita Y, Yata T (2006) Axonal regeneration of cat retinal ganglion cells is promoted by nipradilol, an anti-glaucoma drug. Neuroscience 140:517–528

    Article  PubMed  CAS  Google Scholar 

  13. Yata T, Nakamura M, Sagawa H, Tokita Y, Terasaki H, Watanabe M (2007) Survival and axonal regeneration of off-center retinal ganglion cells of adult cats are promoted with an anti-glaucoma drug, nipradilol, but not BDNF and CNTF. Neuroscience 148:53–64

    Article  PubMed  CAS  Google Scholar 

  14. Liu K, Lu Y, Lee JK, Samara R, Willenberg R, Sears-Kraxberger I, Tedeschi A, Park KK, Jin D, Cai B, Xu B, Connolly L, Steward O, Zheng B, He Z (2010) PTEN deletion enhances the regenerative ability of adult corticospinal neurons. Nat Neurosci 13:1075–1081

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  15. Pei DS, Sun YF, Song YJ (2009) S-nitrosylation of PTEN Invovled in ischemic brain injury in rat hippocampal CA1 region. Neurochem Res 34:1507–1512

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yoshiki Koriyama .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media, LLC

About this paper

Cite this paper

Koriyama, Y., Kamiya, M., Arai, K., Sugitani, K., Ogai, K., Kato, S. (2014). Nipradilol Promotes Axon Regeneration Through S-Nitrosylation of PTEN in Retinal Ganglion Cells. In: Ash, J., Grimm, C., Hollyfield, J., Anderson, R., LaVail, M., Bowes Rickman, C. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 801. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3209-8_94

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-3209-8_94

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4614-3208-1

  • Online ISBN: 978-1-4614-3209-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics