Skip to main content

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 446))

Abstract

Studies in our laboratory indicate that extracellular ATP (ATP)0 may induce cell death by reactive oxygen insults. We have also shown that the Ca2+-induced oxidative stress as elicited by ATP may lead to an activation of a specific AP-1 activity. Since early impairment of mitochondria constitutes a critical event of the apoptotic cell death, we have examined whether (ATP)o will affect mitochondrial damage and cell injury by using mitochondrial specific probes, dihydrorhodamine and 3-(4,5-dimethylthiazo-2-yl)-2,5-diphenyl tetrazolium bromide (MTT). We have found that (ATP)o induced cell death in a concentration dependent manner by MTT assay. The (ATP)o induced cell death correlated well with the reactive oxygen species (ROS) generation in mitochondria, since (ATP)o enhanced both cell death and ROS production and antioxidant blocked both of these processes. We found (ATP)O treatment led to apoptotic cell death by examining DNA laddering and the TUNEL assay. Interestingly, vitamin C and vitamin E combined treatment appeared to attenuate the (ATP)o-induced apoptosis. Results indicated that (ATP)o may cause oxidative damage of mitochondria leading to apoptotic cell death. Antioxidants may be useful in preventing apoptosis by preventing ROS formation in mitochondria.

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 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
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

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Similar content being viewed by others

References

  • Bean B.P. (1992) Pharmacology and electrophysiology of ATP-activated ion channels. Trends Pharmacol. Sci. 13, 87–90.

    Article  PubMed  CAS  Google Scholar 

  • Burkitt M.J. and Gilbert B.C. (1990) Model studies of the iron-catalysed Haber-Weiss cycle and the ascorbatedriven Fenton reaction. Free Radie. Res. Commun. 10, 265–280.

    Article  CAS  Google Scholar 

  • Burnstock G. (1986) The changing face of autonomie transmission. Acta Physiol. Scand. 126, 76–91.

    Article  Google Scholar 

  • Buttke T.M. and Sandstrom P.A. (1994) Oxidative stress as a mediator of apoptosis. Immunol. Today 15, 7–10.

    Article  PubMed  CAS  Google Scholar 

  • Chanvitayapongs S., Draczynska-Lusiak B. and Sun A.Y. (1997) Amelioration of oxidative stress by antioxidants and resveratrol in PC12 cells. NeuroReport 8, 1499–1502.

    Article  PubMed  CAS  Google Scholar 

  • Chen W., Wieraszko A., Hogan M.V., Yan H.A., Kornecki E. and Ehrlich Y.H. (1996) Surface protein phosphorylation by ecto-protein kinase is required for the maintenance of hippocampal long-term potentiation. Proc. Nail. Acad. Sci. USA 93, 8688–8693.

    Article  CAS  Google Scholar 

  • Chen Y. and Sun A.Y. (1997) Activation of transcription factor AP-1 by extracellular ATP in PC 12 cells. Neurochem. Res. (In press).

    Google Scholar 

  • Cheng Y., Wixom P., James-Kracke M.R. and Sun A.Y. (1994) Effects of extracellular ATP on Fe2--induced cyto-toxicity in PC 12 cells. J. Neurochem. 63, 895–902.

    Article  PubMed  CAS  Google Scholar 

  • Cheng Y, Chen M., James-Kracke M.R., Wixom P. and Sun A.Y. (1996) Enhanced lipid peroxidation by extracellular ATP in PC12 cells. Neurochem. Res. 21, 27–33.

    Article  PubMed  CAS  Google Scholar 

  • Chernyak B.V. (1997) Redox regulation of the mitochondrial permeability transition pore. Biosci. Reports 17, 293–302.

    Article  CAS  Google Scholar 

  • Draczynska-Lusiak B., Chen Y.M. and Sun A.Y. (1997) Oxidized lipoproteins activate NF-KB binding activity and apoptosis in PC 12 cells. NeuroReport (In press).

    Google Scholar 

  • Du Y.S., Dodel R.C., Bales K.R., Jemmerson R., Hamiltonbyrd E. and Paul S.M. (1997) Involvement of a caspase 3-like cysteine protease in l-methyl-4-phenylpyridinium-mediated apoptosis of cultured cerebellar granule neurons. J. Neurochem. 69, 1382–1388.

    Article  PubMed  CAS  Google Scholar 

  • Emmendorffer A., Hecht M., Lohmann-Matthes M.-L. and Roesler J. (1990) A fast and easy method to determine the production of reactive oxygen intermediates by human and murine phagocytes using dihydrorhodamine 123. J. Immunol. Methods 131, 269–275.

    Article  PubMed  CAS  Google Scholar 

  • Francelanord V., Brugg B., Michel P.P., Agid Y and Ruberg M. (1997) Mitochondrial free radical signal in ceramide-dependent apoptosis — a putative mechanism for neuronal death in Parkinson’s disease. J. Neurochem. 69, 1612–1621.

    Article  CAS  Google Scholar 

  • Gavrieli Y, Sherman Y. and Ben-Sasson S.A. (1992) Identification of programmed cell death in situ via specific labeling of nuclear fragmentation. J. Cell Biol. 119, 493–501.

    Article  PubMed  CAS  Google Scholar 

  • Hendley E.D., Whittemore S.R., Chaffee J.E. and Ehrlich Y.H. (1988) Regulation of norepinephrine uptake by adenine nucleotides and divalent cations: role for extracellular protein phosphorylation. J. Neurochem. 50, 263–273.

    Article  PubMed  CAS  Google Scholar 

  • Hirsch T., Marzo T. and Kroemer G. (1997) Role of the mitochondrial permeability transition pore in apoptosis. Biosci. Reports 17, 67–76.

    Article  CAS  Google Scholar 

  • Hogan M.V., Pawlowska Z., Yang H.-A., Kornecki, E. and Ehrlich Y.H. (1995) Surface phosphorylation by ecto-protein kinase C in brain neurons. A target for Alzheimer’s ß-amyloid peptide. J. Neurochem. 65, 2022–2030.

    Article  PubMed  CAS  Google Scholar 

  • Illes P. and Norenberg W. (1993) Neuronal ATP receptors and their mechanism of action. Trends Pharmacol. Sci. 14, 50–54.

    Article  PubMed  CAS  Google Scholar 

  • Inoue K., Nakasawa K., Fujimori K., Watano T. and Takanaka A. (1992) Extracellular adenosine 5′-triphosphate-evoked glutamate release in cultured hippocampal neurons. Neurosci. Lett. 134, 215–218.

    Article  PubMed  CAS  Google Scholar 

  • Jahr C.E. and Jessell T.M. (1983) ATP excites a population of rat dorsal horn neurones. Nature 304, 730–733.

    Article  PubMed  CAS  Google Scholar 

  • Kornecki E. and Ehrlich Y. (1991) Calcium ion mobilization in neuronal cells induced by PAF. Lipids 26, 1243–1246.

    Article  PubMed  CAS  Google Scholar 

  • Krishtal O.A., Marchenko S.M. and Obukhov A.G. (1988) Cationic channels activated by extracellular ATP in rat sensory neurons. Neuroscience 27, 995–1000.

    Article  PubMed  CAS  Google Scholar 

  • Li W.P., Chan W.Y., Lai H.W.L. and Yew D.T. (1997) Terminal dUTP nick end labeling (TUNEL) positive cells in the different regions of the brain in normal and Alzheimer’s patients. J. Mol. Neurosci. 8, 75–82.

    Article  PubMed  CAS  Google Scholar 

  • Lin S.-H. (1989) Localization of the ecto-ATPase (Ecto-nucleotidase) in the rat hepatocyte plasma membrane. J. Biol. Chem. 264, 14402–14407.

    Google Scholar 

  • Lyons A.B., Samuel K., Sanderson A. and Meddy A.H. (1992) Simultaneous analysis of immunophenotype and apoptosis of murine thymocytes by single laser flow cytometry. Cytometry 13:809–821.

    Article  PubMed  CAS  Google Scholar 

  • Lyras L., Cairns N.J., Jenner A., Jenner P. and Halliwell B. (1997) An assessment of oxidative damage to proteins, lipids and DNA in brain from patients with Alzheimer’s disease. J. Neurochem. 68, 2061–2069.

    Article  PubMed  CAS  Google Scholar 

  • McCord J.M. (1987) Oxygen-derived radicals: a link between reperfusion injury and inflammation. Fed. Proc. 46, 2402–2406.

    PubMed  CAS  Google Scholar 

  • Nicotera P., Bellomo G. and Orrenius S. (1992) Calcium-mediated mechanisms in chemically induced cell death. Annu. Rev. Pharmacol. Toxicol. 32, 449–470.

    Article  PubMed  CAS  Google Scholar 

  • Olanow C.W. (1992) An introduction of the free radical hypothesis in Parkinson’s disease. Ann. Neurol. 32(Suppl.), S2–S9.

    Article  PubMed  CAS  Google Scholar 

  • Petit P.X., Zamzami N., Vayssiere J.L., Mignotte B., Kroemer G. and Castedo M. (1997) Implication of mitochondria in apoptosis. Mol. Cell. Biochem. 174, 185–188.

    Article  PubMed  CAS  Google Scholar 

  • Richardson P.J. and Brown S.J. (1989) ATP release from affinity purified rat cholinergic nerve terminals. J. Neurochem. 48. 622–630.

    Article  Google Scholar 

  • Rothe G., Oser A. and Valet G. (1988) Dihydrorhodamine 123: a new flow cytometric indicator for respiratory burst activity in neutrophil granulocytes. Naturwissenschaftern 75, 354.

    Article  CAS  Google Scholar 

  • Sayre L.M., Zalasko D.A., Harris P.L.R., Perry G., Salomon R.G. and Smith M.A. (1997) 4-hydroxynonenal-derived advanced lipid peroxidation end product are increased in Alzheimer’s disease. J. Neurochem. 68, 2092–2097.

    Article  PubMed  CAS  Google Scholar 

  • Valera S., Hussy N., Evans R.J., Aclamp N., North R.A., Surprenant A. and Buell G. (1994) Anew class of ligandgated ion channel defined by P2x receptor for extracellular ATP. Nature 371, 516–527.

    Article  PubMed  CAS  Google Scholar 

  • Von Kugelgen I. and Starke K. (1994) Co-release of noradrenaline and ATP by brief pulse trains in guinea pig vas deferens. Naunyn-Schmiedeberg Arch. Pharmacol. 350, 123–129.

    Article  CAS  Google Scholar 

  • Von Kugelgen I., Allgaier C., Schubert A. and Starke K. (1994) Co-release of noradrenaline and ATP from cultured sympathetic neurons. Neuroscience 61, 199–202.

    Article  Google Scholar 

  • Wang K.W. and Yuen P.W. (1994) Calpain inhibition: An overview of its therapeutic potential. TIPS. 15. 412–419.

    PubMed  CAS  Google Scholar 

  • Wixom P.M. and Sun A.Y. (1988) Effect of ethanol on Ca2+ dependent phosphorylation of a 45 kDa synaptosomal protein, in Biomedical and Social Aspects of Alcohol and Alcoholism (Kuriyama K., Takada A. and Ishii H.. eds), pp311–314, Excerpta Medica, Amsterdam.

    Google Scholar 

  • Zimmerman H., Dawdall M.J. and Lane D.A. (1979) Purine salvage at the cholinergic nerve endings of the Torpedo electric organ: the central role of adenosine. Neuroscience 4, 979–993.

    Article  Google Scholar 

  • Zimmermann H. (1994) Signalling via ATP in the nervous system. TINS. 17, 420–426.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1998 Springer Science+Business Media New York

About this chapter

Cite this chapter

Sun, A.Y., Chen, YM. (1998). Extracellular ATP-Induced Apoptosis in PC12 Cells. In: Ehrlich, Y.H. (eds) Molecular and Cellular Mechanisms of Neuronal Plasticity. Advances in Experimental Medicine and Biology, vol 446. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4869-0_5

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-4869-0_5

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7209-7

  • Online ISBN: 978-1-4615-4869-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics