Display options
Share it on

Neurotox Res. 2000 Feb;1(3):171-9. doi: 10.1007/BF03033288.

Dopamine induces cell death, lipid peroxidation and DNA base damage in a catecholaminergic cell line derived from the central nervous system.

Neurotoxicity research

J M Masserano, I Baker, D Venable, L Gong, S J Zullo, C R Merril, R J Wyatt

Affiliations

  1. Neuropsychiatry Branch, Laboratory of Biochemical Genetics, National Institute of Mental Health, Bethesda, MD 20892-2668, USA. [email protected]

PMID: 12835100 DOI: 10.1007/BF03033288

Abstract

Dopamine can be autoxidized to superoxides and quinones. Superoxides can form hydroxyl radicals that are highly reactive with lipids, proteins and DNA leading to neuronal damage and cell death. We used a clonal catecholaminergic cell line (CATH.a) derived from the central nervous system to evaluate the effects of dopamine on cell death, lipid peroxidation and DNA base damage. Dopamine produces cell death in CATH.a cells and this is associated with an increase in annexin binding, which is an early indicator of apoptosis. Incubation of CATH.a cells with deferoximine, an iron chealator, partially antagonizes dopamine-induced cell death. In CATH.a cells, dopamine produces an increase in both lipid peroxidation, as measured by cis-parinaric acid fluorescence, and DNA oxidative base damage, as measured by 8-hydroxy-2'-deoxyguanosine formation. Cell death was inhibited 84-92% by the hydrophilic antioxidants, dithiothreitol, L-cysteine, and N-acetylcysteine. The lipophilic vitamins, retinol and vitamin E and the vitamin E analog, Trolox, inhibited dopamine-induced cell death by 18-33%. The lipophilic antioxidants probucol, propyl glycol and butylated hydroxyanisone had no inhibitory effect on dopamine-induced cell death. These data suggest that damage to DNA and lipids may be partially responsible for dopamine-induced cell death in CATH.a cells.

References

  1. J Neurochem. 1991 Apr;56(4):1441-4 - PubMed
  2. J Neurochem. 1995 Apr;64(4):1703-7 - PubMed
  3. Brain Res. 1997 Oct 31;773(1-2):76-81 - PubMed
  4. Free Radic Biol Med. 1997;23(5):783-92 - PubMed
  5. J Neurosci. 1993 Mar;13(3):1280-91 - PubMed
  6. Neuropharmacology. 1996 May;35(5):571-8 - PubMed
  7. FEBS Lett. 1990 May 7;264(1):145-8 - PubMed
  8. Cytometry. 1998 Jan 1;31(1):1-9 - PubMed
  9. Drug Alcohol Depend. 1997 Nov 25;48(2):105-11 - PubMed
  10. Blood. 1997 Feb 15;89(4):1121-32 - PubMed
  11. Biochem Cell Biol. 1997;75(4):337-49 - PubMed
  12. J Neurochem. 1989 Feb;52(2):381-9 - PubMed
  13. FASEB J. 1987 Nov;1(5):358-64 - PubMed
  14. J Neurochem. 1990 Oct;55(4):1327-39 - PubMed
  15. Radiat Res. 1996 May;145(5):523-31 - PubMed
  16. J Exp Med. 1995 Nov 1;182(5):1545-56 - PubMed
  17. Neuroreport. 1997 Apr 14;8(6):1337-40 - PubMed
  18. J Neurochem. 1998 Feb;70(2):501-8 - PubMed
  19. Mol Pharmacol. 1978 Jul;14(4):644-53 - PubMed
  20. J Neurochem. 1998 Nov;71(5):2034-40 - PubMed
  21. Pharmacol Toxicol. 1997 Feb;80(2):76-84 - PubMed
  22. Exp Neurol. 1996 Sep;141(1):32-9 - PubMed
  23. J Pharmacol Exp Ther. 1992 Sep;262(3):1274-83 - PubMed
  24. J Exp Med. 1995 Nov 1;182(5):1597-601 - PubMed
  25. Ann Neurol. 1998 Sep;44(3 Suppl 1):S72-84 - PubMed
  26. J Biol Chem. 1974 Apr 25;249(8):2447-52 - PubMed
  27. Mol Pharmacol. 1996 Nov;50(5):1309-15 - PubMed
  28. Exp Neurol. 1998 Jul;152(1):88-94 - PubMed
  29. Neurosci Lett. 1998 Jan 30;241(2-3):71-4 - PubMed
  30. Neurosci Lett. 1996 Mar 8;206(1):5-8 - PubMed
  31. Nucleic Acids Res. 1996 Apr 15;24(8):1389-94 - PubMed
  32. Mutat Res. 1992 Sep;275(3-6):331-42 - PubMed
  33. Brain Res. 1996 Aug 12;729(2):264-9 - PubMed
  34. J Biol Chem. 1997 Oct 10;272(41):25409-12 - PubMed
  35. Free Radic Biol Med. 1995 Aug;19(2):209-17 - PubMed
  36. J Neurochem. 1992 Jul;59(1):99-106 - PubMed

Publication Types