Skip to main content
Log in

Oxidized lipoproteins may play a role in neuronal cell death in Alzheimer disease

  • Original Articles
  • Published:
Molecular and Chemical Neuropathology

Abstract

Oxidative stress in the central nervous system (CNS) may cause oxidation of lipoprotein particles. The oxidized lipoproteins may damage cellular and subcellular membranes, leading to tissue injury and cell death. Human low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) are oxidized by transition metal ions, such as Cu2+. Using PC 12 cells, we tested the cytotoxicity of oxidized LDL and VLDL. Cell death was increased in a dose-dependent manner. Antioxidants added to the incubation medium, such as vitamins E or C, or resveratrol showed some protection. Results indicated that oxidized lipoproteins may serve as an oxidative stressor, which may initiate the neuronal cell death leading to the manifestation of Alzheimer disease (AD).

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.

Similar content being viewed by others

References

  • Arichi H., Kimura Y., Okuda H., Baba K., Kozawa M., and Arichi S. (1982) Effects of stilbene components of the roots of Polygonum cuspidatum Sieb. et Zucc. on lipid metabolism.Chem. Pharm. Bull. 30, 1766–1770.

    PubMed  CAS  Google Scholar 

  • Borovic S., Zarkovic N., Wildburger R., Tatzber F., and Jurin M. (1995) Post-traumatic differences in the titer of autoantibodies against oxidized low density lipoproteins (OLDL) in the sera of patients with bone fracture and traumatic brain injury.Periodicum Biol. 97, 209–293.

    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 

  • Cheng Y., Chen M., James-Kracke M., 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 

  • Chisolm G. M., Ma G., Irwin K. C., Martin L. L., Gundeson K. G., Linberg L. F., et al. (1994) 7β-Hydroxy-peroxycholest-5-en-3β-ol, a component of human atherosclerotic lesions, is the primary cytotoxin of oxidized human low density lipoprotein.Proc. Natl. Acad. Sci. USA 91, 11,452–11,456.

    Article  CAS  Google Scholar 

  • Chung M. I., Teng C. M., Cheng K. L., Ko F. N., and Lin C. N. (1992) An anti-platelet principle of veratrum formosanum.Planta Med. 58, 274–276.

    Article  PubMed  CAS  Google Scholar 

  • Dehouck B., Dehouck M., Fruchart J., and Cecchelli R. (1994) Upregulation of the low density lipoprotein’s receptor at the blood-brain barrier: Intercommunications between brain capillary endothelial cells and astrocytes.J. Cell Biol. 126, 465–473.

    Article  PubMed  CAS  Google Scholar 

  • Dehouck B., Fenart L., Dehouck M., Pierce A., Tarpier G., and Cecchelli R. (1997) A new function for the LDL receptor: Transcytosis of LDL across the blood-brain barrier.J. Cell Biol. 138, 877–889.

    Article  PubMed  CAS  Google Scholar 

  • Escargueil-Blanc I., Salvayre R., and Negre-Salvayre A. (1994) Necrosis and apoptosis induced by oxidized low density lipoproteins occurs through two calcium-dependent pathways in lymphoblastoid cells.FASEB J. 8, 1075–1080.

    PubMed  CAS  Google Scholar 

  • Esterbauer H., Gebicki J., Puhl H., and Jürgens G. (1992) The role of lipid peroxidation and antioxidants in oxidative modification of LDL.Free Radical. Biol. Med. 13, 341–390.

    Article  CAS  Google Scholar 

  • Frankel E. N., Waterhouse A. L., and Kinsella J. E. (1993) Inhibition of human low density lipoprotein oxidation by resveratrol.Lancet 341, 1103, 1104.

    Article  PubMed  CAS  Google Scholar 

  • Goldstein J. L., Ho Y. K., Basu S. K., and Brown M. S. (1979) Binding site on macrophages that mediates uptake and degradation of acetylated LDL, producing massive cholesterol deposition.Proc. Natl. Acad. Sci. USA 96, 333–337.

    Article  Google Scholar 

  • Goldstein J. L., Basu S. K., and Brown M. S. (1983) Receptor mediated endocytosis of low-density lipoprotein in cultured cells.Methods Enzymol. 98, 241–261.

    Article  PubMed  CAS  Google Scholar 

  • Hatch F. T. and Lees R. S. (1968) Practical methods for plasma lipoproteins analysis.Adv. Lipid Res. 6, 1–68.

    PubMed  CAS  Google Scholar 

  • Hessler J. R., Robertson A. L., and Chisolm G. M. (1979) LDL-induced cytotoxicity and its inhibition by HDL in human vascular smooth muscle and endothelial cells in culture.Atherosclerosis 32, 213–229.

    Article  PubMed  CAS  Google Scholar 

  • Jang M., Cai L., Udeani G. O., Slowing K. V., Thomas C. F., Bescher C. W. W., et al. (1997) Cancer preventive activity of resveratrol, a natural product derived from grape.Science 275, 218–220.

    Article  PubMed  CAS  Google Scholar 

  • Kim D. H., Iijima H., Goto K., Sakai J., Ishii H., Kim H. J., et al. (1996) Human apolipoprotein E receptor 2. A novel lipoprotein receptor of the low density lipoprotein receptor family predominantly expressed in brain.J. Biol. Chem. 271, 8373–8380.

    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.

    PubMed  CAS  Google Scholar 

  • Osman I., Gaillard O., Meiller D., Bordas-Fonfrede M., Gervais A., Schuller E., et al. (1995) A sensitive time-resolved immunofluorometric assay for the measurement of apolipoprotein B in cerebrospinal fluid: application to multiple sclerosis and other neurological diseases.Eur. J. Clin. Chem. Clin. Biochem. 33, 53–58.

    PubMed  CAS  Google Scholar 

  • Pitas R. E., Boyles J. K., Lee S. H., Hui D., and Weisgraber K. H. (1987) Lipoproteins and their receptors in the central nervous system.J. Biol. Chem. 262, 14,352–14,360.

    CAS  Google Scholar 

  • Poirier J., Hess M., May P. C., and Finch C. E. (1991) Astrocytic apolipoprotein E mRNA and GFAP mRNA in hippocampus after entorhinal cortex lesioning.Mol. Brain Res. 11, 97–106.

    Article  PubMed  CAS  Google Scholar 

  • Poirier J., Baccichet A., Dea D., and Gauthier S. (1993) Cholesterol synthesis and lipoprotein reuptake during synaptic remodeling in hippocampus in adult rats.Neuroscience 55, 81–90.

    Article  PubMed  CAS  Google Scholar 

  • Rebeck G. N., Reiter J. S., Strickland D. K., and Hyman B. T. (1993) Apolipoprotein E in sporadic Alzheimer’s disease: allelic variation and receptor interaction.Neuron 11, 575–580.

    Article  PubMed  CAS  Google Scholar 

  • Roses A. D. (1996) Apolipoprotein E alleles as risk factors in Alzheimer’s disease.Annu. Rev. Med. 47, 387–400.

    Article  PubMed  CAS  Google Scholar 

  • Saunders A. M., Strittmatter W. J., Schmechel D., St. George-Hyslop P. J., Pericak-Vance M. A., Joo S. H., et al. (1993) Association of apolipoprotein E allele 4 with late-onset familial and sporadic Alzheimer’s disease.Neurology 43, 1467–1472.

    PubMed  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 

  • Steinberg D., Parthasarathy S., Carew T. E., Khoo J. C., and Witztum J. L. (1989) Beyond cholesterol: modifications of low density lipoprotein that increases its atherogenecity.N. Engl. J. Med. 320, 915–924.

    PubMed  CAS  Google Scholar 

  • Steinbrecher U. P., Witztum J. L., Parthasarathy S., and Steinberg D. (1987) Decrease in reactive amino group during oxidation on endothelial cell modification of LDL. Correlation with changes in receptor-mediated catabolism.Arteriosclerosis 1, 135–143.

    Google Scholar 

  • Strittmatter W. J., Saunders A. M., Schmechel D., Pericak-Vance M., Enghild J., Salvesen G. S. et al. (1993a) Apolipoprotein E: high avidity binding to beta-amyloid and increased frequency of type 4 allele in late onset familial Alzheimer’s disease.Proc. Natl. Acad. Sci. USA 90, 1977–1981.

    Article  PubMed  CAS  Google Scholar 

  • Strittmatter W. J., Weisgraber K. H., Huang D. Y., Dong L. N., Salvesen G. S., Pericak-Vance M., et al. (1993b) Binding of human apolipoprotein E to synthetic amyloid beta peptides: isoform specific effects and implication for late-onset Alzheimer’s disease.Proc. Natl. Acad. Sci. USA 90, 8098–8102.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Albert Y. Sun.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Draczynska-Lusiak, B., Doung, A. & Sun, A.Y. Oxidized lipoproteins may play a role in neuronal cell death in Alzheimer disease. Molecular and Chemical Neuropathology 33, 139–148 (1998). https://doi.org/10.1007/BF02870187

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02870187

Index Entries

Navigation