Skip to main content
SpringerLink
Log in

Evaluation of Antioxidants, Protein, and Lipid Oxidation Products in Blood from Sporadic Amiotrophic Lateral Sclerosis Patients

  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Several parameters indicators of oxidative stress were evaluated in blood from individuals with the sporadic form of amiotrophic lateral sclerosis (SALS) and compared to healthy controls. Plasma levels of 2-thiobarbituric-reactive substances (TBARS), products of lipid peroxidation, were significantly higher (p < 0.03) in the SALS patients compared to controls. The concentration of plasma antioxidants (α-tocopherol, β-carotene, ubiquinol-10 and glutathione) and the activity of red blood cell CuZn superoxide dismutase were not significantly different between the groups. The ratio TBARS/α-tocopherol was 47% higher in the SALS individuals than in controls. Protein thiols and protein-associated carbonyls in red blood cell membranes and supernates were similar for both groups. A positive correlation (r2 = 0.91) was found between the concentration of protein-associated carbonyls in red blood cells and the onset of clinical symptoms. These findings are in agreement with several reports showing higher levels of oxidative damage to cell components in ALS.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. Eisen, A. 1995. Amyotrophic lateral sclerosis is a multifactorial disease. Muscle and Nerve 18:741–752.

    Google Scholar 

  2. Rosen, D. R., Siddique, T., Patterson, D., Figlewicz, D. A., Sapp, P., Hentati, A., Donaldson, D., Goto, J., O'Regan, J. P., Deng, H-X., Rahmani, Z., Krizus, A., McKenna-Yasek, D., Cayabyab, A., Gaston, S. M., Berger, R., Tanzi, R. E., Halperin, J. J., Herzfeldt, B., Van den Bergh, R., Hung, W-Y., Bird, T., Deng, G., Mulder, D. W., Smyth, C., Laing, N. G., Soriano, E., Pericak-Vance, M. A., Haines, J., Rouleau, G. A., Gusella, J. S., Horvitz, H. R., and Brown, R. H. Jr. 1993. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362:59–62.

    Google Scholar 

  3. Deng, H. X., Hentati, A., Tainer, J. A., Iqbal, Z., Cayabyab, A., Hung, W-Y., Getzoff, E. D., Hu, P., Herzfeldt, B., Roos, R. P., Warner, C., Deng, G., Soriano, E., Smyth, C., Parge, H. E., Ahmed, A., Roses, A. D., Hallewell, R. A., Pericak-Vance, M. A., and Siddique, T. 1993. Amyotrophic lateral sclerosis and structural defects in Cu, Zn superoxide dismutase. Science 261:1047–1050.

    Google Scholar 

  4. Gurney, M. E., Pu, H., Chiu, A. Y., Dal Canto, M. C., Polchow, C. Y., Alexander, D. D., Caliendo, J., Hentati, A., Kwon, Y. W., Deng, H-X., Chen, W., Zhai, P., Sufit, R. L., and Siddique, T. 1994. Motor neuron degeneration in mice that express a human Cu, Zn superoxide dismutase mutation. Science 264:1772–1775.

    Google Scholar 

  5. Andersen, P. M., Nilsson, P., Ala-Hurula, V., Keranen, M., Tarvainen, I., Haltia, T., Nilsson, L., Binzer, M., Forsgren, L., and Marklund, S. L. 1995. Amyotrophic lateral sclerosis associated with homozygosity for an Asp90Ala mutation in CuZn-superoxide dismutase. Genetics 10:61–66.

    Google Scholar 

  6. Borchelt, D. R., Guarnieri, M., Wong, P. C., Lee, M. K., Slunt, H. S., Xu, Z., Sisodia, S. S., Price, D. L., and Cleveland, D. W. 1995. Superoxide dismutase 1 subunits with mutations linked to familial amyotrophic lateral sclerosis do not affect wild-type subunit function. J. Biol. Chem. 270:3234–3238.

    Google Scholar 

  7. Ames, B. N., Shigenaga, M. K., and Hagen, T. M. 1993. Oxidants, antioxidants, and the degenerative diseases of aging. Proc. Natl. Acad. Sci. USA. 90:7915–7922.

    Google Scholar 

  8. Fraga, C. G., Leibovitz, B. E., and Tappel, A. L. 1988. Lipid peroxidation measured as thiobarbituric acid reactive substances in tissue slices: characterization and comparison with homogenates and microsomes. Free Radical. Biol. Med. 4:155–161.

    Google Scholar 

  9. Motchnik, P. M., Frei, B., and Ames, B. N. 1994. Measurement of antioxidants in human blood plasma. Meth. Enzymol. 234:269–279.

    Google Scholar 

  10. Flohé, L., and Otting F. 1984. Superoxide dismutase assays. Meth. Enzymol. 105:93–104.

    Google Scholar 

  11. Oliver, C. N., Bong-whan A., Moerman, E. J., Goldstein, S, and Stadtman, E. R. 1987. Age-related changes in oxidized proteins. J. Biol. Chem. 262:5488–5491.

    Google Scholar 

  12. Levine, R. L., Garland, D., Oliver, C., Amici, A., Climent, I., Lenz, A., Ahn, B., Shaltiel, S., and Stadtman, E. 1990. Determination of carbonyl content in oxidatively modified proteins. Meth. Enzymol. 186:464–478.

    Google Scholar 

  13. Lou, M. F., Poulsen, L. L., and Ziegler D. M. 1987. Cellular protein-mixed disulfides. Meth. Enzymol. 143:124–129.

    Google Scholar 

  14. Bradford, M. M. 1976. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principles of protein-dye binding. Anal. Biochem. 72:248–254.

    Google Scholar 

  15. Bowling, A. C., Barkowski, E. E., McKenna-Yasek, D., Sapp, P., Horvitz, R. H., Beal F., and Brown, R. H. Jr. 1995. Superoxide dismutase concentration and activity in familial amyotrophic lateral sclerosis. J. Neurochem. 64:2366–2369.

    Google Scholar 

  16. Ogasawara, M., Matsubara, Y., Narisawa, K., Aoki, M., Nakamura, S., Itoyama, Y., and Abe, K. 1993. Mild ALS in Japan associated with novel SOD mutation. Nature Genet. 5:323–324.

    Google Scholar 

  17. Robberecht, W., Sapp, P., Viaene, M. K., Rosen, D., McKenna-Yasek, D., Haines, J., Horvitz, R., Theys, P., and Brown, R. Jr. 1994. Cu/Zn superoxide dismutase activity in familial and sporadic amyotrophic lateral sclerosis. J. Neurochem. 62:384–387.

    Google Scholar 

  18. Abe, K., Pan, L. H., Watanabe, M., Kato, T., and Itoyama, Y. 1995. Induction of nitrotyrosine-like immunoreactivity in the lower motor neuron of amyotrophic lateral sclerosis. Neurosci. Letters. 199:152–154.

    Google Scholar 

  19. Bowling, A. C., Schulz, J. B., Brown, R. H. Jr., and Beal, F. 1993. Superoxide dismutase activity, oxidative damage, and mitochondrial energy metabolism in familial and sporadic amyotrophic lateral sclerosis. J. Neurochem. 61:2322–2325.

    Google Scholar 

  20. Rosen, D. R., Bowling, A. C., Patterson, D., Usdin, T. B., Sapp, P., Mezey, E., McKenna-Yasek, D., O'Regan, J. P., Rhamani, Z., Ferrante, R. J., Brownstein, M. J., Kowall, N. W., Beal, M. F., Horvitz, H. R., and Brown, R. H. Jr. 1994. A frequent Ala 4 to Val mutation in exon 1 of the superoxide dismutase-1 gene: decreased enzyme activity is associated with a rapidly progressive familial ALS. Hum. Mol. Genet. 3:981–987.

    Google Scholar 

  21. Riemersma, R. A., Wood, D. A., Macintyre, C. C. A., Elton, R. A., Gey, K. F., and Oliver, M. F. 1991, Risk of angina pectoris and plasma concentrations of vitamins A,C, and E and carotene. Lancet 337:1–5.

    Google Scholar 

  22. Ihara, Y., Mori, A., Hayabara, T., Kawai, M., Namba, R., Nobukuni, K., Sato, K., and Kibata, M. 1995. Superoxide dismutase and free radicals in sporadic amyotrophic lateral sclerosis: relationship to clinical data. J. Neurol. Sci. 134:51–56.

    Google Scholar 

  23. Yim, M. B., Kang, J. H., Yim, H. S., Kwak, H. S. Chock, P. B., and Stadtman, E. R. 1996. A gain of function of an amyotrophic lateral sclerosis-associated Cu, Zn-superoxide dismutase mutant: An enhancement of free radical formation due to a decrease in Km for hydrogen peroxide. Proc. Natl. Acad. Sci. USA. 93:5709–5714.

    Google Scholar 

  24. Wiedau-Pazos, M., Goto, J. J., Rabizadeh, S., Gralla, E. B., Roe, J. A., Lee, M. K., Valentine, J. S., and Bredesen, D. E. 1996. Altered reactivity of superoxide dismutase in familial amyotrophic lateral sclerosis. Science. 271:515–518.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departmento de Química Biológica (IQUIFIB-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina

    Patricia I. Oteiza

  2. Instituto de Biología Celular y Neurociencia Prof. E. D. De Robertis, Facultad de Medicina, Universidad de Buenos Aires, Argentina

    Osvaldo D. Uchitel

  3. Fisicoquímica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina

    Fernando Carrasquedo & Cesar G. Fraga

  4. Centre Neurológico, Hospital Francés, Buenos Aires

    Alberto L. Dubrovski & Juan C. Roma

Authors
  1. Patricia I. Oteiza
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Osvaldo D. Uchitel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fernando Carrasquedo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alberto L. Dubrovski
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Juan C. Roma
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Cesar G. Fraga
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Oteiza, P.I., Uchitel, O.D., Carrasquedo, F. et al. Evaluation of Antioxidants, Protein, and Lipid Oxidation Products in Blood from Sporadic Amiotrophic Lateral Sclerosis Patients. Neurochem Res 22, 535–539 (1997). https://doi.org/10.1023/A:1027384432715

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1027384432715

Search

Navigation