Hostname: page-component-78c5997874-ndw9j Total loading time: 0 Render date: 2024-11-05T13:12:12.875Z Has data issue: false hasContentIssue false

A novel oxidative stress marker in patients with Alzheimer’s disease: dynamic thiol–disulphide homeostasis

Published online by Cambridge University Press:  04 April 2016

Sadiye Gumusyayla*
Affiliation:
Department of Neurology, Faculty of Medicine, Yıldırım Beyazıt University, Ankara, Turkey
Gonul Vural
Affiliation:
Department of Neurology, Faculty of Medicine, Yıldırım Beyazıt University, Ankara, Turkey
Hesna Bektas
Affiliation:
Department of Neurology, Ankara Atatürk Education and Research Hospital, Ankara, Turkey
Orhan Deniz
Affiliation:
Department of Neurology, Faculty of Medicine, Yıldırım Beyazıt University, Ankara, Turkey
Salim Neselioglu
Affiliation:
Department of Biochemistry, Ankara Atatürk Education and Research Hospital, Ankara, Turkey
Ozcan Erel
Affiliation:
Department of Biochemistry, Faculty of Medicine, Yıldırım Beyazıt University, Ankara, Turkey
*
Sadiye Gumusyayla, MD, Department of Neurology, Faculty of Medicine, Yıldırım Beyazıt University, Ankara, Turkey. Tel: +90 506 282 0234; Fax: +90 312 291 2706; E-mail: [email protected]

Abstract

Objective

The aim of this study was to evaluate the dynamic thiol–disulphide homeostasis as an oxidative stress parameter, using a newly proposed method, in patients with Alzheimer’s disease.

Methods

In total, 97 participants were included in the study. Among them, 51 had been diagnosed with Alzheimer’s disease, and the remaining 46 were healthy individuals. Total thiol (–SH+–S–S–) levels and native thiol (–SH) levels in serum of each participant were measured. The amount of dynamic disulphide bonds (–S–S–) and (–S–S–) ×100/(–SH), (–S–S–) ×100/(–SH+–S–S–), and –SH×100/(–SH+–S–S–) ratios were calculated from these values. The obtained data were used to compare Alzheimer’s disease patients with healthy individuals.

Results

The average total thiol and native thiol levels of patient with Alzheimer’s disease in the study were found to be significantly lower than those levels of healthy individuals. In addition, in the patient group, the –S–S–×100/–S–S+–SH ratio was found to be significantly higher, whereas the –SH×100/–S–S+–SH ratio was found to be significantly lower compared with healthy individuals. Total thiol and native thiol levels, dynamic disulphide bond amount, and –S–S–×100/–SH, –S–S–×100/–S–S+–SH, and –SH×100/–S–S+–SH ratios were not found to be correlated with mini mental state examination score or duration of disease.

Conclusion

Recent studies have shown that oxidative stress is the one of the molecular changes underlying the pathogenesis of Alzheimer’s disease. In this study, we have investigated the dynamic thiol–disulphide homeostasis in patients with Alzheimer’s disease, using a novel method.

Type
Original Articles
Copyright
© Scandinavian College of Neuropsychopharmacology 2016 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Markesbery, WR. Oxidative stress hypothesis in Alzheimer’s disease. Free Radic Biol Med 2001;23:134147.Google Scholar
2. Liang, LP, Ho, YS, Patel, M. Mitochondrial superoxide production in kainate-induced hippocampal damage. Neuroscience 2000;101:563570.CrossRefGoogle ScholarPubMed
3. Steele, ML, Fuller, S, Maczurek, AE, Kersaitis, C, Ooi, L, Münch, G. Chronic inflammation alters production and release of glutathione and related thiols in human U373 astroglial cells. Cell Mol Neurobiol 2013;33:1930.CrossRefGoogle ScholarPubMed
4. Aksenov, MY, Markesbery, WR. Changes in thiol content and expression of glutathione redox system genes in the hippocampus and cerebellum in Alzheimer’s disease. Neurosci Lett 2001;20:141145.CrossRefGoogle Scholar
5. Aksenov, MY, Tucker, HM, Nair, P et al. The expression of key oxidative stress-handling genes in different brain regions in Alzheimer’s disease. J Mol Neurosci 1999;11:151164.Google Scholar
6. Aksenova, MV, Aksenov, MY, Payne, RM et al. Oxidation of cytosolic proteins and expression of creatine kinase BB in frontal lobe in different neurodegenerative disorders. Dement Geriatr Cogn Disord 1999;10:158165.Google Scholar
7. Hensley, K, Hall, N, Subramaniam, R et al. Brain regional correspondence between Alzheimer’s disease histopathology and biomarkers of protein oxidation. J Neurochem 1995;65:21462156.Google Scholar
8. Hensley, K, Carney, JM, Hall, N, Shaus, W, Butterfield, DA. Electron paramagnetic resonance investigations of free radical induced alterations in neocortical synaptosomal membrane protein infrastructure. Free Radic Biol Med 1994;17:321331.Google Scholar
9. Mecocci, P, Macgarvey, U, Kaufman, AE et al. Oxidative damage to mitochondrial DNA shows marked age-dependent increases in human brain. Ann Neurol. 1993;34:609616.CrossRefGoogle ScholarPubMed
10. Erel, O, Neselioglu, S. A novel and automated assay for thiol/disulphide homeostasis. Clin Biochem 2014;47:326332.Google Scholar
11. Turell, L, Radi, R, Alvarez, B. The thiol pool in human plasma: the central contribution of albumin to redox processes. Free Radic Biol Med 2013;65:244253.Google Scholar
12. Cremers, CM, Jakob, U. Oxidant sensing by reversible disulfide bond formation. J Biol Chem 2013;288:2648926496.CrossRefGoogle ScholarPubMed
13. Sen, CK, Packer, L. Thiol homeostasis and supplements in physical exercise. Am J Clin Nutr 2000;72:653669.CrossRefGoogle ScholarPubMed
14. Jones, DP, Liang, Y. Measuring the poise of thiol/disulfide couples in vivo. Free Radic Biol Med 2009;47:13291338.Google Scholar
15. Markesbery, WR, Carney, JM. Oxidative alterations in Alzheimer’s disease. Brain Pathol 1999;9:133146.Google Scholar
16. Marcus, DL, Thomas, C, Rodriguez, C et al. Increased peroxidation and reduced antioxidant activity in Alzheimer’s disease. Exp Neurol 1998;150:4044.Google Scholar
17. Mecoccі, P, Macgarvey, U, Beal, M et al. Oxidative damage to mitochondrial DNA is increased in Alzheimer’s disease. Ann Neurol 1994;36:747751.Google Scholar
18. Palmer, AM. The activity of the pentose phosphate pathway is increased in response to oxidative stress in Alzheimer’s disease. J Neural Transm 1999;106:317328.CrossRefGoogle ScholarPubMed
19. Perry, TL, Yong, VW, Bergeron, C, Hansen, S, Jones, K. Amino acids, glutathione, and glutathione transferase activity in the brains of patients with Alzheimer’s disease. Ann Neurol 1987;21:331336.Google Scholar
20. Smith, CD, Carney, JM, Starke-Reed, PE et al. Excess brain protein oxidation and enzyme dysfunction in normal aging and Alzheimer disease. Proc Natl Acad Sci 1991;88:1054010543.Google Scholar
21. Lovell, MA, Ehmann, WD, Butler, SM, Markesbery, WR. Elevated thiobarbituric acid-reactive substances and antioxidant enzyme activity in the brain in Alzheimer’s disease. Neurology 1995;45:15941601.Google Scholar
22. Subbarao, KV, Richardson, JS, Ang, LC. Autopsy samples of Alzheimer’s cortex show increased peroxidation in vitro. J Neurochem 1990;55:342345.Google Scholar
23. Balazs, L, Leon, M. Evidence of an oxidative challenge in the Alzheimer’s brain. Neurochem Res 1994;19:11311137.CrossRefGoogle ScholarPubMed
24. Palmer, AM, Burns, MA. Selective increase in lipid peroxidation in the inferior temporal cortex in Alzheimer’s disease. Brain Res 1994;645:338342.Google Scholar
25. Hernanz, A, De La Fuente, M, Navarro, M, Frank, A. Plasma aminothiol compounds, but not serum tumor necrosis factor receptor II and soluble receptor for advanced glycation end products, are related to the cognitive impairment in Alzheimer’s disease and mild cognitive impairment patients. Neuroimmunomodulation 2007;14:163167.CrossRefGoogle ScholarPubMed
26. Mccaddon, A, Hudson, P, Hill, D et al. Alzheimer’s disease and total plasma aminothiols. Biol Psychiatry 2003;53:254260.Google Scholar
27. Praticò, D, Clark, CM, Liun, F et al. Increase of brain oxidative stress in mild cognitive impairment: a possible predictor of Alzheimer disease. J Arch Neurol 2002;59:972976.Google Scholar
28. Keller, JN, Schmitt, FA, Scheff, SW et al. Evidence of increased oxidative damage in subjects with mild cognitive impairment. Neurology 2005;64:11521156.Google Scholar
29. Padurariu, M, Ciobica, A, Hritcu, L et al. Changes of some oxidative stress markers in the serum of patients with mild cognitive impairment and Alzheimer’s disease. Neurosci Lett 2010;469:610.Google Scholar