Advanced oxidation protein products in aged with dementia.
Aging (Health aspects)
Oxidative stress (Health aspects)
Demirbilek, Melike Erol
Komurcu, H. Ferhan
Akin, K. Okhan
|Publication:||Name: American Journal of Immunology Publisher: Science Publications Audience: Professional Format: Magazine/Journal Subject: Biological sciences Copyright: COPYRIGHT 2007 Science Publications ISSN: 1553-619X|
|Issue:||Date: April, 2007 Source Volume: 3 Source Issue: 2|
|Topic:||Event Code: 310 Science & research|
|Geographic:||Geographic Scope: Turkey Geographic Code: 7TURK Turkey|
Abstract: The role of increased oxidative stress in the development
of oxidative protein damage in aging have been reported. There is an
important role of oxidative stress on development of dementia. Advanced
oxidation protein products (AOPPs) are novel markers of oxidative
stress. The aim of this study was to compare AOPP levels in healthy aged
person and aged person with dementia. AOPP levels were in the control
group 83.36 [+ or -] 35.51 [micro]mol/L, and 178.78 [+ or -] 110.50
[micro]mol/L in the group with dementia. This elevation in the group
with dementia was statistically significant (p<0.05). AOPP might be a
useful novel indicator of oxidative stress in dementia.
Key words: Advanced glycation end products, advanced oxidation protein products, alzheimer's disease, aging, dementia
Alzheimer's disease (AD) is a progressive dementia affecting large proportion of the aging population . Reactive oxygen species (ROS) may be only primary culprits in some aspects of AD progression. A candidate class of secondary toxins, the reactive carbonyls, are products of oxidative damage to lipids, sugars, and amino acids that can irreversibly alkylate and crosslink proteins . Since oxidative stress is characterised by an imbalance in radical production and antioxidative defence, both are considered to have a major role in the process of age-related neurodegeneration [3,4].
Oxidative stress results from a distruption of the natural balance between pro- and -anti-oxidant system in favor of the former . The free radical theory of aging states that the reactive oxygen species (ROS) cause oxidative damage over the lifetime of the subject . Central nervous system that is containing postmitotic cells which are liable to accumulate oxidative damage over time, is particularly vulnerable to oxidative stress and uses a large amount of oxygen .
Advanced glycation end products (AGEs), the products of nonenzymatic glycation and oxidation of proteins and lipids, accumulated in diverse biological settings, such as diabetes, inflammation, renal failure, aging, atherosclerosis, and neurodegenerative diseases (AD) [8,9]. In some studies threefold more AGE adducts in plaque fractions were isolated from AD brains than the control brains.
Advanced oxidation protein products (AOPPs) were described by Witko-Sarsat et al. (1996) for the first time. They described the presence in the plasma of haemodialysed patient high levels of oxidized proteins that they designated AOPPs. Two UV-visible peaks of absorbance at 340 nm in plasma from haemodialysed patient which were absent in controls. These two peaks, corresponding to a molecular mass of 60 (low molecular weight-LMW) and 600 kDa (high molecular weight-HMW) . Formation of AOPPs could be induced in control plasma by chlorinated oxidants such as chloramines or hypochlorous acid [10,11]. AOPPs resulted from the interaction between such oxidants and plasma proteins. Neutrophils which contitute the most important source of chlorined oxidants due to their high content in myeloperoxidase, might be involved in plasma AOPPs formation .
Interestingly, the significant correlation between AOPPs and neopterin, a marker of macrophage activation, demonstrated that AOPPs were closely linked to phagocyte activation [13,14]. In vivo plasma levels of AOPPs closely correlate with levels of dityrosine, a hallmark of oxidized proteins and with pentosidine, a marker of protein glycation closely related to oxidative stress [10,12].
AOPPs could be determined routinely using a simple protocol to investigate myeloperoxidase (MPO)--induced oxidative stress, correspond to highly oxidized proteins and specifially to human serum albumin (HSA) . AOPPs were defined a novel marker of oxidative damage  and considered as reliable markers to estimate the degree of oxidant-mediated protein damage .
AOPPs were demonstrated in coronary artery disease , diabetes , preterm neonates , and dentritic cell stimulation . In a study, AOPP levels of skeletal muscle in the old rat group were significantly increased compared with those of the adult rats .
In this study plasma AOPPs were measured in people with dementia and healthy old people.
MATERIALS AND METHODS
The study group consisted of 66 subjects. First group (19 female and 11 male) were healthy old men-women (mean age 67.7 [+ or -] 5.19 years). Second group (27 female and 9 male) had dementia (mean age 77.0 [+ or -] 9.54 years). There was no difference at the distributions of ischemic heart disease, diabetes, renal failure and hypertension between the two groups. Both groups were consisted of non smokers. The patients with the MMSE score of [less than or equal to] 26 were included in this study . Venous blood (5-10 ml) was collected in standart sterile polystrene vacuum tubes, with 5 mM EDTA. After centrifugation (600g for 10 min) the plasma was stored at -80 [degrees]C until use.
Determination of AOPPs was based on spectrophotometric detection according to Witko-Sarsat et. al. (1996). Briefly, 200 [micro]l of plasma (diluted 1:5 with phosphate-buffered saline (PBS)), 200 [micro]l of chloramin T (0-100 [micro]mol/L) for calibration and 200 [micro]l of PBS as blank were applied on a microtiter plate. 10 [micro]l of 1.16 M potassium iodide and 20 [micro]l of acetic acid were added to each well and absorbance at 340 nm was measured immediately. Concentration of AOPPs were expressed in chloramine units ([micro]mol/L). The statistical significance was evaluated using independent sample t test and the results were taken as significant at p<0.05.
RESULTS AND DISCUSSION
AOPP levels in the control subjects were 83.36 [+ or -] 35.51 [micro]mol/L, and in the subjects with dementia were 178.78 [+ or -] 110.50 [micro]mol/L (Figure 1).
[FIGURE 1 OMITTED]
The role of increased oxidative stress in the development of oxidative protein damage in aging is a subject of great interest [7,21,22]. Several lines of evidence implicate oxidative stress in neurodegeneration, particularly in AD which is a progressive dementia [1,23]. Dementia is an imbalance in the radical production and the antioxidative defense leading to oxidative stress. These are considered to have a major role in the process of age-related neurodegeneration [3,4]. AGEs, which are formed by a nonenzymatic glycation and oxidation of proteins and lipids, are potentially toxic to cells and are present in brain plaques in AD . Kalousova et al. (2002), observed AGEs and AOPPs in the diabetic patients and determined that AOPPs were elevated significantly in the patients diabetes mellitus type 1 and 2; and the levels were higher in the patients with diabetes mellitus type 2 in comparison with the healthy subjects .
Eskiocak et al. have found that AOPPs were higher in the brain tissue of hypoxic neonatal rats than in the control group . A large amount of data have implicated oxidative stress in the progression of AD and other neurodegenerative diseases. However as far as the authors knowledge there is no study concerning AOPPs in neurodegenerative diseases.
Cakatay et al. investigated the relation between aging and oxidative protein damage parameters and the AOPP levels in the skeletal muscle of the old rat group were significantly increased compared with those of the adult rats .
In this study AOPPs were measured and presented as a possible novel marker of oxidative stress in dementia. It was found that the AOPPs in the old group with dementia were significantly increased when compared to the results in the healthy old people's group.
We thank to Duriye AYDOGDU, Bahar ULGEN, and Nilgun AKSEL for collecting samples.
[1.] Durany, N., G. Munch, T. Michel and P. Riederer, 1999. Investigation on oxidative stress and therapeutical implications in dementia. Eur. Arch. Psychiatry. Clin. Neurosci., 249: 68-73.
[2.] Picklo, M.J., T.J. Montine, V. Amarnath and M.D. Neely, 2002. Carbonyl toxicology and alzheimer's disease. Toxicol. Appl. Pharmacol., 184: 187-197.
[3.] Gsell, W., I. Strein and P. Riederer, 1996. The neurochemistry of alzheimer type, vascular type and mixed type dementias compared. J. Neural. Transm. Suppl., 47: 73-101.
[4.] Rosler, M., W. Retz, J. Thome and P. Riederer, 1998. Free radicals in alzheimer's dementia: currently available therapeutic strategies. J. Neural. Transm. Suppl., 54: 211-219.
[5.] Halliwell, B., J.M. Gutteridge and C.E. Cross, 1992. Free radicals, antioxidants, and human disease: where are we now? J. Lab. Clin. Med., 119: 598-620.
[6.] Cakatay, U., A. Telci, R. Kayali, F. Tekeli, T. Akcay and A. Sivas, 2003. Relation of aging with oxidative protein damage parameters in the rat skeletal muscle. Clin. Biochem., 36: 51-55.
[7.] Pansarasa, O., L. Castanga, B. Colombi, J. Vecchiet, G. Felzani and F. Marzatico, 2000. Age, and sex differences in human skeletal muscle: role of reactive oxygen species. Free. Radic. Res., 33: 287-293.
[8.] Ramasamy, R., S.J. Vanucci, S.S. Yan, K. Herold, S.F. Yan and A.M. Schmidt, 2005. Advanced glycation end products and RAGE: a common thread in aging, diabetes, neurodegeneration and inflammation. Glycobiol., 15: 16-28.
[9.] Kalousova, M., T. Zima, V. Tesar, S. Dusilova-Sulkova and J. Skrha, 2005. Advanced glycoxidation end product in chronic diseases-clinical chemistry and genetic backround. Mutat. Res., 579: 37-46.
[10.] Witko-Sarsat, V., M. Friedlander, C. Capeillere-Blandin, T. Nguyen-Khoa, A.T. Nguyen, J. Zingraff, P. Jungers and B. Descamps-Latscha, 1996. Advanced oxidation protein products as a novel marker of oxidative stress in uremia. Kidney. Int., 49: 1304-1313.
[11.] Witko-Sarsat, V., T. Nguyen-Khoa, P. Jungers, T. Drueke and B. Descamps-Latscha, 1999. Advanced oxidation protein products as a novel molecular basis of oxidative stress in uremia. Nephrol. Dial. Transplant., 14: 76-78.
[12.] Witko-Sarsat, V., M. Friedlander, T. Nguyen-Khoa, C. Capeillere-Blandin, A.T. Nguyen, S. Canteolup, J.M. Dayer, P. Jungers, T. Drueke and B. Descamps-Latscha, 1998. Advanced oxidation protein products as novel mediators of inflamation and monocyte activation in chronic renal failure. J. Immunol., 161: 2524-2532.
[13.] Descamps-Latscha, B. and V. Witko-Sarsat, 2001. Importance of oxidatively modified proteins in chronic renal failure. Kidney. Int., 78: 108-113.
[14.] Witko-Sarsat, V., V. Gausson, A.T. Nguyen, 2003. AOPP-induced activation of human neutrophil and monocyte oxidative metabolism: a potential target for N-acetylcysteine treatment in dialysis patient. Kidney. Int., 64: 82-91.
[15.] Capeillere-Blandin, C., V. Gausson, B. Descamps-Latscha and V. Witko-Sarsat, 2004. Biochemical and spectrophotometric significance for advanced oxidized protein products. Biochim. Biophys. Acta., 1689: 91-102.
[16.] Alderman, C.J., S. Shah, J.C. Foreman, B.M. Chain and D.R. Katz, 2002. The role of advanced oxidation protein products in regulation of dendritic cell function. Free Radic. Biol. Med., 32: 377-385.
[17.] Kaneda, H., J. Taguchi, K. Ogasawara, T. Aizawa and M. Ohno, 2002. Increased level of advanced oxidation protein products in patient with coronary artery disease. Atherosclerosis, 162: 221-225.
[18.] Martin- Gallan, P., A. Carrascoca, M. Gussinye and C. Domingez, 2003. Biomarkers of diabetes- associated oxidative stress and antioxidant status in young diabetic patients with or without subclinical complications. Free Radic. Biol. Med., 34: 1563-1574.
[19.] Buonocore, G., S. Perrone, M. Longini, P. Vezzosi, B. Marzocchi, P. Paffetti and R. Bracci, 2002. Oxidative stress in preterm neonates at birth and on the seventh day of life. Pediatr. Res., 52: 46-49.
[20.] Ahmed, M.B.,2001. Alzheimer's disease: recent advanced in etiology, diagnosis, and management. Tex. Med., 97: 50-58.
[21.] Berlett, B.S. and E.R. Stadtman, 1997. Protein oxidation in aging, disease, and oxidative stress. J. Biol. Chem., 272: 20313-20316.
[22.] Jolitha, A.B., M.V.V. Subramanyam and S. Asha Devi, 2006. Modification by vitamin E and exercise of oxidative stress in regions of aging rat brain: Studies on superoxide dismutase isoenzymes and protein oxidation status. Exp. Gerontol., 41: 753-763.
[23.] Bowling, A.C. and M.F. Beal, 1995. Bioenergetic and oxidative stress in neurodegenerative diseases. Life Sci., 56: 1151-1171.
[24.] Kalousova, M., J. Skrha and T. Zima, 2002. Advanced glycation end-products and advanced idation protein products in patients with diabetes mellitus. Physiol. Res., 51: 597-604.
[25.] Eskiocak, S., F. Tutunculer, U.N. Basaran, A. Taskiran and E. Cakir, 2007. The effect of melatonin on protein oxidation and nitric oxide in the brain tissue of hypoxic neonatal rats. Brain Dev., 29: 19-24.
Melike Erol Demirbilek, Nedret Kilic, H. Ferhan Komurcu, K. Okhan Akin
Gazi University, Faculty of Medicine, Department of Medical Biochemistry, Besevler, 06500 Ankara,
Corresponding Author: Melike Erol Demirbilek, Gazi University, Faculty of Medicine, Department of Medical Biochemistry, Be_evler, 06500 Ankara, Turkey Tel: +905327111244 Fax: +903122124647
|Gale Copyright:||Copyright 2007 Gale, Cengage Learning. All rights reserved.|