Age-dependent changes of glyoxalase I expression in human brain.
ABSTRACT Increased modification and crosslinking of proteins by advanced glycation end products (AGEs) is a characteristic feature of aging, and contributes to the formation of many of the lesions of neurodegenerative diseases including neurofibrillary tangles and amyloid plaques in Alzheimer's disease. Therefore, defense mechanisms against AGE formation or detoxification of their precursors such as the glyoxalase system are of particular interest in aging research. Thus, we investigated the age-dependent protein expression, the activity as well as the RNA level of glyoxalase I in Brodmann area 22 (auditory association area of superior temporal gyrus) of the human cerebral cortex. Our immunohistochemical results demonstrate the localization of glyoxalase I in neurons, predominantly pyramidal cells, as well as in astroglia, located predominantly in the subpial region. The number of glyoxalase I expressing neurons and astroglia increases with age, with a peak at approximately 55 years, and progressively decreases thereafter. These results were confirmed by biochemical investigations in total brain tissue, where the RNA, the protein level as well as the activity of glyoxalase I enzyme were analyzed in different age groups. In conclusion, the increase in glyoxalase I expression up to the age of 55 may be a compensatory mechanism against high oxoaldyde levels and the accumulation of AGEs. However, the decline of glyoxalase expression and activity in old age, possibly caused by impairment in transcription or/and translation, may subsequently lead to increased levels of reactive carbonyl compounds, followed by protein crosslinking, inflammation, oxidative stress and neuronal degeneration.
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ABSTRACT: Based on Das and Dey (2007), this paper designs and implements a periodic controller to achieve, via zero-placement, robustness of a physical Cart–Inverted Pendulum system with respect to differential gain variations in the output sensors. Experimental results that verify the superiority of this controller over linear time-invariant (LTI) ones are also presented.Automatica 01/2011; 47:2543-2547. · 2.92 Impact Factor
- Aging 01/2011; 3(1):5-9. · 4.70 Impact Factor
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ABSTRACT: Objectives: Diabetes mellitus is one of the most frequent stroke-related comorbid states, and it is characterized by accumulation of reactive carbonyl compounds (RCOs), leading to "carbonyl stress". This pilot study was aimed to evaluate the effect of the consumption of the nutritional supplement ALAnerv(®) on some serum carbonyl stress markers, as well as on the activity of erythrocytes' glyoxalases in post-acute stroke patients undergoing rehabilitation.Material and Methods: We created a study population of 28 patients, organized into (-) ALA and (+) ALA groups. Patients from (+) ALA group received ALAnerv(®) for two weeks (2 pills/day). All the subjects followed the same rehabilitation program. In both groups, blood samples were taken at the hospitalization and at the discharge moments, respectively. On these samples we assessed lactic acid, fructosamine and RCOs concentrations, as well as the activities of glyoxalases 1 and 2 from erythrocytes' lysates.Outcomes: In (-) ALA group the concentrations of fructosamine and RCOs significantly increased (0.90 ± 0.04 vs. 1.02 ± 0.04, p = 0.020; 0.19 ± 0.03 vs. 0.28 ± 0.07, p = 0.027) during the study period. Also, glyoxalase 2 activity decreased in this group (27.04 ± 6.10 vs. 14.43 ± 3.02, p = 0.027). In (+) ALA group, the variation of these parameters did not reach statistical significance. Only, the activity of Glo1, which catalyzes the rate-limiting step in the glyoxalase pathway, had an increasing trend in (+) ALA group. The percentage of variation of fructosamine between (-) ALA and (+) ALA groups reached statistical significance (14.8 ± 5.2 vs. - 1.0 ± 13.3, p = 0.047). Regression analysis indicated that the activity of glyoxalase 2 was significantly influenced by the treatment with ALAnerv(®) (p < 0.001), while the concentration of RCOs was significantly influenced by diabetes mellitus (p = 0.030).Conclusions: Our preliminary results suggest that ALAnerv(®) could be useful for the correction of the carbonyl stress status in post-acute stroke patients with diabetes. Also, this study underlines the need of a longer treatment period with a higher dose.Mædica. 09/2013; 8(3):249-55.