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Are children with down syndrom under the oxidative stress?
I371
I372
I
THE FORMATION OF REACTIVE SPECBB BY RED CELIS OF SICKJXCELLPATIENTS
MYELOPEROXIDASE-DEFICIENCY INCREASED ATHEROSCLEROSIS
RESULTS IN IN FAT FED MICE
M L Brentt~~~, D.M.Shih, M.M.Anderson*, W.Shi, X.P.Wang, f.W.Heinecke’ and A.j.iusis De t. Medicine, UCLA, Los Angeles, CA E* ‘Dept. Medicine, WUSTL, St. Louis, M B
Myeloperoxidase (MPO), a heme containing enzyme in monocytes and neutrophils, has been hypothesized to inflict oxidative damage at sites of inflammation. One such example is atherosclerotic plaque where MI’0 and its reaction products are detected. To test this hypothesis, a low density lipoprotein receptor (LDLR)-deficient mouse model that develops fibrous lesions when placed on a high fat diet was utilized. Since MPO is expressed only in blood cells, we used bone marrow transplantation to create combined MPO-deficient, LDLR-deficient mice. The mice were maintained for 14 weeks on a high fat, high cholesterol diet. White cell counts and plasma lipoprotein profiles were similar between the two groups at sacrifice. Cross-sectional analysis of the aortic root indicated that lesions in MI’O-deficient mice were about 50% larger than controls. MPO wild-type/LDLR-deficient mice exhibited an average lesion area of 24.5 zt 1.6 X 10” pm
METABOLISM OF GLUTATHIONE AT THE PERSONS WITH DOWN SYNDROM ilrwnCko,~b Z. ‘, Gnrcuo,~~ I.‘, M~rchovti J ‘, L/p/tiko,ri A.’
cmd
‘Department of Medical Chemistry and Biochemistry, Faculty of Comenius University, Bratislava, ‘Institut of Medicine, Preventive and Clinical Medicine, Bratislava, Slovak Republic e-mail durackova@,fmed uniba sk Down syndrom (DS) is the phenotyp expression of human trisomie 21 It is assumed that the persons with DS are under the elevated oxidative stress thanks to increased activity of Cu/Znsuperoxide dismutase (SOD), which is coded on the chromosome 21. We were interested in the levels of oxidized (GSSG) and reduced (GSH) glutathione and their ration (GSWGSSG) in the correlation to malondialdehyde (MDA), lipofuscine as well as to the glutathione perovidase (Gl’x), glutathione reductase (GR) activities and representative low molecular weight antioxidants (vitamin E and uric acid) of 37 persons with DS The control group was composed from brothers and sisters of DS subjects At the persons with DS decreasing level of GSH was found and the ratio GSH/GSSG was reduced in age dependence Negative correlation between the ratio GSWGSSG and MDA or lipofuscine refer to the protective effect of GSH before the oxidative stress at DS subjects The negative correlation between GSWGSSG ratio and uric acid level as well as the positive correlation between GSWGSSG ratio and vitamin E testify to different co-operation between antioxidants
s120
OXYGEN
ARE CHILDREN WITH DOWN SYNDROM UNDER THE OXIDATIVE STRESS? IjwnCkowi Z. ‘, $trstrovri M’, Mrchowi .J.‘, Gcrrzrio~filI’ nd Lyaikowi A.’ ‘Department of Medical Chemistry and Biochemistry. Faculty of Medicine, Comenius University, Bratislava, ‘Institute of Preventive and Clinical Medicine, Bratislava, Slovak Republic e-mail: durackova@fmed uniba.sk Down syndrom (DS), the phenotyp expression of human trisomy 21, is the most frequent chromosomal aberration in live births Duplication of chromosome 21 causes the DS phenotype including immunodeficiency, morphological abnormalities, neurodegeneration, mental retardation, increased risk of leukemia and premature aging. C&n-superoxide dismutase (SOD) is coded on the chromosom 21 Increased gene dose for SOD causes increased SOD activity, which could be the reason for raised oxidative stress at DS persons We have determined the activities of SOD. glutathione peroxidase (GPx), catalase (CA), myeloperoxidase (MPx) and glutathione reductase (GR) in erythrocytes and PMIU leukocytes of 37 persons with DS and compared them with the values of their health brothers and sisters We calculated the correlation of these activities with malondialdehyde (MDA), lipofuscine and age The statistical important increasing of the activity of SOD, GPx and MDA was found The increased ratio of SODI(GPx + CA) at the DS subjects in comparison with the control group and the positive correlation between this ratio and MDA at DS was found This oxidative disequillibrium could contribute to the premature ageing of persons with DS
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9
I372
I
THE FORMATION OF REACTIVE SPECBB BY RED CELIS OF SICKJXCELLPATIENTS
MYELOPEROXIDASE-DEFICIENCY INCREASED ATHEROSCLEROSIS
RESULTS IN IN FAT FED MICE
M L Brentt~~~, D.M.Shih, M.M.Anderson*, W.Shi, X.P.Wang, f.W.Heinecke’ and A.j.iusis De t. Medicine, UCLA, Los Angeles, CA E* ‘Dept. Medicine, WUSTL, St. Louis, M B
Myeloperoxidase (MPO), a heme containing enzyme in monocytes and neutrophils, has been hypothesized to inflict oxidative damage at sites of inflammation. One such example is atherosclerotic plaque where MI’0 and its reaction products are detected. To test this hypothesis, a low density lipoprotein receptor (LDLR)-deficient mouse model that develops fibrous lesions when placed on a high fat diet was utilized. Since MPO is expressed only in blood cells, we used bone marrow transplantation to create combined MPO-deficient, LDLR-deficient mice. The mice were maintained for 14 weeks on a high fat, high cholesterol diet. White cell counts and plasma lipoprotein profiles were similar between the two groups at sacrifice. Cross-sectional analysis of the aortic root indicated that lesions in MI’O-deficient mice were about 50% larger than controls. MPO wild-type/LDLR-deficient mice exhibited an average lesion area of 24.5 zt 1.6 X 10” pm
METABOLISM OF GLUTATHIONE AT THE PERSONS WITH DOWN SYNDROM ilrwnCko,~b Z. ‘, Gnrcuo,~~ I.‘, M~rchovti J ‘, L/p/tiko,ri A.’
cmd
‘Department of Medical Chemistry and Biochemistry, Faculty of Comenius University, Bratislava, ‘Institut of Medicine, Preventive and Clinical Medicine, Bratislava, Slovak Republic e-mail durackova@,fmed uniba sk Down syndrom (DS) is the phenotyp expression of human trisomie 21 It is assumed that the persons with DS are under the elevated oxidative stress thanks to increased activity of Cu/Znsuperoxide dismutase (SOD), which is coded on the chromosome 21. We were interested in the levels of oxidized (GSSG) and reduced (GSH) glutathione and their ration (GSWGSSG) in the correlation to malondialdehyde (MDA), lipofuscine as well as to the glutathione perovidase (Gl’x), glutathione reductase (GR) activities and representative low molecular weight antioxidants (vitamin E and uric acid) of 37 persons with DS The control group was composed from brothers and sisters of DS subjects At the persons with DS decreasing level of GSH was found and the ratio GSH/GSSG was reduced in age dependence Negative correlation between the ratio GSWGSSG and MDA or lipofuscine refer to the protective effect of GSH before the oxidative stress at DS subjects The negative correlation between GSWGSSG ratio and uric acid level as well as the positive correlation between GSWGSSG ratio and vitamin E testify to different co-operation between antioxidants
s120
OXYGEN
ARE CHILDREN WITH DOWN SYNDROM UNDER THE OXIDATIVE STRESS? IjwnCkowi Z. ‘, $trstrovri M’, Mrchowi .J.‘, Gcrrzrio~filI’ nd Lyaikowi A.’ ‘Department of Medical Chemistry and Biochemistry. Faculty of Medicine, Comenius University, Bratislava, ‘Institute of Preventive and Clinical Medicine, Bratislava, Slovak Republic e-mail: durackova@fmed uniba.sk Down syndrom (DS), the phenotyp expression of human trisomy 21, is the most frequent chromosomal aberration in live births Duplication of chromosome 21 causes the DS phenotype including immunodeficiency, morphological abnormalities, neurodegeneration, mental retardation, increased risk of leukemia and premature aging. C&n-superoxide dismutase (SOD) is coded on the chromosom 21 Increased gene dose for SOD causes increased SOD activity, which could be the reason for raised oxidative stress at DS persons We have determined the activities of SOD. glutathione peroxidase (GPx), catalase (CA), myeloperoxidase (MPx) and glutathione reductase (GR) in erythrocytes and PMIU leukocytes of 37 persons with DS and compared them with the values of their health brothers and sisters We calculated the correlation of these activities with malondialdehyde (MDA), lipofuscine and age The statistical important increasing of the activity of SOD, GPx and MDA was found The increased ratio of SODI(GPx + CA) at the DS subjects in comparison with the control group and the positive correlation between this ratio and MDA at DS was found This oxidative disequillibrium could contribute to the premature ageing of persons with DS
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