共查询到20条相似文献,搜索用时 15 毫秒
1.
Hypobaric hypoxia induces oxidative stress in rat brain 总被引:7,自引:0,他引:7
Maiti P Singh SB Sharma AK Muthuraju S Banerjee PK Ilavazhagan G 《Neurochemistry international》2006,49(8):709-716
High altitude exposure results in decreased partial pressure of oxygen and an increased formation of reactive oxygen and nitrogen species (RONS), which causes oxidative damage to lipids, proteins and DNA. Exposure to high altitude appears to decrease the activity and effectiveness of antioxidant enzyme system. The antioxidant system is very less in brain tissue and is very much susceptible to hypoxic stress. The aim of the present study was to investigate the time dependent and region specific changes in cortex, hippocampus and striatum on oxidative stress markers on chronic exposure to hypobaric hypoxia. The rats were exposed to simulated high altitude equivalent to 6100 m in animal decompression chamber for 3 and 7 days. Results indicate an increase in oxidative stress as seen by increase in free radical production, nitric oxide level, lipid peroxidation and lactate dehydrogenase levels. The magnitude of increase in oxidative stress was more in 7 days exposure group as compared to 3 days exposure group. The antioxidant defence system such as reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD) and reduced/oxidized glutathione (GSH/GSSG) levels were significantly decreased in all the three regions. The observation suggests that the hippocampus is more susceptible to hypoxia than the cortex and striatum. It may be concluded that hypoxia differentially affects the antioxidant status in the cortex, hippocampus and striatum. 相似文献
2.
The steady-state levels of oxidative DNA damage and of lipid peroxidation (F2-isoprostanes) are not correlated in healthy human subjects 总被引:2,自引:0,他引:2
England T Beatty E Rehman A Nourooz-Zadeh J Pereira P O'Reilly J Wiseman H Geissler C Halliwell B 《Free radical research》2000,32(4):355-362
Oxidative damage to DNA in human tissues can be determined by measuring multiple products of oxidative damage to the purine and pyrimidine bases using gas chromatography-mass spectrometry (GC-MS). Oxidative damage to lipids (lipid peroxidation) can be quantitated by the mass spectrometry-based determination of F2-isoprostanes, specific end-products of the peroxidation of arachidonic acid residues in lipids. For both DNA base damage products and 8-epi prostaglandin F2alpha (PGF2alpha), there is a wide variation in levels between different healthy human subjects. We measured multiple products of oxidative damage to DNA bases in white cells, and 8-epi PGF2alpha in plasma, from blood samples obtained from healthy human subjects in the UK and in Portugal. No correlation of 8-epi PGF2alpha levels with levels of any modified DNA base (including 8-hydroxyguanine) was observed. We conclude that no single parameter can be measured as an index of "oxidative stress" or "oxidative damage" in vivo. 相似文献
3.
Viganò A Ripamonti M De Palma S Capitanio D Vasso M Wait R Lundby C Cerretelli P Gelfi C 《Proteomics》2008,8(22):4668-4679
High altitude hypoxia is a paraphysiological condition triggering redox status disturbances of cell organization leading, via oxidative stress, to proteins, lipids, and DNA damage. In man, skeletal muscle, after prolonged exposure to hypoxia, undergoes mass reduction and alterations at the cellular level featuring a reduction of mitochondrial volume density, accumulation of lipofuscin, a product of lipid peroxidation, and dysregulation of enzymes whose time course is unknown. The effects of 7-9 days exposure to 4559 m (Margherita Hut, Monte Rosa, Italy) on the muscle proteins pattern were investigated, pre- and post-exposure, in ten young subjects, by 2-D DIGE and MS. Ten milligram biopsies were obtained from the mid part of the vastus lateralis muscle at sea level (control) and at altitude, after 7-9 days hypoxia. Differential analysis indicates that proteins involved in iron transport, tricarboxylic acid (TCA) cycle, oxidative phosphorylation, and oxidative stress responses were significantly (p<0.05) decreased in hypoxia. Parenthetically, hypoxia markers such as hypoxia inducible factor 1 alpha (HIF-1alpha) and pyruvate dehydrogenase kinase 1 (PDK1) were still at the pre-hypoxia levels, whereas the mammalian target of rapamycin (mTOR), a marker of protein synthesis, was reduced. 相似文献
4.
Timothy England Emily Beatty Almas Rehman Jaffar Nourooz-Zadeh Paulo Pereira James O'Reilly 《Free radical research》2013,47(4):355-362
Oxidative damage to DNA in human tissues can be determined by measuring multiple products of oxidative damage to the purine and pyrimidine bases using gas chromatography-mass spectrometry (GC-MS). Oxidative damage to lipids (lipid peroxidation) can be quantitated by the mass spectrometry-based determination of F2-isoprostanes, specific end-products of the peroxidation of arachidonic acid residues in lipids. For both DNA base damage products and 8-epi prostaglandin F2α (PGF2α), there is a wide variation in levels between different healthy human subjects. We measured multiple products of oxidative damage to DNA bases in white cells, and 8-epi PGF2α in plasma, from blood samples obtained from healthy human subjects in the UK and in Portugal. No correlation of 8-epi PGF2α levels with levels of any modified DNA base (including 8-hydroxyguanine) was observed. We conclude that no single parameter can be measured as an index of “oxidative stress” or “oxidative damage” in vivo. 相似文献
5.
Aluminium-induced production of oxygen radicals, lipid peroxidation and DNA damage in seedlings of rice (Oryza sativa) 总被引:4,自引:0,他引:4
The effect of aluminium (Al) on seedlings of two rice cultivars, Pusa Basmati and Vikas was investigated after different hours of exposure to 80 mol/L of external Al supply. With increasing time of exposure, the growing seedlings readily absorbed Al and its localization was greater in roots than shoots. Prolonged exposure to Al intensified lipid peroxidation, changed the activities of SOD and peroxidase and caused DNA damage. However, differential responses were observed between the seedlings of two rice cultivars under Al stress. A close inverse relationship existed between decreased root growth and increased Al accumulation, lipid peroxidation, SOD, peroxidase activities and DNA damage. The results demonstrate that roots are the major sites of Al localization and accumulation of Al promoted oxygen free radicals mediated peroxidation of membranes as evidenced by increased MDA levels and the activities of SOD and peroxidase. Our results for the first time showed that Al can cause DNA damage in rice. 相似文献
6.
Relative efficacies of indole antioxidants in reducing autoxidation and iron-induced lipid peroxidation in hamster testes 总被引:2,自引:0,他引:2
Increased iron stores are associated with free radical generation and carcinogenesis. Lipid peroxidation is involved in DNA damage, thus indirectly participating in the early steps of tumor initiation. Melatonin and structurally related indoles are effective in protecting against oxidative stress. The aim of the study was to compare the relative efficacies of melatonin, N-acetylserotonin (NAS), indole-3-propionic acid (IPA), and 5-hydroxy-indole-3-acetic acid (5HIAA) in altering basal and iron-induced lipid peroxidation in homogenates of hamster testes. To determine the effect of the indoles on the autoxidation of lipids, homogenates were incubated in the presence of each agent in concentrations of 0.0, 0.01, 0.05, 0.1, 0.25, 0.5, 0.75, 1.0, 2.0, 2.5, or 5.0 mM. To study their effects on induced lipid peroxidation, homogenates were incubated with FeSO(4) (30 microM + H(2)O(2) (0.1 mM) + each of the indoles in the same concentrations as above. The degree of lipid peroxidation was expressed as concentrations of malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA) per mg protein. The indoles decreased both basal and iron-related lipid peroxidation in a concentration-dependent manner. Melatonin reduced basal MDA + 4-HDA levels when used at the concentrations of 0.25 mM or higher, and prevented iron-induced lipid peroxidation at concentrations of 1.0, 2.0, 2.5, or 5.0 mM. The lowest effective concentrations of NAS required to lower basal and iron-related lipid peroxidation were 0.05 mM and 0.25 mM, respectively. IPA, only when used in the highest concentrations of 2.5 mM or 5 mM inhibited basal lipid peroxidation levels and it was ineffective on the levels of MDA + 4-HDA due to iron damage. 5HIAA reduced basal lipid peroxidation when used at concentrations of 0.25 mM or higher, and it prevented iron-induced lipid peroxidation only at the highest applied concentration (5 mM). In conclusion, melatonin and related indoles at pharmacological concentrations protect against both the autoxidation of lipids as well as induced peroxidation of lipids in testes. In doing so, these agents would be expected to reduce testicular cancer that is initiated by products of lipid peroxidation. 相似文献
7.
Opposite effects on antioxidant enzymes of adaptation to continuous and intermittent hypoxia] 总被引:1,自引:0,他引:1
F Z Meerson I I Arkhipenko IVbRozhitskaia V V Didenko T G Sazontova 《Biulleten' eksperimental'no? biologii i meditsiny》1992,114(7):14-15
Adaptation to continuous hypoxia under mid-mountain conditions (altitude 2100 m) decreases the content of lipid peroxidation products and the activity of superoxide dismutase and catalase in rat heart, liver, and brain, with a concomitant decline in the resistance to reperfusion arrhythmias. On the contrary, adaptation to intermittent hypoxia in the altitude chamber increases the activity of the antioxidant enzymes in the same organs, while the content of peroxidation products remains normal; at the same time, the heart becomes more resistant to reperfusion arrhythmias. The mechanism is discussed that ensures enhanced antioxidant protection in adaptation to intermittent hypoxia. 相似文献
8.
Membrane lipid peroxidation processes yield products that may react with DNA and proteins to cause oxidative modifications. In the present study, we evaluated lipid peroxidation-mediated cytotoxicity and oxidative DNA damage in U937 cells. Upon exposure of U937 cells to tert-butylhydroperoxide (t-BOOH) and 2,2'-azobis (2-amidinopropane) hydrochloride (AAPH), which induce lipid peroxidation in membranes, the cells exhibited a reduction in viability and an increase in the endogenous production of reactive oxygen species (ROS), as measured by the oxidation of 2',7'-dichlorodihydrofluorescein. In addition, a significant decrease in the intracellular GSH level and the activities of major antioxidant enzymes were observed. We also observed lipid peroxidation-mediated oxidative DNA damage, reflected by an increase in 8-OH-dG level and loss of the ability of DNA to renature. When the cells were pretreated with the antioxidant N-acetylcysteine (NAC) or the spin trap alpha-phenyl-N-t-butylnitrone (PBN), lipid peroxidation-mediated cytotoxicity in U937 cells was protected. This effect seems to be due to the ability of NAC and PBN to reduce ROS generation induced by lipid peroxidation. These results suggest that lipid peroxidation resulted in a pro-oxidant condition of U937 cells by the depletion of GSH and inactivation of antioxidant enzymes, which consequently leads to a decrease in survival and oxidative damage to DNA. The results indicate that the peroxidation of lipid is probably one of the important intermediary events in oxidative stress-induced cellular damage. 相似文献
9.
Probucol, a clinically used cholesterol lowering and antioxidant drug, was investigated for possible protection against lipid peroxidation and DNA damage induced by iron nitrilotriacetate (Fe-NTA) plus hydrogen peroxide (H2O2). Fe-NTA is a potent nephrotoxic agent and induces acute and subacute renal proximal tubular necrosis by catalyzing the decomposition of H2O2-derived production of hydroxyl radicals, which are known to cause lipid peroxidation and DNA damage. Fe-NTA is associated with a high incidence of renal adenocarcinoma in rodents. Lipid peroxidation and DNA damage are the principal manifestation of Fe-NTA induced toxicity, which could be mitigated by probucol. Incubation of renal microsomal membrane and/or calf thymus DNA with H2O2 (40 mM) in the presence of Fe-NTA (0.1 mM) induces renal microsomal lipid peroxidation and DNA damage to about 2.4-fold and 5.9-fold, respectively, as compared to control (P < 0.05). Induction of renal microsomal lipid peroxidation and DNA damage was inhibited by probucol in a concentration-dependent manner. In lipid peroxidation protection studies, probucol treatment showed a concentration-dependent inhibition (10-34% inhibition; P < 0.05) of Fe-NTA plus H2O2-induced lipid peroxidation as measured by thiobarbituric acid reacting species' (TBARS) formation in renal microsomes. Similarly, in DNA damage protection studies, probucol treatment also showed a concentration-dependent strong inhibition (36-71% inhibition; P < 0.05) of DNA damage. From these studies, it was concluded that probucol inhibits peroxidation of microsomal membrane lipids and DNA damage induced by Fe-NTA plus H2O2. However, because the lipid peroxidation and DNA damage studied here are regarded as early markers of carcinogenesis, we suggest that probucol may be developed as a cancer chemopreventive agent against renal carcinogenesis and other adverse effects of Fe-NTA exposure in experimental animals, in addition to being a cholesterol-lowering drug, useful for the control of hypercholestrolemia. 相似文献
10.
Eduardo A. Almeida Afonso Celso Dias Bainy Osmar F. Gomes Paolo Di Mascio 《Journal of experimental marine biology and ecology》2005,318(1):21-30
Mussels Perna perna were exposed to air for 24 h showing a clear increase in the levels of lipid peroxidation and oxidative DNA damage, measured as 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo). The levels of lipid peroxidation increased both in the digestive gland and gills, while oxidative DNA damage increased only in the gills. After the 24 h of air exposure, mussels were re-submersed for a period of 3 h, leading values to return to a pre-aerial exposure levels. Control animals were kept immersed during the whole period. Several antioxidant and complementary enzymes (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glucose-6-phosphate dehydrogenase (G6PDH), glutathione S-transferase (GST) and the levels of total glutathione (Total GSH) were assayed in a second set of experiments where one group of mussels were exposed to air for 18 h and other to 1 h re-submersion after 18 h aerial exposure. Only a 52% increase in the glutathione S-transferase activity was observed in the digestive gland, which remained elevated to about 40% after 1 h re-submersion, showing that defense systems can be modulated even during oxygen deprivation in P. perna. The DNA and lipid oxidative damage observed after aerial exposure indicates that mussels face an oxidative challenge, and are able to counteract such an “insult” as values of lipid peroxidation and DNA damage returned to control values after 3 h re-submersion. 相似文献
11.
H Rauchová M Vokurková J Koudelová 《Physiological research / Academia Scientiarum Bohemoslovaca》2012,61(Z1):S89-S101
Reactive oxygen species (ROS) are common products of the physiological metabolic reactions, which are associated with cell signaling and with the pathogenesis of various nervous disorders. The brain tissue has the high rate of oxidative metabolic activity, high concentration of polyunsaturated fatty acids in membrane lipids, presence of iron ions and low capacity of antioxidant enzymes, which makes the brain very susceptible to ROS action and lipid peroxidation formation. Membranes of brain cortex show a higher production of thiobarbituric acid-reactive substances (TBARS) in prooxidant system (ADP.Fe(3+)/NADPH) than membranes from the heart or kidney. Lipid peroxidation influences numerous cellular functions through membrane-bound receptors or enzymes. The rate of brain cortex Na(+),K(+)-ATPase inhibition correlates well with the increase of TBARS or conjugated dienes and with changes of membrane fluidity. The experimental model of short-term hypoxia (simulating an altitude of 9000 m for 30 min) shows remarkable increase in TBARS in four different parts of the rat brain (cortex, subcortical structures, cerebellum and medulla oblongata) during the postnatal development of Wistar rat of both sexes. Young rats and males are more sensitive to oxygen changes than adult rats and females, respectively. Under normoxia or hypobaric hypoxia both ontogenetic aspects and sex differences play a major role in establishing the activity of erythrocyte catalase, which is an important part of the antioxidant defense of the organism. Rats pretreated with L-carnitine (and its derivatives) have lower TBARS levels after the exposure to hypobaric hypoxia. The protective effect of L-carnitine is comparable with the effect of tocopherol, well-known reactive species scavenger. Moreover, the plasma lactate increases after a short-term hypobaric hypoxia and decreases in L-carnitine pretreated rats. Acute hypobaric hypoxia and/or L-carnitine-pretreatment modify serum but not brain lactate dehydrogenase activity. The obtained data seem to be important because the variations in oxygen tension represent specific signals of regulating the activity of many specific systems in the organism. 相似文献
12.
Gulumian M 《Redox report : communications in free radical research》2000,5(6):325-351
Exposure to pathogenic mineral dusts and fibres is associated with pulmonary changes including fibrosis and cancer. Investigations into aetiological mechanisms of these diseases have identified modifications in specific macromolecules as well as changes in certain early processes, which have preceded fibrosis and cancer. Peroxidation of lipids is one such modification, which is observed following exposure to mineral dusts and fibres. Their ability to initiate lipid peroxidation and the parameters that determine this ability have recently been reviewed. Part II of this review examines the relationship between the capacity of mineral dusts and fibres to initiate lipid peroxidation and a number of pathological changes they produce. The oxidative modification of polyunsaturated fatty acids is a major contributor to membrane damage in cells and has been implicated in a great variety of pathological processes. In most pathological conditions where an induction of lipid peroxidation is observed it is assumed to be the consequence of disease, without further establishing if the induction of lipid peroxidation may have preceded or accompanied the disease. In the great majority of instances, however, despite the difficulty in proving this association, a causal relationship between lipid peroxidation and disease cannot be ruled out. 相似文献
13.
The interaction of lipid peroxidation products with nuclear macromolecules was investigated in rat liver nuclei labelled with [3H]arachidonic acid. Lipid peroxidation reactions were driven both non-enzymatically and enzymatically by the addition of ascorbate-Fe2+ or NADPH-ADP-Fe3+, respectively, to the incubation mixtures. The extent of peroxidation was evaluated by the formation of thiobarbituric acid chromophore and of radioactive hydrophilic peroxidation products. The results obtained show that: (1) nuclear membrane lipid peroxidation products formed during incubation interact with DNA and total nuclear proteins; (2) non-enzymatic lipid peroxidation processes induced a 40% larger association of peroxidation products to DNA compared to processes driven enzymatically, whereas the corresponding interaction with total nuclear proteins was similar in both peroxidation systems; (3) the radioactivity associated with histones decreased during incubation in the presence of ascorbate-Fe2+ or NADPH-ADP-Fe3+, and increased in control samples (no additions); (4) inhibition of lipid peroxidation by the iron chelator Desferrioxamine B prevented the association of peroxidation products to nuclear macromolecules; (5) the levels of radioactivity found in DNA after 180 min of incubation would represent the formation of 0.6-1.0 adducts per 10(6) DNA bases. The results obtained provide evidence for an interaction between lipid peroxidation products and chromatin in the interior of the cell nucleus. 相似文献
14.
Hypobaric hypoxia is known to cause cognitive dysfunctions and memory impairment. The present study aimed at exploring the occurrence of oxidative stress in hypobaric hypoxia and the differential temporal response of the hippocampus, cerebellum following hypobaric hypoxia. Animals were divided into control, 3 days, 7 days and 14 days exposure groups and were exposed to an altitude of 25,000 ft. Our study revealed an increase in lactate dehydrogenase activity along with increase in free radical generation and lipid peroxidation. We also noted depletion in the antioxidants and decrease in glutathione reductase and superoxide dismutase activity. There was significant decrease in reduced glutathione levels in the exposure groups when compared to the control which was accompanied by a concomitant increase in oxidized glutathione levels. Increase in glutamate dehydrogenase activity was observed coinciding with the decrease in glutathione levels which was accompanied with an increase in expression of vesicular glutamate transporter. The hippocampus was found to be more vulnerable to hypobaric hypoxia-induced oxidative stress in comparison to the cortex and cerebellum. An interesting observation was the onset of acclimatization on prolonged exposure to hypobaric hypoxia for a period of 14 days. Hypobaric hypoxia was found to affect various regions of the brain differentially and the response of each region varied as a function of time. 相似文献
15.
Oxidative Damage to Proteins, Lipids, and DNA in Cortical Brain Regions from Patients with Dementia with Lewy Bodies 总被引:10,自引:4,他引:6
Leonidas Lyras Robert H. Perry Elaine K. Perry Paul G. Ince rew Jenner Peter Jenner Barry Halliwell 《Journal of neurochemistry》1998,71(1):302-312
Abstract: Dementia with Lewy bodies (DLB) forms the second most common pathological subgroup of dementia after Alzheimer's disease. The present study compares the levels of oxidative damage to proteins, lipids, and DNA bases in cortical brain areas from patients with DLB with levels in matched control tissues. Overall, there was a trend for protein carbonyl levels to be increased in all areas, but a significant difference was found only in the parietal and temporal lobes. No differences were observed in the levels of lipid peroxidation. Measurement of products of damage to DNA bases showed increased levels of thymine glycol, 8-hydroxyguanine, 2,6-diamino-4-hydroxy-5-formamidopyrimidine, 5-hydroxycytosine, 5-hydroxyuracil, 5-hydroxymethyluracil, and xanthine. Xanthine levels were increased in the DLB group in the parietal, occipital, and temporal lobes, indicating that peroxynitrite or other deaminating species may be involved. The finding of increased protein carbonyls and increased DNA base products in cortical regions from DLB patients indicates that oxidative stress may play a role in DLB. 相似文献
16.
急性低氧暴露小鼠外周血代谢组变化分析 总被引:2,自引:0,他引:2
目的:探讨急性低氧对小鼠外周血代谢组的影响。方法:将14只小鼠随机分为正常组和低氧组。用基础饲料喂养2周后,将低氧组减压至6000m模拟高度停留8h,实验结束后,采集静脉血制备血浆待测。在核磁共振波谱仪进行^1H NMR检测,采用模式识别分析方法处理数据。结果:与正常组相比,低氧组乳酸含量明显增加,肉碱水平明显降低;脂类、丙氨酸、丙酮酸、谷氨酰胺、胆碱、牛磺酸和葡萄糖含量升高,缬氨酸、肛羟丁酸、谷氨酸、甘油、甘氨酸和丝氨酸含量下降。结论:急性低氧暴露使小鼠血浆碳水化合物、脂肪代谢和氨基酸代谢谱发生变化,表明低氧后能量代谢以及相关物质含量发生改变。 相似文献
17.
Ascorbate-Fe2+-driven lipid peroxidation processes in isolated rat liver nuclei give rise to products that bind to DNA and total nuclear proteins. This has been demonstrated by integrating [3H]arachidonic acid into the nuclear membranes. Lipid peroxidation was estimated from the formation of 2-thiobarbituric acid chromophore, and from the relative distribution of 3H-peroxidation products between the lipidic fraction and the nonlipidic fraction of the nuclear suspensions during incubation. The amount of 3H-peroxidation products associated with DNA and total nuclear proteins increased about threefold, when compared to control experiments (no ascorbate-Fe2+), after 180 min of incubation. In contrast, the radioactivity associated with the histone fraction was observed to decrease during incubation. The positive correlation obtained between the formation of thiobarbituric acid chromophore and the association of radioactivity with DNA and nuclear proteins indicates that the binding processes were dependent on peroxidation of the nuclear membrane lipids. 相似文献
18.
脂质过氧化引起的DNA损伤研究进展 总被引:43,自引:0,他引:43
脂质过氧化可以引起各种碱基损伤、DNA链断裂和各种荧光产物生成,并对DNA分子鸟嘌呤碱基具有选择性损伤.过渡金属离子可以明显加深脂质过氧化对DNA的损伤程度.多种抗氧化剂、活性氧自由基清除剂对脂质过氧化引起的DNA损伤有一定程度的保护作用.具有致突、致癌作用的8-羟基鸟嘌呤已经观察到.脂质过氧化的致突变、致癌变作用机制引起了人们的极大兴趣. 相似文献
19.
Daisuke Yajima Hisako Motani Mutsumi Hayakawa Yayoi Sato Kaoru Sato Hirotaro Iwase 《Cell biochemistry and function》2009,27(6):338-343
We consecutively observed lipid peroxidation and cell membrane damage under the condition of hypoxia‐reoxygenation (H/R) in cells and analyzed their mechanisms by using electron transport inhibitors and an antioxidant. In H/R experiments, lipid peroxidation and cell membrane damage were observed during the hypoxia phase. In the reoxygenation phase, lipid peroxidation stopped, while cell membrane damage did not. An antioxidant, n‐acetylcystein (NAC), and potassium cyanide (KCN) inhibited lipid peroxidation and cell membrane damage, while rotenone did not inhibit either of them. Although antimycin A did not inhibit lipid peroxidation, it inhibited cell membrane damage during the hypoxia phase but not during the reoxygenation phase. These results suggested that lipid peroxidation can affect cell membrane damage as a trigger during the hypoxia phase and the generation of oxidative stress can vary depending on the inhibition locations in the electron transport system. Copyright © 2009 John Wiley & Sons, Ltd. 相似文献
20.
Membrane lipid peroxidation processes yield products that may react with DNA and proteins to cause oxidative modifications. Cytosolic NADP+-dependent isocitrate dehydrogenase (ICDH) in U937 cells produces NADPH, an essential reducing equivalent for the antioxidant system. The protective role of ICDH against lipid peroxidation-mediated oxidative damage in U937 cells was investigated in control cells pre-treated with oxalomalate, a competitive inhibitor of ICDH. Upon exposure to 2,2'-azobis(2-amidinopropane) hydrochloride (AAPH) to U937 cells, which induces lipid peroxidation in membranes, the viability was lower and the protein oxidation, lipid peroxidation, and oxidative DNA damage, reflected by an increase in 8-hydroxy-2'-deoxyguanosine, were higher in oxalomalate-treated cells as compared to control cells. We also observed the significant increase in the endogenous production of reactive oxygen species, as measured by the oxidation of 2',7'-dichlorodihydrofluorescin, as well as the significant decrease in the intracellular GSH level in oxalomalate-treated U937 cells upon exposure to AAPH. These results suggest that ICDH plays an important role as an antioxidant enzyme in cellular defense against lipid peroxidation-mediated oxidative damage through the removal of reactive oxygen species. 相似文献