BACKGROUND & AIMS: :Background and Purpose: Oxidative stress is involved in the development of infections. However, whether oxidative stress indicators can be used as markers of stroke-associated infection (SAI) is still unclear. The purpose of this study was to test the predictive values of superoxide dismutase (SOD) and malondialdehyde (MDA) levels for SAI incidence.Methods: A total of 45 consecutive patients with ischemic stroke who were admitted to our hospital were enrolled. A prospective study was carried out to observe the occurrence of SAI during the first 7 days after stroke. Accordingly, the patients were divided into SAI and non-SAI groups. The relationship between SOD and MDA serum levels and SAI was analyzed.Results: The patients in the SAI group had significantly higher serum SOD levels than those in the non-SAI group (41.638 ± 3.428 U/ml vs. 36.542 ± 9.114 U/ml, p = 0.033). However, there were no significant differences in MDA levels between the SAI and non-SAI group (p > 0.05). The discriminating ability of serum SOD level for SAI was measured using an ROC curve. Serum level of SOD >38.16 U/ml was useful in diagnosing SAI with a sensitivity of 88% and a specificity of 61%. Kaplan-Meier curves showed that the group with serum SOD level >38.16 U/ml had higher rates of SAI incidence (χ2 = 9.688, p = 0.002; log rank test). Furthermore, Cox regression analysis indicated that a serum SOD level >38.16 U/ml was an independent risk factor for SAI (hazard ratio = 5.836; 95% CI, 1.298-26.244; p = 0.021).Conclusions: Acute-phase serum SOD level could be a predictor of SAI.

背景与目标： 背景和目的: 氧化应激参与感染的发展。然而，氧化应激指标是否可以用作卒中相关感染 (SAI) 的标志物仍不清楚。本研究的目的是测试超氧化物歧化酶 (SOD) 和丙二醛 (MDA) 水平对SAI发生率的预测价值。方法: 共纳入我院收治的45例缺血性中风患者。进行了一项前瞻性研究，以观察中风后前7天SAI的发生情况。因此，将患者分为SAI和非SAI组。分析血清SOD和MDA水平与SAI的关系。结果: SAI组患者血清SOD水平明显高于非SAI组 (41.638   ±   3.428  U/ml vs. 36.542   ±   9.114  U/ml，P   =   0.033)。然而，SAI和非SAI组之间的MDA水平没有显着差异 (p  >  0.05)。使用ROC曲线测量血清SOD水平对SAI的区分能力。血清SOD >38.16  U/ml可用于诊断SAI，敏感性为88%，特异性为61%。Kaplan-Meier曲线显示，血清SOD水平> 38.16  U/ml组SAI发生率较高 (χ2   =   9.688，p   =   0.002; log rank检验)。Cox回归分析提示血清SOD> 38.16  U/ml是SAI的独立危险因素 (危险比 = 5.836; 95% CI，1.298-26.244; P   =   0.021)。

BACKGROUND & AIMS: BACKGROUND & OBJECTIVE:There is evidence that reactive oxygen species (ROS) plays an important role in the pathophysiology of many paediatric disorders. We carried out this study to see whether superoxide dismutase (SOD) activity was associated with age, sex and rural or urban status in three groups of Spanish people (newborns, children and young). METHODS:SOD activity was measured in red blood cells in newborns, children and young Spanish people (n=1212, divided in six groups) using the Minami and Yoshikawa method. RESULTS:The newborns had high levels of SOD activity, but among all age groups studied, SOD showed the highest activity in groups 1 and 2. We also observed that this activity decreased gradually with age until achieving adult levels. No significant variations with respect to sex were detected, except for the >or=14 to 18 yr age group, in which SOD activity decreased significantly in females. INTERPRETATION & CONCLUSION:Our findings show that SOD activity in newborns, children and young Spanish people is affected by age but not by gender (except from >or=14-18 yr) or rural or urban status.

背景与目标：

BACKGROUND & AIMS: BACKGROUND AND AIM:Molecular diagnostics and therapeutics of human mesothelioma using disease-related markers present major challenges in clinical practice. To identify biochemical alternations that would be markers of human mesothelioma, we measured the intracellular steady-state levels of biologically important trace metals such as manganese (Mn), copper (Cu), and zinc (Zn) in a human mesothelial cell line, MeT-5A, and in five human mesothelioma cell lines (MSTO-211H, NCI-H226, NCI-H2052, NCI-H2452, ACC-MESO-1) by inductively coupled plasma-mass spectrometry (ICP-MS). We also aimed to investigate whether the alterations were related to the intracellular status of metal-containing superoxide dismutase (SOD). RESULTS:There were no significant differences in the contents of the trace metals among MeT-5A, MSTO-211H, and ACC-MESO-1 cells. However, each of the other three mesothelioma cell lines had a unique characteristic in terms of the intracellular amounts of the metals; NCI-H226 contained an extremely high level of Mn, an amount 7.3-fold higher than that in MeT-5A. NCI-H2052 had significantly higher amounts of Cu (3.4-fold) and Zn (1.3-fold) compared with MeT-5A. NCI-H2452 contained about 5.8-fold the amount of Cu and 2.5-fold that of Mn compared with MeT-5A. As for the intracellular levels of copper/zinc-SOD (Cu/Zn-SOD) and manganese-SOD (Mn-SOD), those of Cu/Zn-SOD were relatively unchanged among the cells tested, and no notable correlation with Cu or Zn contents was observed. On the other hand, all mesothelioma cells highly expressed Mn-SOD compared with MeT-5A, and a very high expression of the enzyme with a robust activity was observed in the two mesothelioma cells (NCI-H226, NCI-H2452) containing a large amount of Mn. CONCLUSIONS:In comparison with MeT-5A human mesothelial cells, some human mesothelioma cells had significantly higher amounts of Mn or Cu and one mesothelioma cell had a significantly higher amount of Zn. Interestingly, all mesothelioma cells overexpressed Mn-SOD compared with MeT-5A, and the cells whose Mn-SOD activity was increased contained higher amounts of Mn. It seemed that intracellular Mn content was positively correlated with Mn-SOD, suggesting that the intracellular Mn level is associated with Mn-SOD activity. These biochemical signatures could be potential disease-related markers of mesothelioma.

背景与目标：

BACKGROUND & AIMS: :A new chloroplastic Cu/Zn-superoxide dismutase (SOD) isoenzyme was identified in Arabidopsis thaliana ecotype Cvi. Genetic analyses indicated that the new isoenzyme was encoded by a Cvi-specific allele of Csd2 that was named Csd2-2. Paraquat treatments of A. thaliana ecotypes Ler and Cvi resulted in higher levels of chloroplastic Cu/Zn-SOD activity in Cvi, suggesting that the Cvi isoenzyme has a higher stability and/or turnover rate than the Ler variant under photo-oxidative conditions. In addition, Cvi showed a higher tolerance to paraquat treatments. Hybrid plant populations expressing Csd2-2 also exhibited an increased tolerance, suggesting that the Cvi isoenzyme is one of the factors that contribute to a better fitness in photo-oxidative stress conditions.

背景与目标： : 在拟南芥生态型Cvi中鉴定出一种新的叶绿体Cu/Zn-超氧化物歧化酶 (SOD) 同工酶。遗传分析表明，新的同工酶由Csd2的Cvi特异性等位基因编码，该等位基因被命名为Csd2-2。百草枯处理拟南芥生态型Ler和Cvi导致Cvi中叶绿体Cu/Zn-SOD活性水平较高，这表明Cvi同工酶在光氧化条件下比Ler变体具有更高的稳定性和/或周转率。此外，Cvi对百草枯治疗表现出更高的耐受性。表达Csd2-2的杂交植物种群也表现出更高的耐受性，这表明Cvi同工酶是有助于在光氧化应激条件下更好适应性的因素之一。

BACKGROUND & AIMS: :Excitotoxic neuronal death is mediated in part by NMDA receptor-induced activation of NOX2, an enzyme that produces superoxide and resultant oxidative stress. It is not known, however, whether the superoxide is generated in the intracellular space, producing oxidative stress in the neurons responding to NMDA receptor activation, or in the extracellular space, producing oxidative stress in neighboring cells. We evaluated these alternatives by preparing cortical neuron cultures from p47(phox-/-) mice, which are unable to form a functional NOX2 complex, and transfecting the cultures at low density with GFP-tagged p47(phox) to reconstitute NOX2 activity in widely scattered neurons. NMDA exposure did not induce oxidative stress or cell death in the nontransfected, p47-phox(-/-) cultures, but did produce oxidative stress and neuronal death in neurons surrounding the transfected, NOX2-competent neurons. This cell-to-cell spread of NMDA-induced oxidative injury was blocked by coincubation with either superoxide dismutase or the anion channel blocker 4'-diisothiocyanostilbene-2,2'-disulphonate, confirming superoxide anion as the mediating oxidant. In neurons plated on a preexisting astrocyte layer, NMDA induced oxidative stress in both the neurons and the astrocytes, and this was also prevented by superoxide dismutase. These findings show that activation of NMDA receptors on one neuron can lead to oxidative stress and cell death in neighboring neurons and astrocytes by a process involving the extracellular release of superoxide by NOX2.

背景与目标： : 兴奋性毒性神经元死亡部分由NMDA受体诱导的NOX2激活介导，NOX2是一种产生超氧化物和由此产生的氧化应激的酶。然而，尚不清楚超氧化物是在细胞内空间产生的，在响应NMDA受体激活的神经元中产生氧化应激，还是在细胞外空间中产生邻近细胞的氧化应激。我们通过从无法形成功能性NOX2复合物的p47(phox-/-) 小鼠中制备皮质神经元培养物，并用GFP标记的p47(phox) 以低密度转染培养物以重建NOX2活性来评估这些替代方案分散的神经元。NMDA暴露不会在未转染的p47-phox(-/-) 培养物中诱导氧化应激或细胞死亡，但确实在转染的NOX2-competent神经元周围的神经元中产生氧化应激和神经元死亡。通过与超氧化物歧化酶或阴离子通道阻滞剂4 '-diisothiocyanostilbene-2，2'-二磺酸盐共孵育来阻断NMDA诱导的氧化损伤的细胞间扩散，确认超氧阴离子为介导氧化剂。在铺在预先存在的星形胶质细胞层上的神经元中，NMDA在神经元和星形胶质细胞中均诱导了氧化应激，超氧化物歧化酶也阻止了氧化应激。这些发现表明，一个神经元上NMDA受体的激活可以通过涉及nox2在细胞外释放超氧化物的过程导致邻近神经元和星形胶质细胞的氧化应激和细胞死亡。

BACKGROUND & AIMS: BACKGROUND:Despite familial clustering of nephropathy and retinopathy severity in type 1 diabetes, few gene variants have been consistently associated with these outcomes. RESEARCH DESIGN AND METHODS:We performed an individual-based genetic association study with time to renal and retinal outcomes in 1,362 white probands with type 1 diabetes from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study. Specifically, we genotyped 1,411 SNPs that capture common variations in 212 candidate genes for long-term complications and analyzed them for association with the time from DCCT baseline to event for renal and retinal outcomes using multivariate Cox proportion hazards models. To address multiple testing and assist interpretation of the results, false discovery rate q values were calculated separately for each outcome. RESULTS:We observed association between rs17880135 in the 3' region of superoxide dismutase 1 (SOD1) and the incidence of both severe nephropathy (hazard ratio [HR] 2.62 [95% CI 1.64-4.18], P = 5.6 x 10(-5), q = 0.06) and persistent microalbuminuria (1.82 [1.29-2.57], P = 6.4 x 10(-4), q = 0.46). Sequencing and fine-mapping identified additional SOD1 variants, including rs202446, rs9974610, and rs204732, which were also associated (P < 10(-3)) with persistent microalbuminuria, whereas rs17880135 and rs17881180 were similarly associated with the development of severe nephropathy. Attempts to replicate the findings in three cross-sectional case-control studies produced equivocal results. We observed no striking differences between risk genotypes in serum SOD activity, serum SOD1 mass, or SOD1 mRNA expression in lymphoblastoid cell lines. CONCLUSIONS:Multiple variations in SOD1 are significantly associated with persistent microalbuminuria and severe nephropathy in the DCCT/EDIC study.

背景与目标：

BACKGROUND & AIMS: :In a search for iron-regulated proteins of Aspergillus nidulans and Aspergillus fumigatus a 16-kDa protein was identified which is about 5-fold upregulated during iron starvation in both species and which can be approximately 500-fold enriched by simple one-step chromatography on Amberlite XAD-16 resin. N-terminal protein sequence analysis and cloning of the respective A. nidulans cDNA identified this protein as a Cu/Zn-superoxide dismutase (SODA). Northern analysis revealed that upregulation of sodA expression occurs at the level of transcript accumulation. This seems to be a specific low iron response and not a general starvation answer since sodA transcript levels do not respond to carbon or nitrogen starvation. In contrast, copper depletion leads to transcriptional downregulation of sodA. Furthermore, sodA expression was found still to be subject to iron regulation in an A. nidulans mutant lacking SREA, a regulator of iron homeostasis, indicating that sodA expression is regulated by an SREA-independent mechanism. The data presented suggest that SODA plays a protective role under iron deplete conditions.

背景与目标： : 在寻找构巢曲霉和烟曲霉的铁调节蛋白时，鉴定出一种16 kDa蛋白，该蛋白在两种物种的铁饥饿期间上调约5倍，并且可以通过简单的一步色谱法富集约500倍在Amberlite XAD-16树脂上。N末端蛋白序列分析和相应的A.Niddulans cDNA的克隆将该蛋白鉴定为Cu/Zn-超氧化物歧化酶 (SODA)。Northern分析表明，苏打表达的上调发生在转录本积累的水平上。这似乎是一种特定的低铁反应，而不是一般的饥饿答案，因为苏打水转录水平对碳或氮的饥饿没有反应。相反，铜的耗竭导致苏打的转录下调。此外，在缺乏铁稳态调节剂SREA的A.Niddulans突变体中，发现苏打表达仍受铁调节，这表明苏打表达受SREA独立机制的调节。提供的数据表明，苏打在铁耗尽条件下起着保护作用。

BACKGROUND & AIMS: BACKGROUND:Diffuse panbronchiolitis (DPB) is characterized by chronic neutrophil-mediated inflammation of the airway mediated by oxygen radical production. DPB can be controlled with low-dose and long-term erythromycin therapy based on its anti-inflammatory effect. OBJECTIVE:In this study, the antioxidant levels were analyzed as an anti-inflammatory effect of erythromycin in the patients. METHODS:We investigated the activity and protein level of an antioxidant enzyme, Cu, Zn-superoxide dismutase (SOD) in alveolar macrophages (AMs) of patients with DPB before and after erythromycin therapy. AMs were obtained from bronchoalveolar lavage fluid. RESULTS:There was no significant difference in the activity of Cu, Zn-SOD between normal subjects and untreated patients. Erythromycin therapy (600 mg/day) significantly increased the activity of the enzyme relative to that before therapy and normal subjects [18.2 units/10(6) cells (9.2-26.2) vs. 4.4 units/10(6) cells (1.1-9.3), p < 0.01 and 10.4 units/10(6) cells (2.4-20.6), p < 0.05, respectively]. Furthermore, the protein level of Cu, Zn-SOD in AMs in treated patients was significantly higher than in the other two groups [69.4 ng/10(6) cells (34.2-147.1) vs. 20.1 ng/ 10(6) cells (16.9-39.8) for untreated patients, p < 0.01 and 43.2 ng/10(6) cells (32.6-68.2) for normal subjects, p < 0.01], but the levels in the latter groups were not different. CONCLUSION:Our results suggest that one of the anti-inflammatory effects of erythromycin in DPB may be, in part, mediated by enhancement of antioxidant activity in AMs.

背景与目标：

BACKGROUND & AIMS: :Cationic fraction III from the lysosomes of normal human peripheral blood polymorphonuclear cells (PMNs) was found to contain superoxide generation enhancing protein (SGEP). Herein, we report on the influence of partially purified SGEP obtained from fraction III (subfractions III-5 and III-6), on various phagocytic functions of human PMNs. SGEP markedly enhanced intracellular bactericidal activity of human peripheral PMNs. The enhancement was time and dose dependent. It also reduced adhesiveness of the PMNs. SGEP did not influence chemotaxis, phagocytosis or phagocytic index. These findings are compatible with our original observation regarding superoxide generation enhancement properties of SGEP.

背景与目标： : 发现正常人外周血多形核细胞 (pmn) 溶酶体中的阳离子级分III含有超氧化物生成增强蛋白 (SGEP)。在本文中，我们报告了从级分III (亚级分III-5和III-6) 获得的部分纯化的SGEP对人pmn的各种吞噬功能的影响。SGEP显着增强了人外周pmn的细胞内杀菌活性。增强是时间和剂量依赖性的。它还降低了pmn的粘附性。SGEP不影响趋化性，吞噬作用或吞噬指数。这些发现与我们关于SGEP的超氧化物生成增强特性的原始观察结果兼容。

BACKGROUND & AIMS: :The phytochemical resveratrol, which is found in grapes and red wine, has been reported to have a variety of biological properties. It was shown in our previous research that introduction of additional hydroxyl groups into the stilbene structure increases the biological activity of resveratrol. In this study, the activity of 3,3',4,4',5,5'-hexahydroxystilbene (M8) was investigated in ZR-75-1, MDA-MB-231 and T47D human breast cancer cells. For evaluation of cytotoxic activity of M8, clonogenic and cell proliferation assays were used. The IC50 values obtained in the clonogenic assay were 0.846 microM for T47D, 8.53 microM for ZR-75-1 cells and 25.5 microM for MDA-MB-231, while IC50 values obtained in the cell proliferation assay were significantly higher: 90.1 microM, 98.4 microM, 127.8 microM for T47D, ZR-75-1 and MDA-MB-231 cells, respectively. Compound M8 caused the activation of caspase-8 in MDA-MB-231 cells (marker of extrinsic apoptotic pathway), while activities of caspase-9 (marker of intrinsic apoptotic pathway) and caspase-3 were increased in all 3 tested cell lines. Activation of caspase-9 and caspase-3 was connected with loss of mitochondrial potential and increase of p53, which could have an impact on downregulation of mitochondrial superoxide dismutase (MnSOD) seen in our experiments. MnSOD is a key enzyme providing antioxidative defense in mitochondria - the cellular center of reactive oxygen species' generation. Downregulation of MnSOD can therefore cause a significant decrease of antioxidant defense in cancer cells. An increase of oxidative stress conditions was suggested by loss of reduced glutathione in tested cells. Since cancer cells are usually under permanent oxidative stress, additional increased ROS generation as a result of the interaction of M8 with the mitochondrial respiratory chain and a decrease in oxidative defense can therefore be a promising method for selective elimination of cancer cells.

背景与目标： : 据报道，在葡萄和红酒中发现的植物化学白藜芦醇具有多种生物学特性。在我们先前的研究中表明，在二苯乙烯结构中引入额外的羟基可以提高白藜芦醇的生物活性。在这项研究中，在ZR-75-1，MDA-MB-231和T47D人乳腺癌细胞中研究了3,3 '，4,4'，5,5 '-六羟基二苯乙烯 (M8) 的活性。为了评估M8的细胞毒性活性，使用了克隆形成和细胞增殖测定法。在克隆形成测定中获得的IC50值为T47D的0.846微m、ZR-75-1细胞的8.53微m和MDA-MB-231的25.5微m，而在细胞增殖测定中获得的IC50值显著更高: 分别为T47D的90.1微m、98.4微m、127.8微m、ZR-75-1和MDA-MB-231细胞。化合物M8引起MDA-MB-231细胞中caspase-8的激活 (外源性凋亡途径的标记)，而caspase-9 (内源性凋亡途径的标记) 和caspase-3的活性在所有3种测试细胞系中均增加。caspase-9和caspase-3的激活与线粒体潜能的丧失和p53的增加有关，这可能对我们实验中看到的线粒体超氧化物歧化酶 (MnSOD) 的下调产生影响。MnSOD是在线粒体中提供抗氧化防御的关键酶-活性氧物种产生的细胞中心。因此，MnSOD的下调会导致癌细胞中抗氧化防御的显着降低。测试细胞中还原型谷胱甘肽的丢失提示氧化应激条件增加。由于癌细胞通常处于永久性氧化应激状态，因此，由于M8与线粒体呼吸链的相互作用以及氧化防御能力的降低，额外增加的ROS生成可能是选择性消除癌细胞的有希望的方法。

BACKGROUND & AIMS: :We have isolated a codominant Arabidopsis mutant, radical-induced cell death1 (rcd1), in which ozone (O(3)) and extracellular superoxide (O(2)(*)-), but not hydrogen peroxide, induce cellular O(2)(*)- accumulation and transient spreading lesions. The cellular O(2)(*)- accumulation is ethylene dependent, occurs ahead of the expanding lesions before visible symptoms appear, and is required for lesion propagation. Exogenous ethylene increased O(2)(*)--dependent cell death, whereas impairment of ethylene perception by norbornadiene in rcd1 or ethylene insensitivity in the ethylene-insensitive mutant ein2 and in the rcd1 ein2 double mutant blocked O(2)(*)- accumulation and lesion propagation. Exogenous methyl jasmonate inhibited propagation of cell death in rcd1. Accordingly, the O(3)-exposed jasmonate-insensitive mutant jar1 displayed spreading cell death and a prolonged O(2)(*)- accumulation pattern. These results suggest that ethylene acts as a promoting factor during the propagation phase of developing oxyradical-dependent lesions, whereas jasmonates have a role in lesion containment. Interaction and balance between these pathways may serve to fine-tune propagation and containment processes, resulting in alternate lesion size and formation kinetics.

背景与目标： : 我们已经分离出一个共显性的拟南芥突变体，自由基诱导的细胞死亡1 (rcd1)，其中臭氧 (O(3)) 和细胞外超氧化物 (O(2)(*)-)，但不是过氧化氢，诱导细胞O(2)(*) 积累和短暂扩散病变。细胞O(2)(*) 的积累是乙烯依赖性的，在可见症状出现之前发生在扩大的病变之前，并且是病变传播所必需的。外源乙烯增加了O(2)(*)-依赖性细胞死亡，而降冰片二烯在rcd1或乙烯不敏感突变体ein2和rcd1 ein2双突变体中的乙烯不敏感性对乙烯感知的损害阻止了O(2)(*)-积累和病变传播。外源茉莉酸甲酯抑制rcd1细胞死亡的传播。因此，暴露于O(3) 的茉莉酸酯不敏感的突变体jar1显示出扩散的细胞死亡和延长的O(2)(*) 积累模式。这些结果表明，在发展为氧自由基依赖性病变的传播阶段，乙烯起促进作用，而茉莉酸酯在病变遏制中起作用。这些途径之间的相互作用和平衡可能有助于微调传播和遏制过程，从而导致交替的病变大小和形成动力学。

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: :Extracellular superoxide dismutase (EC-SOD) is a major superoxide scavenger and may be important to normal vascular function and cardiovascular health. We analyzed family data from 610 healthy Australians to detect and quantify the effects of genes on normal variation in plasma levels of EC-SOD and to test for pleiotropy with plasma nitric oxide (NO) and apolipoprotein A-I (apoA-I). Using maximum-likelihood-based variance decomposition methods, we determined that sex, age, and plasma levels of HDL cholesterol, apoA-I, and creatinine accounted for 38.6% of the variance in plasma EC-SOD levels and that additive genes accounted for 35% (P<0.00002). Multivariate analyses of plasma levels of EC-SOD, NO(x) (a measure of basal NO production), and apoA-I detected significant genetic correlations, indicating pleiotropy between EC-SOD and apoA-I (genetic correlation [rho(G)]=-0.45) and between NO(x) and apoA-I (rho(G)=0.58) but not between EC-SOD and NO(x). Genes shared by EC-SOD and apoA-I account for 20% of the genetic variance and, respectively, 7% and 9% of the phenotypic variance in both traits. Shared genes also account for >33% of the genetic variance and 5% and 15% of the respective phenotypic variance in NO(x) and apoA-I. In healthy individuals, over a third of the variance in EC-SOD plasma levels is due to the additive effects of genes. Some genes influence EC-SOD and apoA-I levels. The same is true of NO(x) and apoA-I but not of EC-SOD and NO(x). These patterns of pleiotropy can guide subsequent attempts to identify the genes and physiological mechanisms underlying them.

背景与目标： : 细胞外超氧化物歧化酶 (ec-sod) 是主要的超氧化物清除剂，可能对正常的血管功能和心血管健康很重要。我们分析了来自610名健康澳大利亚人的家庭数据，以检测和量化基因对血浆ec-sod水平正常变化的影响，并测试血浆一氧化氮 (NO) 和载脂蛋白a-i (apoA-I) 的多效性。使用基于最大似然的方差分解方法，我们确定了性别，年龄和血浆HDL胆固醇，apoA-I和肌酐水平占血浆ec-sod水平方差的38.6%，而加性基因占35% (P<0.00002)。血浆ec-sod，NO(x) (基础NO产生的量度) 和apoa-i的血浆水平的多变量分析检测到显着的遗传相关性，指示ec-sod和apoa-i之间的多效性 (遗传相关性 [rho(G)]=-0.45) 和NO(x) 和apoa-i之间的多效性 (rho(G)= 0.58)，但不是ec-sod和NO(x) 之间的多效性。EC-SOD和apoA-I共有的基因分别占两个性状中遗传变异的20% 以及表型变异的7% 和9%。共享基因还占NO(x) 和apoA-I中遗传变异的> 33% 和各自表型变异的5% 和15%。在健康个体中，ec-sod血浆水平的变化超过三分之一是由于基因的加性作用。一些基因影响EC-SOD和apoA-I水平。NO(x) 和apoA-I也是如此，但EC-SOD和NO(x) 则不是。这些多效性模式可以指导随后尝试鉴定其基础的基因和生理机制。

BACKGROUND & AIMS: :Hydrogen peroxide production in yeast cells undergoing programmed cell death in response to acetic acid occurred in the majority of live cells 15 min after death induction and was no longer detectable after 60 min. Superoxide anion production was found later, 60 and 90 min after death induction when cells viability was 60 and 30%, respectively. In cells protected from death due to acid stress adaptation neither hydrogen peroxide nor superoxide anion could be observed after acetic acid treatment. The early production of hydrogen peroxide in cells in which survival was 100% could play a major role in acetic acid-induced programmed cell death signaling. Superoxide anion is assumed to be generated in cells already en route to acetic acid-induced programmed cell death.

背景与目标： : 在诱导死亡后15分钟，大多数活细胞都发生了对乙酸进行程序性细胞死亡的酵母细胞中过氧化氢的产生，并且在60分钟后不再检测到。当细胞活力分别为60和30% 时，在死亡诱导后60和90分钟发现超氧阴离子产生。在因酸胁迫适应而免于死亡的细胞中，乙酸处理后均未观察到过氧化氢和超氧阴离子。在100% 存活的细胞中早期产生过氧化氢可能在乙酸诱导的程序性细胞死亡信号传导中起主要作用。假定已经在乙酸诱导的程序性细胞死亡途中的细胞中产生了超氧阴离子。

BACKGROUND & AIMS: :The cellular and molecular mechanisms that underlie cardioprotection against I/R by anesthetic-induced preconditioning (APC) require further elucidation. Using isoflurane as a representative anesthetic, we evaluated the hypothesis that APC induces myocardial protection against I/R by attenuation of excessive reactive oxygen species and restoration of mitochondrial bioenergetics through postischemic up-regulation of manganese superoxide dismutase (MnSOD) expression and preservation of respiratory enzyme activity. Pentobarbital anesthetized open-chest Sprague-Dawley rats were subject to 30-min left coronary artery occlusion, followed by 120-min reperfusion. Before ischemia, rats were randomly assigned to receive 0.9% saline, two cycles of brief coronary artery occlusion and reperfusion, or a 30-min exposure to 1.0 minimum alveolar concentration isoflurane in the absence or presence of a specific mitochondrial adenosine triphosphate-sensitive potassium (KATP) channel blocker, 5-hydroxydecanoate; a membrane-permeable superoxide scavenger, 4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl; or a NOS inhibitor, N(G)-nitro-L-arginine methyl ester. Isoflurane exposure induced an initial increase in myocardial superoxide (O2-), but not NO level. It also significantly decreased infarct size and restored mitochondrial respiratory enzyme activity or ATP production in I/R rat hearts, along with suppression of the O2- surge at reperfusion and increase in MnSOD expression or enzyme activity. These protective effects were abrogated by 5-hydroxydecanoate or 4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl, but not by N(G)-nitro-L-arginine methyl ester pretreatment. These results suggest that opening of mitochondrial KATP channel, followed by O2- signaling, induces postischemic augmentation of MnSOD and preservation of mitochondrial respiratory enzyme activities, leading to attenuated cardiac O2- surge and restored ATP production during reperfusion, and underlie APC-induced cardioprotection.

背景与目标： : 麻醉诱导的预处理 (APC) 对I/R心脏保护的细胞和分子机制需要进一步阐明。使用异氟烷作为代表性麻醉剂，我们评估了以下假设: APC通过抑制过多的活性氧种类和线粒体生物能的恢复来诱导心肌对I/R的保护。通过有计划后上调锰超氧化物歧化酶 (MnSOD) 的表达和保留呼吸酶活性。对戊巴比妥麻醉的开胸Sprague-Dawley大鼠进行30分钟的左冠状动脉闭塞，然后进行120分钟的再灌注。缺血前，将大鼠随机分配接受0.9% 生理盐水，两个周期的短暂冠状动脉闭塞和再灌注，或在不存在或存在特定线粒体三磷酸腺苷敏感钾 (KATP) 通道阻滞剂5-羟基癸酸盐的情况下暴露于1.0最低肺泡浓度异氟烷30分钟; 膜可渗透的超氧化物清除剂，4-羟基-2,6，6-四甲基哌啶氧基; 或NOS抑制剂，N(G)-硝基-L-精氨酸甲酯。异氟烷暴露导致心肌超氧化物 (O2-) 的初始增加，但没有水平。它还显着减少了I/R大鼠心脏的梗塞面积并恢复了线粒体呼吸酶活性或ATP产生，并抑制了再灌注时的O2激增并增加了MnSOD表达或酶活性。这些保护作用通过5-羟基癸酸酯或4-羟基-2,6，6-四甲基哌啶氧基消除，但不通过N(G)-硝基-L-精氨酸甲酯预处理消除。这些结果表明，线粒体KATP通道的开放，随后是O2信号传导，可诱导MnSOD的缺血后增强和线粒体呼吸酶活性的保留，从而导致心脏O2激增减弱并在再灌注过程中恢复ATP的产生，并成为APC诱导的心脏保护的基础。