硫氧还蛋白-1在胰腺炎时的表达及其作用

硫氧还蛋白-1(thioredoxin-1,Trx-1)是一种广泛分布的氧化还原蛋白,通过二硫化物活性中心可逆地催化许多氧化还原反应,具有抗氧化和抗炎作用.胰腺炎的病程存在着氧化应激和炎性细胞浸润,Trx-1作为一种内生的抗氧化剂,通过直接清除活性氧发挥抗氧化作用,通过减少致炎细胞因子的表达,发挥间接抗炎、抗氧化作用.重组Trx-1能抑制中性粒细胞浸润,减轻胰腺和肺的炎症,可作为一种新的治疗急性胰腺炎的策略.     

氧化应激与高血压

氧化应激（oxidative stress）：是指机体遭受各种有害刺激时,机体或细胞内自由基的产生和抗氧化防御之间严重失衡,活性氧在机体或细胞内蓄积引起细胞毒性反应,从而导致组织损伤过程。     

氧化应激在类风湿关节炎中的表现

当机体的氧化作用与抗氧化作用失衡并向氧化作用倾斜时,机体产生氧化应激(oxidative stress).氧化应激可促进活性氧簇(reactive oxygen species,ROS)和活性氮簇(reactive nitrogen species,RNS)等的产生[1].产生的活性氧簇和活性氮簇不仅损伤核酸、蛋白质、脂质等生物分子以及线粒体等细胞器,还作为信使分子参与调节基因表达等生理病理过程,进而对细胞或机体组织产生损伤.     

中枢氧化应激对心血管疾病的影响

氧化应激为各种原因导致机体内氧化与抗氧化之间平衡失调,活性氧簇(包括:含氧自由基、脂质过氧化物、超氧化物等)产生过多,而使机体处于促氧化状态。超氧化物对于正常细胞功能是必不可少的。现证实,在非吞噬细胞中由NAD(P)H氧化酶催化所产生的超氧化物(及相关的活性氧簇)对机体健康和疾病的发生发展有很大影响。在中枢神经系统中,过多超氧化物引起的氧化应激会影响心血管中枢稳态进而引发各种心血管疾病。尽管现在已知中枢氧化应激与心力衰竭、高血压等多种心血管疾病密切相关,但对其相关机制却报道甚少,现就此做一综述。     

急性胰腺炎内科治疗的若干进展

CCK受体在急性胰腺炎发病中起重要作用,应用CCK受体拮抗剂能显著抑制胰腺分泌,减轻炎症程度,提高急性胰腺炎生存率。前列腺素能抑制多种外源性与内源性刺激引起的胰腺分泌,并能增加胰腺血流量及具有细胞保护作用。生长抑素及其衍生物不仅能直接或间接地抑制胃肠激素分泌,而且对胰腺实质细胞有直接保护和抑制磷脂酶A_2活性的作用。氧自由基清除剂、血小板活化因子拮抗剂对实验性急性胰腺炎也有显著疗效。     

氧化应激与β2肾上腺素能受体脱敏的关系

氧化应激是体内活性氧和活性氮自由基产生过多,超过了机体清除速率,氧化系统和抗氧化系统失衡,导致活性氧在体内蓄积而引起的分子、细胞和机体的损伤.目前诸多研究认为氧化应激在β2肾上腺素能受体(β2-adrenergic receptor,β2AR)脱敏中起着重要作用,而β2AR脱敏会影响到β2肾上腺素能受体激动剂在支气管哮喘治疗中的效果,现就氧化应激与β2AR脱敏的关系作一综述.     

氧化应激在心血管疾病中的作用

氧化应激(oxidative stress,OS)是指由于氧自由基过量生成和/或细胞内抗氧化防御系统受损,导致氧自由基及其相关代谢产物过量聚集,从而对细胞产生多种毒性作用的病理状态.近年来研究表明,氧化应激是导致心血管系统结构、功能异常的重要原因之一[1],氧化应激以及在氧化应激过程中产生的活性氧与多种心血管疾病的发生发展有着密切关系[2,3].本文就氧化应激在心血管疾病的作用及其相关机制做一综述.     

砷对肝脏的毒性及氧化损伤

砷对肝脏的毒性作用是多方面的,目前认为氧化损伤为一重要机制.环境砷在人体内代谢过程中可产生多种自由基和非自由基产物,引起细胞功能紊乱,直接攻击细胞或诱发脂质过氧化引起机体氧化与抗氧化代谢失衡,造成氧化应激损伤.     

肺的氧化应激及抗氧化剂的干预作用

肺的氧化应激是体内氧化抗氧化平衡失调所致，局部可产生大量的反应性氧化物和反应性氮化物，它们有多种生理作用如调节基因表达和细胞凋亡等，但过度产生时会直接损伤组织并诱发炎症级联反应。抗氧化剂可以通过维持氧化／抗氧化平衡减少肺脏损伤。氧化／抗氧化失衡是许多肺疾病如哮喘、慢性阻塞性肺气肿、急性呼吸窘迫综合征、特发性肺纤维化以及囊性纤维化的病理基础，本文就过度氧化和氧化应激在肺部疾病中作用以及抗氧化剂的干预作一综述。     

氧化应激及抗氧化治疗与支气管哮喘

支气管哮喘(简称哮喘)是一种常见的慢性气道炎症性疾病,氧化应激在其发生发展机制中具有重要的作用。机体受到的氧化应激刺激有内源性和外源性两种途径,通过产生的氧自由基对细胞和分子造成多种形式的损伤。哮喘患者体内氧化水平升高,抗氧化机制降低。研究发现,在哮喘患者或动物模型体内使用一些具有抗氧化作用的物质进行干预可有效预防或拮抗氧化应激损伤,对于哮喘的防治具有重要的意义。     

Antioxidants reduce endoplasmic reticulum stress and improve protein secretion

Protein misfolding in the endoplasmic reticulum (ER) contributes to the pathogenesis of many diseases. Although oxidative stress can disrupt protein folding, how protein misfolding and oxidative stress impact each other has not been explored. We have analyzed expression of coagulation factor VIII (FVIII), the protein deficient in hemophilia A, to elucidate the relationship between protein misfolding and oxidative stress. Newly synthesized FVIII misfolds in the ER lumen, activates the unfolded protein response (UPR), causes oxidative stress, and induces apoptosis in vitro and in vivo in mice. Strikingly, antioxidant treatment reduces UPR activation, oxidative stress, and apoptosis, and increases FVIII secretion in vitro and in vivo. The findings indicate that reactive oxygen species are a signal generated by misfolded protein in the ER that cause UPR activation and cell death. Genetic or chemical intervention to reduce reactive oxygen species improves protein folding and cell survival and may provide an avenue to treat and/or prevent diseases of protein misfolding.     

雌激素与活性氧

大量证据表明活性氧(ROS)对心脑血管疾病的发生和发展有重要影响。它可以直接氧化膜脂质和DNA,造成细胞氧化损伤和异常;同时还作为信使参与细胞各种生理和病理活动,例如调节基因表达和信号转导。近几年,雌激素对心脑血管疾病的保护作用越来越受到人们的重视,它主要参与细胞内的氧化应激反应,但在某些方面也存在争议。     

蛋白质硝基化修饰在组织纤维化中的作用

应激是指机体在感受到各种因素的强烈刺激时,为满足其对应需求,内环境稳态发生的适应性变化与重建.氧化应激是活性氧(ROS)作为主要效应物参与的应激反应,通过氧化作用参与组织与细胞的适应及修复反应,ROS在该过程中可以作为细胞信号转导的第二信使.参与氧化应激的自由基包括ROS和活性氮(RNS).而有RNS参与的应激反应也可...     

Oxidative stress,age-dependent [correction of age-related] cell damage and antioxidative mechanisms

Cellular oxidative stress is due to the production of reactive oxygen species (ROS), on the one hand, and weaknesses of the antioxidative defence, on the other. This is particularly true for cells with an active metabolism such as neurons and muscle cells, but it is also relevant for all other cell types. Hydrogen peroxide is an important member of ROS and is generated predominantly by mitochondria. In combination with reduced trace metals such as iron or copper, hydrogen peroxide is transformed into the highly reactive hydroxyl radical which causes damage to virtually all macromolecules. Oxidation of nucleic acids results in mutations while protein denaturation leads to enzyme defects and impairment of the cytoskeleton. Lipid peroxidation in cell membranes is strongly involved in the perturbation of ion homeostasis. Because this cell damage ultimatively causes cell death, oxidative stress initiates several diseases. Mitochondria play a major role in this context because they are the main source of endogenous oxidative stress and additionally function as an inducer of programmed cell death (apoptosis). Several strategies of antioxidative defence exist: While transition metals can be inactivated by chelating proteins (e.g., ferritin), ROS can be reduced enzymatically (e.g., by the glutathione peroxidase) or non-enzymatically by antioxidants (e.g., by vitamin E, vitamin C and glutathione). Stress proteins are implicated in the repair and transport of denatured proteins as well as in the inhibition of apoptosis.     

Testing the oxidative stress hypothesis of aging in primate fibroblasts: is there a correlation between species longevity and cellular ROS production?

The present study was conducted to test predictions of the oxidative stress theory of aging assessing reactive oxygen species production and oxidative stress resistance in cultured fibroblasts from 13 primate species ranging in body size from 0.25 to 120 kg and in longevity from 20 to 90 years. We assessed both basal and stress-induced reactive oxygen species production in fibroblasts from five great apes (human, chimpanzee, bonobo, gorilla, and orangutan), four Old World monkeys (baboon, rhesus and crested black macaques, and patas monkey), three New World monkeys (common marmoset, red-bellied tamarin, and woolly monkey), and one lemur (ring-tailed lemur). Measurements of cellular MitoSox fluorescence, an indicator of mitochondrial superoxide (O2(·-)) generation, showed an inverse correlation between longevity and steady state or metabolic stress-induced mitochondrial O2(·-) production, but this correlation was lost when the effects of body mass were removed, and the data were analyzed using phylogenetically independent contrasts. Fibroblasts from longer-lived primate species also exhibited superior resistance to H(2)O(2)-induced apoptotic cell death than cells from shorter-living primates. After correction for body mass and lack of phylogenetic independence, this correlation, although still discernible, fell short of significance by regression analysis. Thus, increased longevity in this sample of primates is not causally associated with low cellular reactive oxygen species generation, but further studies are warranted to test the association between increased cellular resistance to oxidative stressor and primate longevity.     

Type 2 diabetes mellitus as a conformational disease

Conformational diseases are conditions that arise from the dysfunctional aggregation of proteins in non-native conformations. Type 2 diabetes mellitus can be defined as a conformational disease because a constituent beta cell protein, islet amyloid polypeptide, undergoes a change in tertiary structure followed by self-association and tissue deposition. Type 2 diabetes mellitus is associated with multiple metabolic derangements that result in the excessive production of reactive oxygen species and oxidative stress. These reactive oxygen species set in motion a host of redox reactions which can result in unstable nitrogen and thiol species that contribute to additional redox stress. The ability of a cell to deal with reactive oxygen species and oxidative stress requires functional chaperones, antioxidant production, protein degradation and a cascade of intracellular events collectively known as the unfolded protein response. It is known that beta cells are particularly susceptible to perturbations in this quality control system and that reactive oxygen species play an important role in the development and/or progression of diabetes mellitus. Oxidative stress and increased insulin production contribute to endoplasmic reticulum stress, protein misfolding, and induction of the unfolded protein response. As the cell's quality control system becomes overwhelmed, conformational changes occur to islet amyloid polypeptide intermediates, generating stable oligomers with an anti-parallel crossed beta-pleated sheet structure that eventually accumulate as space-occupying lesions within the islets. By approaching type 2 diabetes mellitus as a conformational disease in which there is a structural transition from physiological protein to pathological protein, it is possible that the relentless nature of disease progression can be understood in relation to other conformational diseases.     

Pinealon increases cell viability by suppression of free radical levels and activating proliferative processes

The synthetic tripeptide pinealon (Glu-Asp-Arg) demonstrates dose-dependent restriction of reactive oxygen species (ROS) accumulation in cerebellar granule cells, neutrophils, and pheochromocytoma (PC12) cells, induced by oxidative stress stimulated by receptor-dependent or -independent processes. At the same time, pinealon decreases necrotic cell death measured by the propidium iodide test. The protective effect of pinealon is accompanied with a delayed time course of ERK 1/2 activation and modification of the cell cycle. Because restriction of ROS accumulation and cell mortality is saturated at lower concentrations, whereas cell cycle modulation continues at higher concentrations of pinealon, one can conclude that besides its known antioxidant activity, pinealon is able to interact directly with the cell genome.     

Ischemic preconditioning protects hepatocytes via reactive oxygen species derived from Kupffer cells in rats

BACKGROUND AND AIMS: Hepatic ischemic preconditioning decreases sinusoidal endothelial cell injury and Kupffer cell activation after cold ischemia/reperfusion, leading to improved survival of liver transplant recipients in rats. Ischemic preconditioning also protects livers against warm ischemia/reperfusion injury, in which hepatocyte injury is remarkable. We aimed to determine whether ischemic preconditioning directly protects hepatocytes and to elucidate its mechanisms. METHODS: Rats were injected with gadolinium chloride to deplete Kupffer cells or with N -acetyl- l -cysteine, superoxide dismutase, or catalase to scavenge reactive oxygen species. Livers were then preconditioned by 10 minutes of ischemia and 10 minutes of reperfusion. Subsequently, livers were subjected to 40 minutes of warm ischemia and 60 minutes of reperfusion in vivo or in a liver perfusion system. In other rats, livers were preconditioned by H(2)O(2) perfusion instead of ischemia. In the other experiments, livers were perfused with nitro blue tetrazolium to detect reactive oxygen species formation. RESULTS: Ischemic preconditioning decreased injury in hepatocytes, but not in sinusoidal endothelial cells. Kupffer cell depletion itself did not change hepatocyte injury after ischemia/reperfusion, indicating no contribution of Kupffer cells to ischemia/reperfusion injury. However, Kupffer cell depletion reversed hepatoprotection by ischemic preconditioning. Reactive oxygen species formation occurred in Kupffer cells after ischemic preconditioning. Scavenging of reactive oxygen species reversed the effect of ischemic preconditioning, and H(2)O(2) preconditioning mimicked ischemic preconditioning. CONCLUSIONS: Ischemic preconditioning directly protected hepatocytes after warm ischemia/reperfusion, which is not via suppression of changes in sinusoidal cells as in cold ischemia/reperfusion injury. This hepatocyte protection was mediated by reactive oxygen species produced by Kupffer cells.     

Oxidative stress in inflammation-based gastrointestinal tract diseases: challenges and opportunities

Oxygen free radicals in excessively high amounts are all very reactive chemically and can impose a detrimental influence on living organisms by provoking "oxidative stress" that can damage major cellular constituents. The latter includes the cell membrane, cytoplasmic proteins, and nuclear DNA. Conversely, nitric oxide (NO), superoxide anion, and related reactive oxygen species (ROS) when present in low amounts play an important role as regulatory mediators in signaling processes, through which, paradoxically, many ROS-mediated responses can protect the cells against oxidative stress by induction of "redox homeostasis." Therefore, diseases associated with free radical overproduction are provoked by "blazed ROS productions" far beyond the host's capacity to quench. Free radicals have been implicated in the pathogenesis of diverse gastrointestinal (GI) diseases including gastroesophageal reflux disease (GERD), gastritis, enteritis, colitis and associated cancers as well as pancreatitis and liver cirrhosis. This article provides an overview of the role of oxidative stress in inflammation-based GI tract diseases, including reflux esophagitis, Helicobacter pylori-associated gastritis, non-steroidal anti-inflammatory drug-induced enteritis, ulcerative colitis, and associated colorectal cancer. The challenging issue that ROS can contribute to diverse gastrointestinal dysfunction, or manifest dual roles in cancer promotion or cancer suppression will also be discussed for the opportunity to enhance understanding of inflammation-based GI diseases.