Abstract:
SIGNIFICANCE:Half a century of research provided unambiguous proof that superoxide and species derived from it-reactive oxygen species (ROS)-play a central role in many diseases and degenerative processes. This stimulated the search for pharmaceutical agents that are capable of preventing oxidative damage, and methods of assessing their therapeutic potential. RECENT ADVANCES:The limitations of superoxide dismutase (SOD) as a therapeutic tool directed attention to small molecules, SOD mimics, that are capable of catalytically scavenging superoxide. Several groups of compounds, based on either metal complexes, including metalloporphyrins, metallocorroles, Mn(II) cyclic polyamines, and Mn(III) salen derivatives, or non-metal based compounds, such as fullerenes, nitrones, and nitroxides, have been developed and studied in vitro and in vivo. Very few entered clinical trials. CRITICAL ISSUES AND FUTURE DIRECTIONS:Development of SOD mimics requires in-depth understanding of their mechanisms of biological action. Elucidation of both molecular features, essential for efficient ROS-scavenging in vivo, and factors limiting the potential side effects requires biologically relevant and, at the same time, relatively simple testing systems. This review discuses the advantages and limitations of genetically engineered SOD-deficient unicellular organisms, Escherichia coli and Saccharomyces cerevisiae as tools for investigating the efficacy and mechanisms of biological actions of SOD mimics. These simple systems allow the scrutiny of the minimal requirements for a functional SOD mimic: the association of a high catalytic activity for superoxide dismutation, low toxicity, and an efficient cellular uptake/biodistribution.
journal_name
Antioxid Redox Signaljournal_title
Antioxidants & redox signalingauthors
Tovmasyan A,Reboucas JS,Benov Ldoi
10.1089/ars.2013.5576subject
Has Abstractpub_date
2014-05-20 00:00:00pages
2416-36issue
15eissn
1523-0864issn
1557-7716journal_volume
20pub_type
杂志文章,评审abstract:SIGNIFICANCE:Ionizing radiation is a vital component in the oncologist's arsenal for the treatment of cancer. Approximately 50% of all cancer patients will receive some form of radiation therapy as part of their treatment regimen. DNA is considered the major cellular target of ionizing radiation and can be damaged dire...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2012.5000
更新日期:2014-04-01 00:00:00
abstract:AIMS:Protein aggregation and oxidative stress are both key pathogenic processes in Parkinson's disease, although the mechanism by which misfolded proteins induce oxidative stress and neuronal death remains unknown. In this study, we describe how aggregation of alpha-synuclein (α-S) from its monomeric form to its solubl...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2015.6343
更新日期:2016-03-01 00:00:00
abstract::Zinc/cysteine coordination environments in proteins are redox-active. Oxidation of the sulfur ligands mobilizes zinc, while reduction of the oxidized ligands enhances zinc binding, providing redox control over the availability of zinc ions. Some zinc proteins are redox sensors, in which zinc release is coupled to conf...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2006.8.1419
更新日期:2006-09-01 00:00:00
abstract::Lipoic acid (LA) and its reduced product dihydrolipoic acid (DHLA) are potent antioxidants with capacity to scavenge reactive oxygen species (ROS) and recycle endogenous antioxidants. LA may increase cellular glutathione (GSH), an antioxidant lacking in the lung's epithelial lining fluid in lung disorders such as idio...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2007.1890
更新日期:2008-02-01 00:00:00
abstract::Since the initial report of nitric oxide (NO) activity, enormous progress has been made over the last two decades in the field of NO research. Whereas most physiological responses triggered by moderate concentrations of NO are mediated by soluble guanylate cyclase activation and the subsequent production of cyclic GMP...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/152308602760598972
更新日期:2002-10-01 00:00:00
abstract::It is well accepted that atherosclerosis occurs in a site-specific manner especially at branch points where disturbed blood flow (d-flow) predisposes to the development of plaques. Investigations both in vivo and in vitro have shown that d-flow is pro-atherogenic by promoting oxidative and inflammatory states in the a...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2010.3679
更新日期:2011-09-01 00:00:00
abstract:SIGNIFICANCE:Lysosomes are organelles in which cellular degradation occurs in a controlled manner, separated from other cellular components. As several pathways terminate in the lysosome, lysosomal dysfunction has a profound impact on cell homeostasis, resulting in manifold pathological situations, including infectious...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2011.4405
更新日期:2012-09-01 00:00:00
abstract:AIMS:The usefulness of estrogen replacement therapy (ERT) in preventing oxidative stress associated with menopause is controversial. We aimed to study if there is a critical time window for effective treatment of the effects of ovariectomy with estrogens at the molecular, metabolic, and cellular level. RESULTS:Our mai...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2012.5112
更新日期:2014-01-10 00:00:00
abstract:AIMS:Recent studies have revealed that autophagy is induced under various disease conditions; however, the role of autophagy in pathological states is controversial. NAD(P)H:quinone oxidoreductase 1 (NQO1) is a highly inducible cytoprotective gene that regulates reactive oxygen species (ROS) generation. In this study,...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2015.6386
更新日期:2016-05-20 00:00:00
abstract::Mice deficient in monoamine oxidase A (MAO A) have increased brain levels of serotonin (5-HT) and norepinephrine and show enhanced aggression. We used MAO A knock-out (KO) mice as a model to study the effect of ginkgo biloba (EGb) on aggression. When EGb was administered to MAO A KO mice, their aggressive behavior in ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/15230860050192242
更新日期:2000-10-01 00:00:00
abstract::Cells oxidize molecules to generate energy and to make the materials to build and support the structures and functions needed for life. However, unwanted oxidations can damage these same structures and impair function. Lipids (the lipids in membranes and lipoproteins) are targets of unwanted oxidations. The primary me...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/152308604773934396
更新日期:2004-06-01 00:00:00
abstract::Anthracyclines are widely used in anticancer protocols, but can induce cardiotoxicity by mechanisms that mainly involve oxidative damage and mitochondrial dysfunction. Radiotherapy (RT) can also impair cardiac function by promoting myocardial fibrosis, microvascular damage, and decreased density of myocardial capillar...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2019.7842
更新日期:2019-11-20 00:00:00
abstract::Although much is known about how TNF-alpha induces apoptosis in the presence of inhibitors of protein synthesis, little is known about how it induces apoptosis without these inhibitors. In this report we investigated temporal sequence of events induced by TNF-alpha in the absence of protein synthesis. Regardless of wh...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2009.3036
更新日期:2010-09-15 00:00:00
abstract::Transforming growth factor-betas (TGF-beta) regulate a wide variety of cellular functions in normal development and are involved in both tissue homeostasis and disease pathogenesis. The regulation of the TGF-beta family of growth factors is unique because they are targeted to the extracellular matrix in a biologically...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2007.1914
更新日期:2008-02-01 00:00:00
abstract:: Significance: Atherosclerotic cardiovascular diseases (ACVDs) continue to be a primary cause of mortality worldwide in adults aged 35-70 years, occurring more often in countries with lower economic development, and they constitute an ever-growing global burden that has a c...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2019.7955
更新日期:2021-01-01 00:00:00
abstract::Hemoglobin is considered a potentially toxic molecule when released from erythrocytes during hemolysis, inflammation, or tissue injury. The mechanisms of toxicity involve reduced nitric oxide bioavailability and oxidative processes both occurring at the heme prosthetic groups. When the endogenous oxidant H(2)O(2) reac...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2009.2826
更新日期:2010-02-01 00:00:00
abstract:SIGNIFICANCE:In bacteria, transcriptional responses to reactive oxygen and nitrogen species (ROS and RNS, respectively) are typically coordinated by regulatory proteins that employ metal centers or reactive thiols to detect the presence of those species. This review is focused on the structure, function and mechanism o...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2012.4533
更新日期:2012-11-01 00:00:00
abstract::The mitogen-activated protein kinases (MAPKs) play a central role in mediating the activation and transcriptional responses of diverse cells, including glia. c-Jun N-terminal kinase (JNK), a member of the MAPK family, is activated by a variety of stress and proinflammatory signals and in turn phosphorylates its downst...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2006.8.903
更新日期:2006-05-01 00:00:00
abstract::The small GTPase rac1 controls actin redistribution to membrane ruffles in fibroblasts and other cell types, as well as the activation of the NADPH oxidase in phagocytes. We explored the possibility that these two processes could be related. We used a replication-deficient adenoviral vector to overexpress the constitu...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.1999.1.1-29
更新日期:1999-04-01 00:00:00
abstract::Hydrogen sulfide (H(2)S) is a gasotransmitter with multifaceted physiological functions, including the regulation of glucose metabolism. Methylglyoxal (MG) is an intermediate of glucose metabolism and plays an important role in the pathogenesis of insulin resistance syndromes. In the present study, we investigated the...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2009.2918
更新日期:2010-05-01 00:00:00
abstract::Ischemia followed by reperfusion is the primary cause of tissue injury and infarction during heart attack and stroke. The initiating stimulus is believed to involve reactive oxygen species that are produced during reperfusion when electron transport resumes in the mitochondria after suppression by ischemia. Programmed...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2006.8.1667
更新日期:2006-09-01 00:00:00
abstract::This work rests on our previous report (J Cereb Blood Flow Metab 30: 1275-1287, 2010) recognizing that glutamate (Glu) oxaloacetate transaminase (GOT) is induced when brain tissue hypoxia is corrected during acute ischemic stroke (AIS). GOT can metabolize Glu into tricarboxylic acid cycle intermediates and may therefo...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2011.3930
更新日期:2011-05-15 00:00:00
abstract:: Aims: Human embryonic stem cell derived-cardiovascular progenitor cells (hESC-CVPCs) are a promising cell source for cardiac repair, while the underlying mechanisms need to be elucidated. We recently observed cardioprotective effects of human pluripotent stem cell (hPSC)-C...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2018.7688
更新日期:2019-08-10 00:00:00
abstract:SIGNIFICANCE:Selenoprotein K (SelK) is an endoplasmic reticulum (ER) membrane protein, and its expression is sensitive to dietary selenium levels. A recently described role for SelK as a cofactor in catalyzing protein palmitoylation reactions provides an important link between low dietary selenium intake and suboptimal...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2015.6375
更新日期:2015-10-01 00:00:00
abstract:AIMS:Recent studies have shown that cigarette smoke (CS)-induced oxidative stress impairs autophagy, resulting in aggresome-formation that correlates with severity of chronic obstructive pulmonary disease (COPD)-emphysema, although the specific step in autophagy pathway that is impaired is unknown. Hence, in this study...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2016.6842
更新日期:2017-07-20 00:00:00
abstract:SIGNIFICANCE:Changes in shear stress associated with alterations in blood flow initiate a signaling cascade that modulates the vascular phenotype. Shear stress is "sensed" by the endothelium via a mechanosensitive complex on the endothelial cell (EC) membrane that has been characterized as a "mechanosome" consisting of...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2013.5624
更新日期:2014-02-20 00:00:00
abstract:SIGNIFICANCE:Currently, calcific aortic valve disease (CAVD) is only treatable through surgical intervention because the specific mechanisms leading to the disease remain unclear. In this review, we explore the forces and structure of the valve, as well as the mechanosensors and downstream signaling in the valve endoth...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2015.6554
更新日期:2016-09-01 00:00:00
abstract:SIGNIFICANCE:The heme-enzyme myeloperoxidase (MPO) is one of the major neutrophil bactericidal proteins and is stored in large amounts inside azurophilic granules of neutrophils. Upon cell activation, MPO is released and extracellular MPO has been detected in a wide range of acute and chronic inflammatory conditions. R...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2012.4783
更新日期:2013-02-20 00:00:00
abstract::The endothelium is essential for the maintenance of vascular homeostasis. Central to this role is the production of endothelium-derived nitric oxide (EDNO), synthesized by the endothelial isoform of nitric oxide synthase (eNOS). Endothelial dysfunction, manifested as impaired EDNO bioactivity, is an important early ev...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2008.2027
更新日期:2008-10-01 00:00:00
abstract::15-Deoxy-Delta(12,14)-prostaglandin-J(2) (15d-PGJ(2)) is a cyclopentenone prostaglandin regarded as antiinflammatory mediator, which can act through peroxisome proliferator-activated receptor-gamma (PPARgamma) or through G protein-coupled surface receptors. It has been demonstrated that 15d-PGJ(2) potently increases t...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2008.2032
更新日期:2008-12-01 00:00:00