Abstract:
:The DNA base excision-repair pathway is responsible for the repair of DNA damage caused by oxidation/alkylation and protects cells against the effects of endogenous and exogenous agents. Removal of the damaged base creates a baseless (AP) site. AP endonuclease1 (Ape1) acts on this site to continue the BER-pathway repair. Failure to repair baseless sites leads to DNA strand breaks and cytotoxicity. In addition to the repair role of Ape1, it also functions as a major redox-signaling factor to reduce and activate transcription factors such as AP1, p53, HIF-1alpha, and others that control the expression of genes important for cell survival and cancer promotion and progression. Thus, the Ape1 protein interacts with proteins involved in DNA repair, growth-signaling pathways, and pathways involved in tumor promotion and progression. Although knockdown studies with siRNA have been informative in studying the role of Ape1 in both normal and cancer cells, knocking down Ape1 does not reveal the individual role of the redox or repair functions of Ape1. The identification of small-molecule inhibitors of specific Ape1 functions is critical for mechanistic studies and translational applications. Here we discuss small-molecule inhibition of Ape1 redox and its effect on both cancer and endothelial cells.
journal_name
Antioxid Redox Signaljournal_title
Antioxidants & redox signalingauthors
Luo M,Delaplane S,Jiang A,Reed A,He Y,Fishel M,Nyland RL 2nd,Borch RF,Qiao X,Georgiadis MM,Kelley MRdoi
10.1089/ars.2008.2120subject
Has Abstractpub_date
2008-11-01 00:00:00pages
1853-67issue
11eissn
1523-0864issn
1557-7716journal_volume
10pub_type
杂志文章abstract:SIGNIFICANCE:Chronic noncommunicable diseases (NCDs) are the leading causes of disability and death worldwide. NCDs mainly comprise diabetes mellitus, cardiovascular diseases, chronic obstructive pulmonary disease, cancer, and neurological degenerative diseases, which kill more than 80% of population, especially the el...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2017.7427
更新日期:2019-01-20 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::Chronic inflammatory processes induce oxidative stress and lipid peroxidation (LPO), hereby generating DNA-reactive aldehydes such as trans-4-hydroxy-2-nonenal (HNE). Etheno-modified DNA bases are inter alia generated by reaction of DNA with HNE. Using an immunoaffinity-(32)P-postlabeling method, the authors have inve...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2006.8.1003
更新日期:2006-05-01 00:00:00
abstract:: Significance: Excessive and prolonged proinflammatory responses are associated with oxidative stress, which is commonly observed during chronic tuberculosis (TB). Such condition favors tissue destruction and consequently bacterial spread. A tissue remodeling program is als...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2020.8124
更新日期:2021-02-20 00:00:00
abstract::Cyclotides are plant proteins with exceptional stability owing to the presence of a cyclic backbone and three disulfide bonds arranged in a cystine knot motif. Accordingly, they have been proposed as templates to stabilize bioactive epitopes in drug-design applications. The two main subfamilies, referred to as the Möb...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2008.2295
更新日期:2009-05-01 00:00:00
abstract::Peroxisomes are multifunctional organelles with an important role in the generation and decomposition of reactive oxygen species (ROS). In this review, the ROS-producing enzymes, as well as the antioxidative defense system in mammalian peroxisomes, are described. In addition, various conditions leading to disturbances...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2009.2996
更新日期:2010-08-15 00:00:00
abstract:AIMS:Oxidative stress is thought to be involved in Friedreich's ataxia (FRDA), yet it has not been demonstrated in the target neurons that are first to degenerate. Using the YG8R mouse model of FRDA, microarray and neuritic growth experiments were carried out in the dorsal root ganglion (DRG), the primary site of neuro...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2012.4537
更新日期:2013-11-01 00:00:00
abstract:SIGNIFICANCE:Dysregulation of cortical and striatal neuronal processing plays a critical role in Huntington's disease (HD), a dominantly inherited condition that includes a progressive deterioration of cognitive and motor control. Growing evidence indicates that ascorbate (AA), an antioxidant vitamin, is released into ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2013.5387
更新日期:2013-12-10 00:00:00
abstract::The cellular redox state is associated with major cellular processes including differentiation, transformation, and apoptosis. Glutaredoxin 2 (Grx2) is a mitochondrial oxidoreductase suggested to play a critical role in protection against apoptotic stimuli. An alternative Grx2 transcript variant encoding a nonmitochon...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2007.1821
更新日期:2008-03-01 00:00:00
abstract::Accumulating evidence suggests that oxidative stress associated with impaired metabolism of the antioxidant glutathione (GSH) plays a key role in the pathophysiology of schizophrenia. Magnetic resonance spectroscopy (MRS) is one of the brain-imaging techniques that can quantitatively measure bioactive substances such ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2010.3453
更新日期:2011-10-01 00:00:00
abstract:AIMS:The potential receptor for hydrogen sulfide (H2S) remains unknown. RESULTS:H2S could directly activate vascular endothelial growth factor receptor 2 (VEGFR2) and that a small interfering RNA (siRNA)-mediated knockdown of VEGFR2 inhibited H2S-induced migration of human vascular endothelial cells. H2S promoted angi...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2012.4565
更新日期:2013-08-10 00:00:00
abstract::Increased oxidative stress and impaired heat shock protein (HSP) synthesis may contribute to diabetic nephropathy. The question of whether 8-week thiol antioxidant alpha-lipoic acid (LA) supplementation modulates HSP response and oxidative stress was studied in the kidney of streptozotocin-induced diabetic (SID) and n...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2006.1450
更新日期:2007-04-01 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::Homocysteine is a thiol-containing amino acid that has gained notoriety because its elevation in the plasma is correlated with complex and multifactorial diseases, including cardiovascular diseases, neurodegenerative diseases, and neural tube defects. Homocysteine is redox-active, and its toxic effects have been frequ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2005.7.547
更新日期:2005-05-01 00:00:00
abstract:SIGNIFICANCE:Mitochondrial function is central to a wide range of biological processes in health and disease and there is considerable interest in developing small molecules that are taken up by mitochondria and act as either probes of mitochondrial function or therapeutics in vivo. RECENT ADVANCES:Various strategies ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2011.3969
更新日期:2011-12-15 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::Tissue oxygen plays a crucial role in maintaining tissue viability and in various diseases, including responses to therapy. Useful knowledge has been gained by methods that can give limited snapshots of tissue oxygen (e.g., oxygen electrodes) or evidence of a history of tissue hypoxia (e.g., EF5) or even indirect evid...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2007.1635
更新日期:2007-08-01 00:00:00
abstract::Alzheimer's disease (AD) is the most common cause of dementia and a progressive neurodegeneration that appears to result from multiple pathogenic mechanisms (including protein misfolding/aggregation, involved in both amyloid β-dependent senile plaques and tau-dependent neurofibrillary tangles), metabolic and mitochond...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2011.4082
更新日期:2012-05-01 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:AIM:TNF (tumor necrosis factor)-related apoptosis-inducing ligand (TRAIL), is a selective killer of tumor cells, although its potential is limited by the development of resistance. In this article, we investigated whether the polyherbal preparation Zyflamend(®) can sensitize tumor cells to TRAIL. RESULTS:We found that...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2011.3982
更新日期:2012-03-01 00:00:00
abstract::Secretory and transmembrane proteins are correctly folded or processed in the endoplasmic reticulum (ER). Various stresses disturb ER function and provoke the accumulation of unfolded proteins in the ER lumen. This condition is termed ER stress. Recently, ER stress has been linked to neuronal death in various neurodeg...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2006.1520
更新日期:2007-05-01 00:00:00
abstract::Endoplasmic reticulum (ER) stress induces an adaptive program called the unfolded protein response (UPR), which affects activity of an array of kinases and transcription factors. Previous reports provided evidence for activation of nuclear factor-kappaB (NF-kappaB), the major transcription factor regulating inflammato...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2008.2391
更新日期:2009-09-01 00:00:00
abstract::We previously reported a spontaneous development of type 2 diabetes-like phenotypes in glutathione peroxidase-1 (GPX1)-overexpressing (OE) mice. Diet restriction of these mice rescued all their phenotypes, except for hyperinsulinemia and hypersecretion of insulin. This study was to determine whether dietary Se deficie...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2010.3295
更新日期:2011-02-01 00:00:00
abstract::In the brain, the mu-opioid receptor (MOR) activates neural nitric oxide synthase (nNOS) through the PI3K/Akt pathway. The resulting nitric oxide (NO) enhances the function of the glutamate N-methyl-d-aspartate receptor (NMDAR)/calcium and calmodulin-dependent serine/threonine kinase (CaMKII), which subsequently dimin...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2010.3511
更新日期:2011-06-15 00:00:00
abstract::Despite the significance of redox post-translational modifications (PTMs) in regulating diverse signal transduction pathways, the enzymatic systems that catalyze reversible and specific oxidative or reductive modifications have yet to be firmly established. Thioredoxin 1 (Trx1) is a conserved antioxidant protein that ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2010.3831
更新日期:2011-11-01 00:00:00
abstract:SIGNIFICANCE:Redox signaling is a common mechanism in the cellular response toward a variety of stimuli. For analyzing redox-dependent specific alterations in a cell, genetically encoded biosensors were highly instrumental in the past. To advance the knowledge about the importance of this signaling mechanism in vivo, m...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2017.7469
更新日期:2018-08-20 00:00:00
abstract:AIMS:Cigarette smoke (CS)-mediated acquired cystic fibrosis transmembrane conductance regulator (CFTR)-dysfunction, autophagy-impairment, and resulting inflammatory-oxidative/nitrosative stress leads to chronic obstructive pulmonary disease (COPD)-emphysema pathogenesis. Moreover, nitric oxide (NO) signaling regulates ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2016.6895
更新日期:2017-09-01 00:00:00
abstract:SIGNIFICANCE:The rising global prevalence of diabetes and its debilitating complications give rise to significant disability and premature mortality. Due to the silent nature of diabetes and its vascular complications, and limitations in current methods for detection, there is a need for novel biomarkers for early dete...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2017.7318
更新日期:2018-10-10 00:00:00
abstract::Oxidative stress and inflammation are each implicated independently in the development and progression of heart failure. Their interaction, however, is also evident throughout the process from initial injury to cardiac remodeling and failure. In the failing heart, the linkage between excessive reactive oxygen species ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2009.2930
更新日期:2010-10-01 00:00:00
abstract:AIM:The present study was designed to explore the effects of hydrogen sulfide (H2S) on Ca(2+) homeostasis in rat pancreatic acini. RESULTS:Sodium hydrosulfide (NaHS; an H2S donor) induced a biphasic increase in the intracellular Ca(2+) concentration ([Ca(2+)]i) in a dose-dependent manner. The NaHS-induced [Ca(2+)]i el...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2012.5108
更新日期:2014-02-10 00:00:00