Abstract:
: Significance: Unique to the branched-chain aminotransferase (BCAT) proteins is their redox-active CXXC motif. Subjected to post-translational modification by reactive oxygen species and reactive nitrogen species, these proteins have the potential to adopt numerous cellular roles, which may be fundamental to their role in oncogenesis and neurodegenerative diseases. An understanding of the interplay of the redox regulation of BCAT with important cell signaling mechanisms will identify new targets for future therapeutics. Recent Advances: The BCAT proteins have been assigned novel thiol oxidoreductase activity that can accelerate the refolding of proteins, in particular when S-glutathionylated, supporting a chaperone role for BCAT in protein folding. Other metabolic proteins were also shown to have peroxide-mediated redox associations with BCAT, indicating that the cellular function of BCAT is more diverse. Critical Issues: While the role of branched-chain amino acid metabolism and its metabolites has dominated aspects of cancer research, less is known about the role of BCAT. The importance of the CXXC motif in regulating the BCAT activity under hypoxic conditions, a characteristic of tumors, has not been addressed. Understanding how these proteins operate under various cellular redox conditions will become important, in particular with respect to their moonlighting roles. Future Directions: Advances in the quantification of thiols, their measurement, and the manipulation of metabolons that rely on redox-based interactions should accelerate the investigation of the cellular role of moonlighting proteins such as BCAT. Given the importance of cross talk between signaling pathways, research should focus more on these "housekeeping" proteins paying attention to their wider application.
journal_name
Antioxid Redox Signaljournal_title
Antioxidants & redox signalingauthors
Conway MEdoi
10.1089/ars.2020.8118subject
Has Abstractpub_date
2020-08-03 00:00:00eissn
1523-0864issn
1557-7716pub_type
杂志文章abstract::Thiol peroxidases comprise glutathione peroxidases (GPx) and peroxiredoxins (Prx). The enzymes of both families reduce hydroperoxides with thiols by enzyme-substitution mechanisms. H(2)O(2) and organic hydroperoxides are reduced by all thiol peroxidases, most efficiently by SecGPxs, whereas fast peroxynitrite reductio...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2010.3397
更新日期:2011-08-01 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::Hypoxia-inducible factor (HIF) is a transcriptional activator that promotes death or survival in neurons. The regulators and targets of HIF-1alpha-mediated death remain unclear. We found that prodeath effects of HIF-1 are not attributable to an imbalance in HIF-1alpha and HIF-1beta expression. Rather, the synergistic ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2008.2039
更新日期:2008-12-01 00:00:00
abstract:AIMS:To evaluate mechanisms underlying modulation of inflammatory chemokines in primary human keratinocytes (normal human epidermal keratinocytes) and repair-related processes in wound models by plant polyphenols (PPs) with antioxidant and superoxide scavenging properties (verbascoside [Vb], resveratrol [Rv], polydatin...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2011.4053
更新日期:2012-02-15 00:00:00
abstract:SIGNIFICANCE:Therapeutic hypothermia is commonly applied to limit ischemic injury in organ transplantation, during cardiac and brain surgery and after cardiopulmonary resuscitation. In these procedures, the kidneys are particularly at risk for ischemia/reperfusion injury (IRI), likely due to their high rate of metaboli...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2016.6705
更新日期:2017-09-20 00:00:00
abstract::Reactive oxygen species (ROS) such as superoxide anion (O2-*) and hydrogen peroxide (H2O2) can be produced by vascular endothelium and smooth muscle cells under diverse physiological and pathophysiological situations. These species are known to exert various deleterious effects by which they might induce changes in va...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2000.2.2-363
更新日期:2000-07-01 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::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::Intracellular Ca(2+) signaling, and related mechanisms involving inositol 1,4,5-trisphosphate (IP(3)), nitric oxide, and the excitatory neurotransmitter glutamate, play a major role in the regulation of cellular function in the brain. Due to the complex morphology of central neurons, the correct spatiotemporal distrib...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2010.3367
更新日期:2011-04-01 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:: Significance: Genomic instability, a hallmark of cancer, renders cancer cells susceptible to genomic stress from both endogenous and exogenous origins, resulting in the increased tendency to accrue DNA damage, chromosomal instability, or aberrant DNA localization. Apart fr...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2020.8221
更新日期:2020-12-04 00:00:00
abstract:SIGNIFICANCE:Chagas disease (CD) affects several million people in Latin America and is spreading beyond its classical boundaries due to the migration of infected host and insect vectors, HIV co-infection, and blood transfusion. The current therapy is not adequate for treatment of the chronic phase of CD, and new drugs...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2012.4618
更新日期:2013-09-01 00:00:00
abstract:: Aims: Severe acute pancreatitis (AP) is a serious condition without specific treatment. Mitochondrial dysfunction plays a crucial role in the pathogenesis of AP. Irisin, a novel exercise-induced hormone, contributes to many health benefits of physical activity. We and othe...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2019.7731
更新日期:2019-10-10 00:00:00
abstract::It was recently found that age-related changes in SMP30 expression can be modulated by antioxidative action. In the current study, the modulation of SMP30 gene expression was explored by (a) antioxidative calorie restriction (CR), (b) proinflammatory lipopolysaccharide (LPS), in aged rat, (c) oxidative stress promoter...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2006.8.671
更新日期:2006-03-01 00:00:00
abstract::Vitamin K epoxide, a by-product of the carboxylation of blood coagulation factors, is reduced to vitamin K by an enzymatic system possessing vitamin K epoxide reductase (VKOR) activity. This system is the target of coumarin-derived drugs widely used in thrombosis therapy and prophylaxis. Recently, the key protein of t...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2006.8.347
更新日期:2006-03-01 00:00:00
abstract::Our laboratory demonstrated that hyperhomocysteinemia accelerates atherosclerosis in mouse models through ER stress and activation of the unfolded protein response (UPR). In this study, we tested the hypothesis that homocysteine-induced ER stress may arise from ER-Ca(2+) disequilibria. We found that homocysteine-induc...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2007.1780
更新日期:2007-11-01 00:00:00
abstract:AIMS:Glutathione peroxidase (GPX) mimic ebselen and superoxide dismutase (SOD) mimic copper diisopropylsalicylate (CuDIPs) were used to rescue impaired glucose-stimulated insulin secretion (GSIS) in islets of GPX1 and(or) SOD1-knockout mice. RESULTS:Ebselen improved GSIS in islets of all four tested genotypes. The res...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2013.5361
更新日期:2014-01-10 00:00:00
abstract::Extensive literature exists supporting a role for mitochondrial dysfunction and oxidative damage in the pathogenesis of Alzheimer's disease. Mitochondria are a major source of intracellular reactive oxygen species and are particularly vulnerable to oxidative stress. This review discusses evidence supporting the notion...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2007.1703
更新日期:2007-10-01 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:AIMS:Aberrant Cdk5 (cyclin-dependent kinase 5) and oxidative stress are crucial components of diverse neurodegenerative disorders, including Alzheimer's disease (AD). We previously reported that a change in peroxiredoxin (Prx) expression is associated with protection from neuronal death. The aim of the current study wa...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2016.6810
更新日期:2017-10-10 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:SIGNIFICANCE:Alzheimer's disease is a neurodegenerative disorder that is projected to exceed more than 100 million cases worldwide by 2050. Aging is considered the primary risk factor for some 90% of Alzheimer's cases but a significant 10% of patients suffer from aggressive, early-onset forms of the disease. There is c...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2016.6802
更新日期:2016-12-01 00:00:00
abstract:SIGNIFICANCE:Sessile plants respond to oxidative stress caused by internal and external stimuli by producing diverse forms of enzymatic and nonenzymatic antioxidant molecules. Peroxiredoxins (Prxs) in plants, including the Prx1, Prx5, Prx6, and PrxQ isoforms, constitute a family of antioxidant enzymes and play importan...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2017.7400
更新日期:2018-03-01 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::The signaling networks that mediate activation, proliferation, or programmed cell death of T lymphocytes are dependent on complex redox and metabolic pathways. T lymphocytes are primarily activated through the T-cell receptor and co-stimulatory molecules. Although activation results in lymphokine production, prolifera...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/15230860260196227
更新日期:2002-06-01 00:00:00
abstract::Previous studies identified NADPH oxidases (Nox) and mitochondrial electron transport chain at complex I as major cellular sources of reactive oxygen species (ROS) mediating systemic and cellular responses to intermittent hypoxia (IH). In the present study, we investigated potential interactions between Nox and the mi...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2010.3213
更新日期:2011-02-15 00:00:00
abstract:: Significance: Since the discovery of vascular stem cells, there has been considerable advancement in comprehending the nature and functions of these cells. Due to their differentiation potential to repair endothelial cells and to participate in lesion formation during vasc...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2020.8199
更新日期:2021-01-19 00:00:00
abstract:: Aims: In this study, we investigate the role of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in autoimmune diseases. We focus on oxidative regulation at the interaction between antigen-presenting cells (APCs) and T cells, and consequent effect of ROS a...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2019.7788
更新日期:2020-01-20 00:00:00
abstract::Reactive oxygen species (ROS) generated within the vascular wall trigger low-density lipoprotein (LDL) oxidation, lipid peroxidation, and carbonyl stress that are involved in atherogenesis. We recently reported that the antihypertensive drug, hydralazine, exhibits carbonyl scavenger and antiatherogenic properties, but...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2010.3321
更新日期:2011-06-01 00:00:00
abstract:: Aims: Hemangioendothelioma (HE) may be benign or malignant. Mouse hemangioendothelioma endothelial (EOMA) cells are validated to study mechanisms in HE. This work demonstrates that EOMA cells heavily rely on mitochondria to thrive. Thus, a combination therapy, including we...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2020.8059
更新日期:2021-01-10 00:00:00