Abstract:
INTRODUCTION:Glycating stress can occur together with oxidative stress during neurodegeneration and contribute to the pathogenic mechanism. Nerve growth factor (NGF) accumulates in several neurodegenerative diseases. Besides promoting survival, NGF can paradoxically induce cell death by signaling through the p75 neurotrophin receptor (p75NTR). The ability of NGF to induce cell death is increased by nitration of its tyrosine residues under conditions associated with increased peroxynitrite formation. AIMS:Here we investigated whether glycation also changes the ability of NGF to induce cell death and assessed the ability of post-translational modified NGF to signal through the receptor for advanced glycation end products (RAGEs). We also explored the potential role of RAGE-p75NTR interaction in the motor neuron death occurring in amyotrophic lateral sclerosis (ALS) models. RESULTS:Glycation promoted NGF oligomerization and ultimately allowed the modified neurotrophin to signal through RAGE and p75NTR to induce motor neuron death at low physiological concentrations. A similar mechanism was observed for nitrated NGF. We provide evidence for the interaction of RAGE with p75NTR at the cell surface. Moreover, we observed that post-translational modified NGF was present in the spinal cord of an ALS mouse model. In addition, NGF signaling through RAGE and p75NTR was involved in astrocyte-mediated motor neuron toxicity, a pathogenic feature of ALS. INNOVATION:Oxidative modifications occurring under stress conditions can enhance the ability of mature NGF to induce neuronal death at physiologically relevant concentrations, and RAGE is a new p75NTR coreceptor contributing to this pathway. CONCLUSION:Our results indicate that NGF-RAGE/p75NTR signaling may be a therapeutic target in ALS. Antioxid. Redox Signal. 28, 1587-1602.
journal_name
Antioxid Redox Signaljournal_title
Antioxidants & redox signalingauthors
Kim MJ,Vargas MR,Harlan BA,Killoy KM,Ball LE,Comte-Walters S,Gooz M,Yamamoto Y,Beckman JS,Barbeito L,Pehar Mdoi
10.1089/ars.2016.6966subject
Has Abstractpub_date
2018-06-20 00:00:00pages
1587-1602issue
18eissn
1523-0864issn
1557-7716journal_volume
28pub_type
杂志文章abstract:AIMS:Peroxiredoxins (Prxs) are ubiquitous cysteine-based peroxidases involved in oxidant defense and signal transduction. Despite much study, the precise roles of conserved residues remain poorly defined. In this study, we carried out extensive functional and structural characterization of 10 variants of such residues ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2016.6922
更新日期:2018-03-01 00:00:00
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 repa...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2008.2120
更新日期:2008-11-01 00:00:00
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...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2020.8118
更新日期:2020-08-03 00:00:00
abstract:SIGNIFICANCE:Cystic fibrosis (CF) is the most common lethal genetic disorder in the Caucasian people. It is due to the mutation of cystic fibrosis transmembrane conductance regulator (CFTR) gene located on the long arm of the chromosome 7, which encodes for CFTR protein. The latter, an adenosine triphosphate binding ca...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2014.6012
更新日期:2015-03-01 00:00:00
abstract::The mechanism for regeneration of the active-site "peroxidatic" cysteine in 1-Cys peroxiredoxins is a matter of debate. Saccharomyces cerevisiae Prx1 is a mitochondrial enzyme belonging to the 1-Cys Prx, whereas Grx2 is involved in antioxidant defense and localizes at the mitochondria, so we hypothesized that it could...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2009.2950
更新日期:2010-08-01 00:00:00
abstract::Aging is associated not only with oxidant stress, but also with increased interleukin-6 (IL-6) levels. To determine if oxidative stress could contribute to the age-associated increase IL-6 expression, we exposed LNCaP prostate carcinoma cells and HeLa cervical carcinoma cells to H2O2 as an oxidant challenge. We found ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/15230860152409121
更新日期:2001-06-01 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:The thioredoxin (Trx) superfamily proteins, including protein disulfide isomerases (PDI) and Dsb protein family, are major players in oxidative protein folding, which involves native disulfide bond formation. These proteins contain Trx folds with CXXC active sites and fulfill their physiological functions ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2014.5849
更新日期:2014-07-20 00:00:00
abstract::Tumor necrosis factor (TNF) induces a caspase-independent but mitochondria-dependent cell death process in the mouse fibrosarcoma cell line L929. Mitochondria actively participate in this TNF-induced necrotic cell death by the generation of mitochondrial reactive oxygen species (ROS). The aim of this study was to iden...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.1999.1.3-285
更新日期:1999-10-01 00:00:00
abstract::The possibility of a plasma oxygen diffusion barrier implies a significant resistance to oxygen diffusion and the existence of capillary erythrocyte-associated transients of oxygen. This effect was analyzed by measuring intracapillary blood and tissue pO(2) in the hamster chamber window model using a noninvasive intra...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2007.1584
更新日期:2007-07-01 00:00:00
abstract::Selenium (Se) is an essential trace element in mammals that has been shown to exert its function through selenoproteins. Whereas optimal levels of Se in the diet have important health benefits, a recent clinical trial has suggested that supplemental intake of Se above the adequate level potentially may raise the risk ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2010.3526
更新日期:2011-06-15 00:00:00
abstract::Loss of redox homeostasis and formation of excessive free radicals play an important role in the pathogenesis of kidney disease and hypertension. Free radicals such as reactive oxygen species (ROS) are necessary in physiologic processes. However, loss of redox homeostasis contributes to proinflammatory and profibrotic...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2008.2034
更新日期:2008-12-01 00:00:00
abstract::Clinical heart failure has been defined for a long time as a clinical syndrome with symptoms and signs including shortness of breath, cyanosis, ascites, and edema. However, in recent years, with the thought of promoting early diagnosis and heart-failure prevention, the concept of heart failure has often been defined s...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2009.2488
更新日期:2009-08-01 00:00:00
abstract::To test the hypothesis that the inducible nitric oxide synthase (iNOS) is involved in mediating the toll-like receptor 4-dependent effects on the liver in the onset of fructose-induced steatosis, wild-type and iNOS knockout (iNOS(-/-)) mice were either fed tap water or 30% fructose solution for 8 weeks. Chronic consum...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2010.3263
更新日期:2011-06-01 00:00:00
abstract::The ability to couple photosynthetic electron transport and redox poise to plastid gene expression enables plants to respond to environmental conditions and coordinate nuclear and chloroplast activities in order to maintain photosynthetic efficiency. The plastid redox regulatory system serves as a paradigm for underst...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/152308603321223577
更新日期:2003-02-01 00:00:00
abstract:SIGNIFICANCE:Nicotinamide adenine dinucleotide (NAD+) participates in redox reactions and NAD+-dependent signaling processes, which involve the cleavage of NAD+ coupled to posttranslational modifications of proteins or the production of second messengers. Either as a primary cause or as a secondary component of the pat...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2017.7145
更新日期:2018-06-20 00:00:00
abstract::Epithelial to mesenchymal transition (EMT) is a fundamental process, paradigmatic of the concept of cell plasticity, that leads epithelial cells to lose their polarization and specialized junctional structures, to undergo cytoskeleton reorganization, and to acquire morphological and functional features of mesenchymal-...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2009.2737
更新日期:2010-06-15 00:00:00
abstract:SIGNIFICANCE:Studies of sporadic cases, toxin models, and genetic causes of Parkinson's disease suggest that mitochondrial dysfunction may be an early feature of pathogenesis. RECENT ADVANCES:Compelling evidence of a causal relationship between mitochondrial function and disease was found with the identification of se...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2011.4019
更新日期:2012-05-01 00:00:00
abstract:: Significance: Humans cannot synthesize ascorbic acid (AscH2) (vitamin C), so deficiencies in dietary AscH2 cause the life-threatening disease of scurvy and many other diseases. After oral ingestion, plasma AscH2 concentrations are strictly controlled by transporters, which...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2019.7912
更新日期:2020-01-22 00:00:00
abstract::Coenzyme Q10 (CoQ) has long been utilized as a cardioprotective agent in various heart diseases. One of the most important mechanisms by which CoQ exerts cardioprotection is aerobic ATP production as a mobile electron carrier in the mitochondrial electron transfer chain. The ability of CoQ to afford myocardial protect...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/152308601750100588
更新日期:2001-02-01 00:00:00
abstract:AIMS:Cyclic adenosine 3'5'-monophosphate (cAMP) is a universal second messenger that plays an important role in intracellular signal transduction. cAMP is synthesized by adenylate cyclases from adenosine triphosphate and terminated by the phosphodiesterases (PDEs). In the present study, we investigated the role of the ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2017.7041
更新日期:2018-09-01 00:00:00
abstract::Protection of ischemic myocardium is an important unmet need in reperfusion therapy of acute myocardial infarction. Myocardial ischemia and reperfusion induce necrosis and apoptosis in cardiomyocytes. Caspase processing and activation are critical steps in most receptor and nonreceptor pathways of apoptosis. Caspase i...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/152308601750100605
更新日期:2001-02-01 00:00:00
abstract::Peroxiredoxins (Prxs) are a family of peroxidases that reduce peroxides, with a conserved cysteine residue (the peroxidatic Cys) serving as the site of oxidation by peroxides. Peroxides oxidize the peroxidatic Cys-SH to Cys-SOH, which then reacts with another cysteine residue (typically the resolving Cys [C(R)]) to fo...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2010.3393
更新日期:2011-08-01 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: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::Reactive oxygen species (ROS) can directly induce or enhance tumor necrosis factor (TNF)-mediated apoptosis in a number of different cell lines. To test the relevance of intracellular ROS in modulating apoptotic signaling in vivo, we evaluated hepatocellular apoptosis mediated by the TNF or Fas receptor in wild-type a...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/152308602760598873
更新日期:2002-10-01 00:00:00
abstract:AIMS:Expression of the HER2 oncogene in breast cancer is associated with resistance to treatment, and Her2 may regulate bioenergetics. Therefore, we investigated whether disruption of the electron transport chain (ETC) is a viable strategy to eliminate Her2high disease. RESULTS:We demonstrate that Her2high cells and t...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2016.6677
更新日期:2017-01-10 00:00:00
abstract::The decision to remove or refold oxidized, denatured, or misfolded proteins by heat shock protein 70 and its binding partners is critical to determine cell fate under pathophysiological conditions. Overexpression of the ubiquitin ligase C-terminus of HSC70 interacting protein (CHIP) can compensate for failure of other...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2010.3300
更新日期:2011-05-15 00:00:00
abstract:SIGNIFICANCE:The discovery of the oxidoreductase disulfide bond protein A (DsbA) in 1991 opened the way to the unraveling of the pathways of disulfide bond formation in the periplasm of Escherichia coli and other Gram-negative bacteria. Correct oxidative protein folding in the E. coli envelope depends on both the DsbA/...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2012.4864
更新日期:2013-07-01 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