Abstract:
:The forkhead box O (FOXO) family of transcription factors regulates a variety of cellular programs, including cell cycle arrest, reactive oxygen species (ROS) scavenging, and apoptosis, and are of key importance in the decision over cell fate. In animal model systems it has been shown that FOXO is involved in the regulation of long lifespan. FOXO activity is tightly controlled by the insulin signaling pathway and by a multitude of ROS-induced posttranslational modifications. In the cell, ROS levels can be sensed by virtue of stimulatory and inhibitory oxidative modification of cysteine residues within proteins that control various signaling cascades. Recently, it was shown that cysteines in FOXO can also act as sensors of the local redox state. In this review we have outlined the cysteine-dependent redox switches that regulate both the insulin and ROS signaling pathways upstream of FOXO. Further, we describe how FOXO controls ROS levels by transcriptional regulation of a multilayered antioxidant system. Finally, we will discuss how cysteine-based redox signaling to FOXO could play a role in fine-tuning the optimal cellular response to ROS to control organismal lifespan.
journal_name
Antioxid Redox Signaljournal_title
Antioxidants & redox signalingauthors
de Keizer PL,Burgering BM,Dansen TBdoi
10.1089/ars.2010.3403subject
Has Abstractpub_date
2011-03-15 00:00:00pages
1093-106issue
6eissn
1523-0864issn
1557-7716journal_volume
14pub_type
杂志文章,评审abstract::An increase of mitochondrial-derived reactive oxygen species (ROS) occurs in nerve growth factor (NGF)-deprived sympathetic neurons undergoing apoptotic death. It has been reported that NGF suppresses increased ROS production by the mitochondria in these cells through a mitogen-activated protein kinase kinase (MEK)/mi...
journal_title:Antioxidants & redox signaling
pub_type: 信件
doi:10.1089/152308603770310301
更新日期:2003-10-01 00:00:00
abstract::The role of free radicals in aging has been a long-standing theory that has now been extended to include both reactive oxygen and nitrogen species. The original concepts that overwhelming oxidative stress depleted antioxidants and thus damaged intracellular targets is being supplanted by the hypothesis that the reacti...
journal_title:Antioxidants & redox signaling
pub_type: 社论
doi:10.1089/15230860050192143
更新日期:2000-10-01 00:00:00
abstract:AIM:Our previous studies have shown that NOD-like receptor protein (NALP3) inflammasome activation is importantly involved in podocyte dysfunction and glomerular sclerosis induced by hyperhomocysteinemia (hHcys). The present study was designed to test whether nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2012.4666
更新日期:2013-05-01 00:00:00
abstract:AIMS:The risk factors promoting acute kidney injury (AKI) to chronic kidney disease (CKD) progression remain largely unknown. The aim of the present study was to investigate whether hyperhomocysteinemia (Hhcy) accelerates the development of renal fibrosis after AKI. RESULTS:Hhcy aggravated ischemia-reperfusion-induced...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2017.7397
更新日期:2019-05-01 00:00:00
abstract:: Aims: Nuclear factor (erythroid-derived 2)-like-2 factor (NRF-2) is a transcription factor well known to provide an advantage for cancer growth and survival regulating the cellular redox pathway. In breast cancer cells, we recently identified the monomeric heme-globin neur...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2019.7870
更新日期:2020-02-01 00:00:00
abstract::We studied the subcellular distribution of mitochondria and superoxide dismutase-1 (SOD1) in whole mounts of microdissected motor axons of rats expressing the ALS-linked SOD1-G93A mutation. The rationale was to determine whether physical interactions between the enzyme and mitochondria were linked to the axonopathy of...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2009.2614
更新日期:2009-07-01 00:00:00
abstract:SIGNIFICANCE:The 3-hydroxy-methylglutaryl coenzyme A reductase inhibitors or statins are important therapeutic agents for lowering serum cholesterol levels. However, recent studies suggest that statins may exert atheroprotective effects beyond cholesterol lowering. These so-called "pleiotropic effects" include effects ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2013.5524
更新日期:2014-03-10 00:00:00
abstract:AIMS:Protein S-glutathionylation, the formation of a mixed disulfide between glutathione and protein thiols, is an oxidative modification that has emerged as a new signaling paradigm, potentially linking oxidative stress to chronic inflammation associated with heart disease, diabetes, cancer, lung disease, and aging. U...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2015.6531
更新日期:2016-11-20 00:00:00
abstract::Trisulfides and other oligosulfides are widely distributed in the biological world. In plants, for example, garlic, trisulfides are associated with potentially beneficial properties. However, an extra neutral sulfur atom covalently bound between the two sulfur atoms of a pair of cysteines is not a common post-translat...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2010.3677
更新日期:2011-07-01 00:00:00
abstract:AIMS:Pharmacological activation of the adaptive response to hypoxia is a therapeutic strategy of growing interest for neurological conditions, including stroke, Huntington's disease, and Parkinson's disease. We screened a drug library with known safety in humans using a hippocampal neuroblast line expressing a reporter...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2013.5595
更新日期:2015-01-10 00:00:00
abstract::Physiological levels of reactive oxygen species (ROS) play an important regulatory role through various signaling transduction pathways in folliculogenesis, oocyte maturation, endometrial cycle, luteolysis, implantation, embryogenesis, and pregnancy. Persistent and elevated generation of ROS leads to a disturbance of ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2007.1964
更新日期:2008-08-01 00:00:00
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 ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2013.5576
更新日期:2014-05-20 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::Hypoxia and its corollaries pose both negative and positive pressures to multicellular eukaryotes. Evolutionarily, life developed under hypoxia, and the building blocks were established under conditions close to anaerobiosis; therefore, reason exists to expect that certain biologic processes may perform preferentially...
journal_title:Antioxidants & redox signaling
pub_type: 社论
doi:10.1089/ars.2007.1730
更新日期:2007-09-01 00:00:00
abstract::Monothiol glutaredoxins (Grxs) with a noncanonical CGFS active site are found in all kingdoms of life. They include members with a single domain and thioredoxin-Grx fusion proteins. In Saccharomyces cerevisiae, the multidomain Grx3 and Grx4 play an essential role in intracellular iron trafficking. This crucial task is...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2010.3811
更新日期:2011-07-01 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::Nuclear factor, erythroid 2 related factor 2 (Nrf2) belongs to the Cap'n'collar/basic region leucine zipper (CNC-bZIP) transcription factor family, and is activated by diverse oxidants, pro-oxidants, antioxidants, and chemopreventive agents. After phosphorylation and dissociation from the cytoplasmic inhibitor, Kelch-...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2006.8.76
更新日期:2006-01-01 00:00:00
abstract::High affinity for NADH, and low affinity for NADPH, for reduction of endogenous coenzyme Q10 (CoQ10) by pig liver plasma membrane is reported in the present work. CoQ reduction in plasma membrane is carried out, in addition to other mechanisms, by plasma membrane coenzyme Q reductase (PMQR). We show that PMQR-catalyze...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2000.2.2-251
更新日期:2000-07-01 00:00:00
abstract::Homocysteine (Hcy) is a redox active thiol-containing compound with pro-oxidant and pathogenic properties in the cardiovascular system. Angiotensin II (Ang II) also plays important roles in age-associated cardiovascular disease. Recently, the GATA4 transcription factor was recognized as a mediator of heart failure. We...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.1999.1.2-233
更新日期:1999-07-01 00:00:00
abstract::The herbicide paraquat (PQ) has been implicated as a potential risk factor for the development of Parkinson's disease. In this study, PQ (0.5-1 microM) was shown to be selectively toxic to dopaminergic (DA) neurons through the activation of microglial NADPH oxidase and the generation of superoxide. Neuron-glia culture...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2005.7.654
更新日期:2005-05-01 00:00:00
abstract::Mitochondrial dynamics and mitophagy are recognized as two critical processes underlying mitochondrial homeostasis. Morphological and bioenergetic characterization of the life cycle of an individual mitochondrion reveals several points where fusion, fission, and mitophagy interact. Mitochondrial fission can produce an...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2010.3779
更新日期:2011-05-15 00:00:00
abstract:SIGNIFICANCE:Many cardiovascular disorders are accompanied by a deregulated cellular redox balance resulting in elevated levels of intracellular reactive oxygen species (ROS). One major antioxidative cellular molecule is thioredoxin-1 (Trx-1). Its indispensability is demonstrated by the embryonic lethality of Trx-1 def...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2012.4822
更新日期:2013-03-20 00:00:00
abstract::Parkinson's disease (PD) is the second most common neurodegenerative disease characterized by selective loss of dopaminergic neurons and the presence of Lewy bodies. The pathogenesis of PD remains incompletely understood. Environmental factors, oxidative damage, misfolded protein aggregates, ubiquitin-proteasome syste...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2006.1524
更新日期:2007-05-01 00:00:00
abstract:AIMS:Adenosine triphosphate (ATP) synthase uses chemiosmotic energy across the inner mitochondrial membrane to convert adenosine diphosphate and orthophosphate into ATP, whereas genetic deletion of Sirt3 decreases mitochondrial ATP levels. Here, we investigate the mechanistic connection between SIRT3 and energy homeost...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2013.5420
更新日期:2014-08-01 00:00:00
abstract::Intestinal detection of nutrients is a crucial step to inform the whole body of the nutritional status. In this paradigm, peripheral information generated by nutrients is transferred to the brain, which in turn controls physiological functions, including glucose metabolism. Here, we investigated the effect of enteric ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2010.3330
更新日期:2011-02-01 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::Protein thiolation is elicited by oxidation by different mechanisms and is involved in a variety of biological processes. Thiols, protein SH (PSH) and non-protein SH groups (NPSH, namely GSH), are in competition in all biological environments in the regulation of oxidant homeostasis because oxidants thiolate proteins,...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2005.7.951
更新日期:2005-07-01 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: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::Heme oxygenase-1 (HO-1) plays a crucial role in tissue pathological changes such as brain injuries. Our previous studies have demonstrated that bradykinin (BK) induces the expression of several inflammatory proteins, including matrix metalloproteinase-9 and COX-2, via mitogen-activated protein kinases and nuclear fact...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2009.2957
更新日期:2010-12-15 00:00:00