Abstract:
SIGNIFICANCE:Glutathione is the most abundant antioxidant molecule in living organisms and has multiple functions. Intracellular glutathione homeostasis, through its synthesis, consumption, and degradation, is an intricately balanced process. Glutathione levels are often high in tumor cells before treatment, and there is a strong correlation between elevated levels of intracellular glutathione/sustained glutathione-mediated redox activity and resistance to pro-oxidant anticancer therapy. Recent Advances: Ample evidence demonstrates that glutathione and glutathione-based systems are particularly relevant in cancer initiation, progression, and the development of anticancer drug resistance. CRITICAL ISSUES:This review highlights the multifaceted roles of glutathione and glutathione-based systems in carcinogenesis, anticancer drug resistance, and clinical applications. FUTURE DIRECTIONS:The evidence summarized here underscores the important role played by glutathione and the glutathione-based systems in carcinogenesis and anticancer drug resistance. Future studies should address mechanistic questions regarding the distinct roles of glutathione in different stages of cancer development and cancer cell death. It will be important to study how metabolic alterations in cancer cells can influence glutathione homeostasis. Sensitive approaches to monitor glutathione dynamics in subcellular compartments will be an indispensible step. Therapeutic perspectives should focus on mechanism-based rational drug combinations that are directed against multiple redox targets using effective, specific, and clinically safe inhibitors. This new strategy is expected to produce a synergistic effect, prevent drug resistance, and diminish doses of single drugs. Antioxid. Redox Signal. 27, 1217-1234.
journal_name
Antioxid Redox Signaljournal_title
Antioxidants & redox signalingauthors
Hatem E,El Banna N,Huang MEdoi
10.1089/ars.2017.7134subject
Has Abstractpub_date
2017-11-20 00:00:00pages
1217-1234issue
15eissn
1523-0864issn
1557-7716journal_volume
27pub_type
杂志文章,评审abstract::DJ-1 is a member of the large and functionally diverse DJ-1/PfpI superfamily and has homologs in nearly all organisms. Because of its connection to parkinsonism and cancer, human DJ-1 has been intensely studied for over a decade. The current view is that DJ-1 is a multifunctional oxidative stress response protein that...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2010.3481
更新日期:2011-07-01 00:00:00
abstract::Nitric oxide (NO) represents a new paradigm for second messengers in regulation. Despite the numerous physiological and pathophysiological functions of NO, its importance as an endogenous second messenger and a cytostatic and/or cytotoxic agent was unknown until 1987. Recent developments in detection methods for endog...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2000.2.4-879
更新日期:2000-01-01 00:00:00
abstract::Studies on thioredoxin (Trx) and its related molecules have expanded dramatically recently. Proteins that share the similar active-site sequence, -Cys-Xxx-Yyy-Cys-, are called the Trx family, and the number of Trx family members is increasing. Trx reductase, which reduces oxidized Trx in cooperation with NADPH, has th...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2005.7.823
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::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:SIGNIFICANCE:Oxidative (reactive oxygen species [ROS]) and nitrosative (reactive nitrogen species [RNS]) stress affects many physiological processes, including survival and death. Although high levels of ROS/RNS mainly causes cell death, low levels of free radicals directly modulate the activities of transcriptional fa...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2013.5746
更新日期:2014-07-01 00:00:00
abstract::Homeostasis within the central nervous system (CNS) is a prerequisite to elicit proper neuronal function. The CNS is tightly sealed from the changeable milieu of the blood stream by the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier (BCSFB). Whereas the BBB is established by specialized endo...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2011.3929
更新日期:2011-09-01 00:00:00
abstract:AIMS:Pancreatic β-cell chronic lipotoxicity evolves from acute free fatty acid (FA)-mediated oxidative stress, unprotected by antioxidant mechanisms. Since mitochondrial uncoupling protein-2 (UCP2) plays antioxidant and insulin-regulating roles in pancreatic β-cells, we tested our hypothesis, that UCP2-mediated uncoupl...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2014.6195
更新日期:2015-10-20 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:SIGNIFICANCE:Ascorbic acid and sodium-dependent vitamin C transporters (SVCT) have been shown to have important functions in the peripheral nervous system (PNS). Ascorbic acid is known to promote myelination in vitro in Schwann cell/dorsal root ganglion co-cultures by the formation of a collagen- and laminin-containing...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2013.5380
更新日期:2013-12-10 00:00:00
abstract::We summarize here our current knowledge about inducible nitric oxide synthase (NOS) activity in human diseases and disorders. As basic research discovers more and more effects of low or high concentrations of NO toward molecular and cellular targets, successful therapies involving inhibition of NO synthesis or applica...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/15230860050192341
更新日期:2000-10-01 00:00:00
abstract:AIMS:Excitotoxicity triggered by extrasynaptic N-methyl-d-aspartate-type glutamate receptors has been implicated in many neurodegenerative conditions, including Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis, and stroke. Mitochondrial calcium overload leading to mitochondrial dysfunction repre...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2017.7092
更新日期:2018-10-20 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:Stiffness of endothelial cells is closely linked to the function of the vasculature as it regulates the release of vasoactive substances such as nitric oxide (NO) and reactive oxygen species. The outer layer of endothelial cells, consisting of the glycocalyx above and the cortical zone beneath the plasma m...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2017.7327
更新日期:2019-03-01 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::Our aim is to deliver an authoritative and challenging perspective of current concepts in plant redox signaling, focusing particularly on the complex interface between the redox and hormone-signaling pathways that allow precise control of plant growth and defense in response to metabolic triggers and environmental con...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2013.5278
更新日期:2013-06-01 00:00:00
abstract::Signal transduction via PI 3-kinases plays an important role in regulating the cellular processes of cell growth, survival, proliferation, and motility. The stimulated generation of reactive oxygen species is a necessary component of the signal transduction mechanisms by which many growth factors and cytokines activat...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2006.8.1765
更新日期:2006-09-01 00:00:00
abstract:AIMS:Carbon monoxide is a respiratory poison and gaseous signaling molecule. Although CO-releasing molecules (CORMs) deliver CO with temporal and spatial specificity in mammals, and are proven antimicrobial agents, we do not understand the modes of CO toxicity. Our aim was to explore the impact of CO gas per se, withou...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2015.6501
更新日期:2016-06-10 00:00:00
abstract:SIGNIFICANCE:A mismatch between energy supply and demand induces tissue hypoxia with the potential to cause cell death and organ failure. Whenever arterial oxygen concentration is reduced, increases in blood flow--hypoxic vasodilation--occur in an attempt to restore oxygen supply. Nitric oxide (NO) is a major signaling...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2012.4979
更新日期:2013-11-10 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::Nox family NADPH oxidases serve a variety of functions requiring reactive oxygen species (ROS) generation, including antimicrobial defense, biosynthetic processes, oxygen sensing, and redox-based cellular signaling. We explored targeting, assembly, and activation of several Nox family oxidases, since ROS production ap...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2009.2637
更新日期:2009-10-01 00:00:00
abstract:: Aims: Clinical use of cisplatin (Cisp), one of the most widely used, common, and effective chemotherapeutic agents, is limited by its side effects, particularly tubular injury-associated nephrotoxicity. Previous studies suggest that hydrogen sulfide (H2S) alleviates Cisp-i...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2019.7728
更新日期:2019-12-01 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::Cerebral amyloid angiopathy (CAA) is frequently observed in Alzheimer's disease (AD) and is characterized by deposition of amyloid beta (Aβ) in leptomeningeal and cortical brain vasculature. In 40% of AD cases, Aβ mainly accumulates in cortical capillaries, a phenomenon referred to as capillary CAA (capCAA). The aim o...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2011.3895
更新日期:2011-09-01 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::Heme oxygenase-1 is the rate-limiting enzyme for the degradation of the prooxidant heme. Previously, we showed that an E-box within the HO-1 promoter is crucial for the regulation of HO-1 expression in primary hepatocytes. Further to investigate the importance of this E-box, we determined the regulatory capacity of th...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2007.1968
更新日期:2008-07-01 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::Through hypoxia-inducible factor 1 (HIF-1), hypoxia regulates the expression of numerous genes and is a potent inducer of angiogenesis. However, interleukin-8 (IL-8), an important angiogenic mediator, has been reported to be downregulated by HIF-1, although the mechanisms have not been elucidated. HIF-1 was induced in...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2008.2211
更新日期:2009-07-01 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