Abstract:
:Gamma-glutamylcysteine synthetase (GCS; also referred to as glutamate-cysteine ligase, GLCL) catalyzes the rate-limiting reaction in glutathione (GSH) biosynthesis. The GCS holoenzyme is composed of a catalytic and regulatory subunit, each encoded by a unique gene. In addition to some conditions which specifically upregulate the catalytic subunit gene, expression of both genes is increased in response to many Phase II enzyme inducers including oxidants, heavy metals, phenolic antioxidants and GSH-conjugating agents. Electrophile Response Elements (EpREs), located in 5'-flanking sequences of both the GCSh and GCSl subunit genes, are hypothesized to at least partially mediate gene induction following xenobiotic exposure. Recent experiments indicate that the bZip transcription factor Nrf2 participates in EpRE-mediated GCS subunit gene activation in combination with other bZip proteins. An AP-1-like binding sequence and an NF-kappaB site have also been implicated in regulation of the catalytic subunit gene following exposure to certain pro-oxidants. Potential signaling mechanisms mediating GCS gene induction by the diverse families of Phase II enzyme inducers include thiol modification of critical regulatory sensor protein(s) and the generation of the reactive oxygen species. This review summarizes recent progress in defining the molecular mechanisms operative in transcriptional control of the genes encoding the two GCS subunits, identifying areas of agreement and controversy. The mechanisms involved in GCS regulation might also be relevant to the transcriptional control of other components of the antioxidant defense battery.
journal_name
Free Radic Resjournal_title
Free radical researchauthors
Wild AC,Mulcahy RTdoi
10.1080/10715760000300291keywords:
subject
Has Abstractpub_date
2000-04-01 00:00:00pages
281-301issue
4eissn
1071-5762issn
1029-2470journal_volume
32pub_type
杂志文章,评审abstract::A range of catechins and oligomeric procyanidins was purified by high performance liquid chromatography (HPLC) from grape seed, apple skin, lentil and almond flesh. Catechins, galloylated epicatechin, glycosylated catechin, procyanidin dimers, galloylated dimers, trimer, and tetramer species were all identified, purif...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.1080/10715769800300391
更新日期:1998-10-01 00:00:00
abstract::Tetrahydrobiopterin (BH4) is a ubiquitous pteridine metabolite that serves as a NOS cofactor. Recently, we showed that BH4 efficiently inhibits superoxide generation from the heme group at the oxygenase domain of eNOS. This role indicates that BH4 acts as a redox switch in the catalytic mechanism of the enzyme, which ...
journal_title:Free radical research
pub_type: 杂志文章,评审
doi:10.1080/1071576021000040655
更新日期:2003-02-01 00:00:00
abstract::The preventive effect of 20(S)-ginsenoside Rg(3) (20(S)-Rg(3)) on lipopolysaccharide (LPS)-induced oxidative tissue injury in rats was investigated in this study. The elevated serum nitrite/nitrate, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase and creatinine levels in LPS-treated control rats were ...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.1080/10715760701581740
更新日期:2007-10-01 00:00:00
abstract::8-OH-deoxyguanosine can diminish the ability of the restriction endonucleases Hpa II and Msp I to cleave DNA. The exact position of the adduct within the recognition site appears to determine the extent of the effect. ...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.3109/10715769509064038
更新日期:1995-09-01 00:00:00
abstract::Generation of toxic oxygen metabolites followed by oxidant- and inflammatory-mediated tissue injury plays a crucial role in the pathogenesis of ischemia and reperfusion (IR). Ubiquinol, the reduced form of coenzyme Q10, is recognized for its potent antioxidant and anti-inflammatory properties in biological membranes. ...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.3109/10715762.2013.858148
更新日期:2014-02-01 00:00:00
abstract::It is well known that reactive oxygen species (ROS) attack several living tissues and increase the risk of development and progression of serious diseases. In neuronal level, ROS induce cell death in concentration-dependent fashion. However, little is known about the mechanisms of neuronal changes by ROS prior to indu...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.3109/10715762.2011.647689
更新日期:2012-02-01 00:00:00
abstract::Hypoxia is a well-known threat to neuronal cells and triggers the pathophysiological syndromes in extreme environments such as high altitudes and traumatic conditions such as stroke. Among several prophylactic molecules proven suitable for ameliorating free radical damage, NAP (an octapeptide with initial amino acids:...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.3109/10715762.2015.1011153
更新日期:2015-04-01 00:00:00
abstract::Previous studies have shown that glucose-6-phosphate dehydrogenase (G6PD)-deficient cells are under increased oxidative stress and undergo premature cellular senescence. The present study demonstrates that G6PD-deficient cells cultured under 3% oxygen concentration had an extended replicative lifespan, as compared wit...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.1080/10715760601184819
更新日期:2007-05-01 00:00:00
abstract::Resorcinols (pentadecylresorcinol, olivetol, orcinol and resorcinol) exhibit antioxidant properties in liposomal systems. Antioxidant potency depends on the length of the alkyl chain. Pentadecylresorcinol has been demonstrated to be the most active antioxidant, indicating significance of its alkyl chain in a lipid bil...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.3109/10715769809070804
更新日期:1998-04-01 00:00:00
abstract::Degenerative diseases such as cancer are induced by oxidative genetic damage. Antioxidants can scavenge reactive oxygen species, but to prevent disease, they must do so quickly, before the DNA bases are damaged. In the present study, a novel method was established for evaluating the potency of antioxidants employing 2...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.1080/10715760290019336
更新日期:2002-03-01 00:00:00
abstract::5-(2,2-dimethyl-1,3-propoxy cyclophosphoryl)-5-methyl-1-pyrroline N-oxide (CYPMPO), a new cyclic DEPMPO-type nitrone was evaluated for spin-trapping capabilities toward hydroxyl and superoxide radicals. CYPMPO is colorless crystalline and freely soluble in water. Both the solid and diluted aqueous solution did not dev...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.1080/10715760600883254
更新日期:2006-11-01 00:00:00
abstract::We investigated the effect of curcumin on liver injury in diabetic rats induced by streptozotocin (STZ) through modulation of endoplasmic reticulum stress (ERS) and unfolded protein response (UPR). Experimental diabetes was induced by a single intraperitoneal injection of STZ (55 mg/kg), and curcumin was given at 100 ...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.3109/10715762.2014.999674
更新日期:2015-03-01 00:00:00
abstract::Prostaglandin E2 (PGE2) has been reported to play critical roles in cell fate decision by interacting with four types of prostanoid receptors such as EP1, EP2, EP3 and EP4. The present study was aimed at investigating the effect of the EP4-specific agonist CAY10598 in human colon cancer HCT116 cells. Our study reveale...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.3109/10715762.2014.951838
更新日期:2014-11-01 00:00:00
abstract::The production of reactive oxygen species, including hydrogen peroxide (H(2)O(2)), is increased in diseased blood vessels. Although H(2)O(2) leads to impairment of the nitric oxide (NO)/soluble guanylate cyclase (sGC)/cGMP signaling pathway, it is not clear whether this reactive molecule affects the redox state of sGC...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.3109/10715762.2015.1089987
更新日期:2015-01-01 00:00:00
abstract::Radicals from one-electron oxidation of 4-hydroxycinnamate, ferulate and 3,4-dihydroxycinnamate have been formed by reaction with the oxidising triplet state of duroquinone. All three compounds react with triplet duroquinone with second order rate constants close to the diffusion-controlled limit. The identity of the ...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.1080/10715760100300621
更新日期:2001-07-01 00:00:00
abstract::To examine local and systemic oxidative status of lung cancer (LC) and oxidant effects of radiotherapy (RT), this study evaluated antioxidants and markers of oxidative and nitrosative stress in bronchoalveolar lavage (BAL) fluid and in the blood of 36 LC patients and 36 non-cancer controls at baseline and during and a...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.1080/10715760902942824
更新日期:2009-07-01 00:00:00
abstract::Lipid peroxidation generates reactive aldehydes, most notably hydroxynonenal (HNE), which covalently binds amino acid residue side chains leading to protein inactivation and insolubility. Specific adducts of lipid peroxidation have been demonstrated to be intimately associated with pathological lesions of Alzheimer's ...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.3109/10715762.2013.794265
更新日期:2013-07-01 00:00:00
abstract::G72 has been characterised as a susceptibility gene that can have wide-ranging effects in a number of neurodegenerative diseases, including schizophrenia and major depression. Indeed, its product, pLG72, is a potential serum biomarker for schizophrenia. Previous transcriptomic and biochemical studies have indicated th...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.1080/10715762.2018.1504293
更新日期:2018-09-01 00:00:00
abstract::Ascorbic acid (vitamin C) induced hydrogen peroxide (H(2)O(2)) formation was measured in household drinking water and metal supplemented Milli-Q water by using the FOX assay. Here we show that ascorbic acid readily induces H(2)O(2) formation in Cu(II) supplemented Milli-Q water and poorly buffered household drinking w...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.1080/10715760500249861
更新日期:2005-11-01 00:00:00
abstract::8-Oxoguanine (8-oxoG) is the most common DNA base modification in the mammalian genome, associated with oxidative stress. Here we analysed the alterations in the distribution of 8-oxoG across the entire murine genome, before and after an elevation of oxidative stress by the use of ferric nitrilotriacetate (Fe-NTA) as ...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.1080/10715762.2020.1733548
更新日期:2020-04-16 00:00:00
abstract::Novel silylated triarylmethyl (TAM) radicals based on TAM core CT-03 and their electron paramagnetic resonance (EPR) spectra are evaluated as a function of oxygen concentration. Combination of peak-to-peak linewidth of the EPR signal and electrochemical determination allows designing a method for oxygen quantification...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.3109/10715762.2014.995183
更新日期:2015-03-01 00:00:00
abstract::Peroxiredoxin 1 (PRDX1) is an antioxidant enzyme that, when secreted, can act as a proinflammatory signal. Here we studied the regulation of intracellular PRDX1 by lipopolysaccharide (LPS) and interferon-gamma (IFN-γ) in the RAW 264.7 mouse macrophage cell line. While LPS or IFN-γ alone did not affect PRDX1 protein le...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.1080/10715762.2019.1637863
更新日期:2019-08-01 00:00:00
abstract:BACKGROUND:The objective of the present study was to determine whether single administration of the antioxidant enzyme bovine superoxide dismutase (bSOD) after radiation therapy (RT) mitigates development of pulmonary toxicity in rats. METHODS:Female F344 rats (n = 60) were divided among six experimental groups: (1) R...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.3109/10715762.2015.1066501
更新日期:2015-10-01 00:00:00
abstract::The aim of this study was to investigate the effect of HDL oxidation on PON1 paraoxonase activity. Also, we were interested in investigating the mechanism by which PON1 could be inactivated and the correlation between its enzymatic activity and the antioxidant properties of HDL. Three different oxidation systems were ...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.1080/1071576021000036614
更新日期:2003-01-01 00:00:00
abstract::Intake of antioxidants from the diet has been recognized to have beneficial health effects, but the potential benefit of taking antioxidants such as β-carotene as supplements is controversial. The aim of the present study was to evaluate the potential protective effects of a physiologically relevant concentration (2 μ...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.3109/10715762.2013.815346
更新日期:2013-09-01 00:00:00
abstract:BACKGROUND AND AIM:Previous studies have shown that preventive treatment with the antioxidant, ebselen, in experimental models of type 1 diabetic nephropathy resulted in an attenuation of structural and functional damage in the kidney. However, evidence for the effectiveness of ebselen in late-intervention studies is l...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.3109/10715762.2014.993628
更新日期:2015-03-01 00:00:00
abstract::Diosgenin possesses anti-inflammatory and anticancer properties. Activated neutrophils produce high concentrations of the superoxide anion which is involved in the pathophysiology of inflammation-related diseases and cancer. In the present study, the inhibitory effect and possible mechanisms of diosgenin on superoxide...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.3109/10715762.2014.966705
更新日期:2014-12-01 00:00:00
abstract::Sublytic levels (microM) of hemin destabilized RBC membrane as indicated by ghost fragmentation pattern using a laser viscodiffractometer. Furthermore, electron microscopic study shows that 5 microM of hemin induced echinocytic transformation whereas higher hemin concentration (40 microM) induced spherocytic transform...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.3109/10715769709097838
更新日期:1997-07-01 00:00:00
abstract::Flavonoids are components of fruit and vegetables that may be beneficial in the prevention of disease such as cancer and cardiovascular diseases. Their beneficial effects will be dependent upon their uptake and disposition in tissues and cells. The metabolism and pharmacokinetics of flavonoids has been an area of acti...
journal_title:Free radical research
pub_type: 杂志文章,评审
doi:10.1080/10715760410001727858
更新日期:2004-08-01 00:00:00
abstract::Nonalcoholic fatty liver disease (NAFLD) is characterised by excessive accumulation of hepatic lipids and oxidative injury of hepatocytes. Scutellarin is a flavonoid glycoside having antioxidative stress activity. Our current study aims to investigate the molecular mechanism of scutellarin ameliorating NAFLD. Scutella...
journal_title:Free radical research
pub_type: 杂志文章
doi:10.1080/10715762.2017.1422602
更新日期:2018-02-01 00:00:00