Abstract:
AIMS:Cystathionine β-synthase (CBS) catalyzes the first and rate-limiting step in the two-step trans-sulfuration pathway that converts homocysteine to cysteine. It is also one of three major enzymes responsible for the biogenesis of H2S, a signaling molecule. We have previously demonstrated that CBS is activated in cells challenged by oxidative stress, but the underlying molecular mechanism of this regulation has remained unclear. RESULTS:Here, we demonstrate that S-glutathionylation of CBS enhances its activity ∼2-fold in vitro. Loss of this post-translational modification in the presence of dithiothreitol results in reversal to basal activity. Cys346 was identified as the site for S-glutathionylation by a combination of mass spectrometric, mutagenesis, and activity analyses. To test the physiological relevance of S-glutathionylation-dependent regulation of CBS, HEK293 cells were oxidatively challenged with peroxide, which is known to enhance the trans-sulfuration flux. Under these conditions, CBS glutathionylation levels increased and were correlated with a ∼3-fold increase in CBS activity. INNOVATION:Collectively, our results reveal a novel post-translational modification of CBS, that is, glutathionylation, which functions as an allosteric activator under oxidative stress conditions permitting enhanced synthesis of both cysteine and H2S. CONCLUSIONS:Our study elucidates a molecular mechanism for increased cysteine and therefore glutathione, synthesis via glutathionylation of CBS. They also demonstrate the potential for increased H2S production under oxidative stress conditions, particularly in tissues where CBS is a major source of H2S.
journal_name
Antioxid Redox Signaljournal_title
Antioxidants & redox signalingauthors
Niu WN,Yadav PK,Adamec J,Banerjee Rdoi
10.1089/ars.2014.5891subject
Has Abstractpub_date
2015-02-10 00:00:00pages
350-61issue
5eissn
1523-0864issn
1557-7716journal_volume
22pub_type
杂志文章abstract::Studies from many laboratories have shown that overexpression of manganese superoxide dismutase (MnSOD) inhibits the growth of numerous tumor cell types. The inhibition of tumor cell growth can be attributed to the increase in the steady-state levels of H2O2 as a result of the increased dismuting activity of MnSOD. He...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/15230860152409013
更新日期:2001-06-01 00:00:00
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journal_title:Antioxidants & redox signaling
pub_type:
doi:10.1089/ars.2006.8.2175
更新日期:2006-11-01 00:00:00
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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
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journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2013.5373
更新日期:2014-01-20 00:00:00
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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
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journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2007.1816
更新日期:2008-04-01 00:00:00
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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
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journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2018.7721
更新日期:2020-04-10 00:00:00
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journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2005.7.1476
更新日期:2005-11-01 00:00:00
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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
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journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/152308601317203576
更新日期:2001-12-01 00:00:00
abstract::The application of electronic structure methods to the prediction of geometries, spin densities, and hyperfine couplings for biologically relevant quinones and semiquinones is reviewed. It is demonstrated that hybrid-type density functional methods are particularly suitable for such studies. Hydrogen bonding to the se...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/15230860152665000
更新日期:2001-10-01 00:00:00
abstract::Hydrogen sulfide (H(2)S) is a gasotransmitter with multifaceted physiological functions, including the regulation of glucose metabolism. Methylglyoxal (MG) is an intermediate of glucose metabolism and plays an important role in the pathogenesis of insulin resistance syndromes. In the present study, we investigated the...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2009.2918
更新日期:2010-05-01 00:00:00
abstract::Although oxygen is essential for promoting energy metabolism and for enhancing cell proliferation, early mouse embryos are very sensitive to high oxygen concentration. Because the tissue-specificity and sequential changes of the expression of antioxidative enzymes in rodent embryos have not been investigated systemati...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2000.2.4-653
更新日期:2000-01-01 00:00:00
abstract:AIMS:Once dismissed as an inert byproduct of nitric oxide (NO) auto-oxidation, nitrite (NO(2)(-)) is now accepted as an endocrine reservoir of NO that elicits biological responses in major organs. While it is known that tissue nitrite is derived from NO oxidation and the diet, little is known about how nitrite is metab...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2011.4242
更新日期:2012-10-01 00:00:00
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journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2016.6842
更新日期:2017-07-20 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: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: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::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
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journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/152308601317203495
更新日期:2001-12-01 00:00:00
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journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2012.5108
更新日期:2014-02-10 00:00:00
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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::Glutathione peroxidases and thioredoxin reductases are the main selenoproteins expressed by endothelial cells. These enzymes reduce hydroperoxides, their role in endothelial cell physiology, however, by far exceeds prevention of oxidative damage. Reactive oxygen and nitrogen species, especially superoxide, hydroperoxi...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/152308603764816569
更新日期:2003-04-01 00:00:00
abstract::To study early subcellular pathologic changes of tumorigenesis in mouse skin and possible modulation by overexpression of the mitochondrial antioxidant enzyme manganese superoxide dismutase (MnSOD), skin keratinocytes from nontransgenic (Ntg) and transgenic (TgH) mice overexpressing MnSOD topically treated with one do...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/152308604773934297
更新日期:2004-06-01 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::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:Atrial fibrillation (AF) is a burgeoning health-care problem, and the currently available therapeutic armamentarium is barely efficient. Experimental and clinical evidence implicates inflammation and myocardial oxidative stress in the pathogenesis of AF. RECENT ADVANCES:Local and systemic inflammation has...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2013.5542
更新日期:2014-03-10 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::Apoptosis is a highly regulated process essential for the development and homeostasis of multicellular organisms. Whereas caspases, a large family of intracellular cysteine proteases, play central roles in the execution of apoptosis, other proapoptotic and antiapoptotic regulators such as the members of the Bcl-2 fami...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2010.3392
更新日期:2011-08-01 00:00:00