Abstract:
:Hemoglobin is considered a potentially toxic molecule when released from erythrocytes during hemolysis, inflammation, or tissue injury. The mechanisms of toxicity involve reduced nitric oxide bioavailability and oxidative processes both occurring at the heme prosthetic groups. When the endogenous oxidant H(2)O(2) reacts with Hb, transient radicals are generated during the peroxidative consumption of H(2)O(2). If not neutralized, these radicals can lead to tissue toxicity. The net biologic effect of extracellular Hb in an H(2)O(2)-rich environment will therefore be determined by the balance of H(2)O(2) decomposition (potential protective effect) and radical generation (potential damaging effect). Here we show that Hb can protect different cell types from H(2)O(2)-mediated cell death and the associated depletion of intracellular glutathione and ATP. Importantly, Hb blunts the transcriptional oxidative-stress response induced by H(2)O(2) in human vascular smooth muscle cells (VSMCs). Based on spectrophotometric and quantitative mass spectrometry analysis, we suggested a novel mechanism in which Hb redox-cycles H(2)O(2) and simultaneously internalizes the radical burden, with irreversible structural globin changes starting with specific amino acid oxidation involving the heme proximate betaCys93 and ultimately ending with protein precipitation. Our results suggest that complex interactions determine whether extracellular Hb, under certain circumstances, acts a protective or a damaging factor during peroxidative stress conditions.
journal_name
Antioxid Redox Signaljournal_title
Antioxidants & redox signalingauthors
Widmer CC,Pereira CP,Gehrig P,Vallelian F,Schoedon G,Buehler PW,Schaer DJdoi
10.1089/ars.2009.2826subject
Has Abstractpub_date
2010-02-01 00:00:00pages
185-98issue
2eissn
1523-0864issn
1557-7716journal_volume
12pub_type
杂志文章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
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journal_title:Antioxidants & redox signaling
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journal_title:Antioxidants & redox signaling
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journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
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更新日期:2010-06-15 00:00:00
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journal_title:Antioxidants & redox signaling
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journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
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journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
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journal_title:Antioxidants & redox signaling
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doi:10.1089/ars.2013.5595
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journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
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journal_title:Antioxidants & redox signaling
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更新日期:2001-06-01 00:00:00
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journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2012.4595
更新日期:2012-12-01 00:00:00
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journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2012.5142
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,评审
doi:10.1089/ars.2013.5566
更新日期:2014-06-20 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
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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
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journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2010.3367
更新日期:2011-04-01 00:00:00
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journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/15230860152542989
更新日期:2001-08-01 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.2018.7688
更新日期:2019-08-10 00:00:00
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journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2010.3098
更新日期:2010-10-01 00:00:00
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journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2018.7614
更新日期:2019-12-20 00:00:00
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journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2007.1546
更新日期:2007-06-01 00:00:00
abstract:AIMS:Protein aggregation and oxidative stress are both key pathogenic processes in Parkinson's disease, although the mechanism by which misfolded proteins induce oxidative stress and neuronal death remains unknown. In this study, we describe how aggregation of alpha-synuclein (α-S) from its monomeric form to its solubl...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2015.6343
更新日期:2016-03-01 00:00:00
abstract:SIGNIFICANCE:Ewan Cameron reported that ascorbate, given orally and intravenously at doses of up to 10 g/day, was effective in the treatment of cancer. Double-blind placebo-controlled clinical trials showed no survival advantage when the same doses of ascorbate were given orally, leading the medical and scientific comm...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
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更新日期:2013-12-10 00:00:00
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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
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journal_title:Antioxidants & redox signaling
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更新日期:2005-05-01 00:00:00
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journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
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更新日期:2020-02-10 00:00:00
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journal_title:Antioxidants & redox signaling
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更新日期:2014-11-10 00:00:00
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journal_title:Antioxidants & redox signaling
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更新日期:2020-11-23 00:00:00
abstract::Autophagy is a bulk degradation process in which cytosolic proteins and organelles are degraded through lysosomes. To evaluate autophagic flux in cardiac myocytes, we generated adenovirus and cardiac-specific transgenic mice harboring tandem fluorescent mRFP-GFP-LC3. Starvation significantly increased the number of mR...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
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更新日期:2011-06-01 00:00:00