Human mitochondrial peroxiredoxin 5 protects from mitochondrial DNA damages induced by hydrogen peroxide

Banmeyer, Ingrid; Marchand, Cécile; Clippe, André; Knoops, Bernard

doi:10.1016/j.febslet.2005.03.027

Cited by 132 publications

(79 citation statements)

References 41 publications

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“…Free radical balance is maintained by reduction of the superoxide anion to hydrogen peroxidase by superoxide dimutases. The resulting hydrogen peroxide can then be neutralized by various peroxidases, including peroxiredoxin-V (Banmeyer et al, 2005). Reduction in reactive oxygen species contributes to neuroprotection and can reduce the overall stress response.…”

Section: Discussionmentioning

confidence: 99%

EstradiolIn VivoRegulation of Brain Mitochondrial Proteome

Nilsen¹,

Irwin²,

Gallaher³

et al. 2007

J. Neurosci.

161

170

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We used a combined proteomic and functional biochemical approach to determine the overall impact of 17␤-estradiol (E 2 ) on mitochondrial protein expression and function. To elucidate mitochondrial pathways activated by E 2 in brain, two-dimensional (2D) gel electrophoresis was conducted to screen the mitoproteome. Ovariectomized adult female rats were treated with a single injection of E 2 . After 24 h of E 2 exposure, mitochondria were purified from brain and 2D analysis and liquid chromatography-tandem mass spectrometry protein identification were conducted. Results of proteomic analyses indicated that of the 499 protein spots detected by image analysis, a total of 66 protein spots had a twofold or greater change in expression. Of these, 28 proteins were increased in expression after E 2 treatment whereas 38 proteins were decreased in expression relative to control. E 2 regulated key metabolic enzymes including pyruvate dehydrogenase, aconitase, and ATP-synthase. To confirm that E 2 -inducible changes in protein expression translated into functional consequences, we determined the impact of E 2 on the enzymatic activity of the mitochondrial electron transport chain. In vivo, E 2 treatment enhanced brain mitochondrial efficiency as evidenced by increased respiratory control ratio, elevated cytochrome-c oxidase activity and expression while simultaneously reducing free radical generation in brain. Results of these analyses provide insights into E 2 mechanisms of regulating brain mitochondria, which have the potential for sustaining neurological health and prevention of neurodegenerative diseases associated with mitochondrial dysfunction such as Alzheimer's disease.

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Section: Discussionmentioning

confidence: 99%

EstradiolIn VivoRegulation of Brain Mitochondrial Proteome

Nilsen¹,

Irwin²,

Gallaher³

et al. 2007

J. Neurosci.

161

170

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“…mtDNA is particularly susceptible to oxidative damage due to several factors; it is located close to the ROS-generating respiratory chain, it is not covered by histones, and it lacks a strong repair system compared with that of nuclear DNA. [52][53][54] Previous studies have revealed that there are decreased numbers of mitochondria in FECD endothelium, and that activity of cytochrome oxidase, the major respiratory chain enzyme, is decreased in the central area of FECD corneal buttons. 55 Based on our studies, these findings are consistent with oxidative stress-induced mtDNA damage that could lead to loss of integrity of inner mitochondrial membrane potential and apoptotic cell death.…”

Section: Discussionmentioning

confidence: 99%

Evidence of Oxidative Stress in the Pathogenesis of Fuchs Endothelial Corneal Dystrophy

Jurkunas

Bitar

Funaki

et al. 2010

The American Journal of Pathology

266

263

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Fuchs endothelial corneal dystrophy (FECD) is a progressive, blinding disease characterized by corneal endothelial (CE) cell apoptosis. Corneal transplantation is the only measure currently available to restore vision in these patients. Despite the identification of some genetic factors, the pathophysiology of FECD remains unclear. In this study, we observed a decrease in the antioxidant response element-driven antioxidants in FECD corneal endothelium. We further demonstrated that nuclear factor erythroid 2-related factor 2, a transcription factor known to bind the antioxidant response element and activate antioxidant defense, is down-regulated in FECD endothelium. Importantly, we detected significantly higher levels of oxidative DNA damage and apoptosis in FECD endothelium compared with normal controls and pseudophakic bullous keratopathy (iatrogenic CE cell loss) specimens. A marker of oxidative DNA damage, 8-hydroxy-2-deoxyguanosine, colocalized to mitochondria, indicating that the mitochondrial genome is the specific target of oxidative stress in FECD. Oxidative DNA damage was not detected in pseudophakic bullous keratopathy corneas, whereas it colocalized with terminal deoxynucleotidyl transferasemediated dUTP nick-end labeling-positive cells in FECD samples. Ex vivo, oxidative stress caused characteristic morphological changes and apoptosis of CE, suggestive of findings that characterize FECD in vivo. Together, these data suggest that suboptimal nuclear factor erythroid 2-related factor 2-regulated defenses may account for oxidant-antioxidant imbalance in FECD , which in turn leads to oxidative DNA damage and apoptosis. This study provides evidence that oxidative stress plays a key role in FECD pathogenesis. Corneal endothelium (CE) is a monolayer of cells situated in the anterior chamber surface of the cornea; its primary function is to maintain the cornea in a state of deturgescence through sodium-activated ATPase pumping of water, thus, transparency. Fuchs endothelial corneal dystrophy (FECD) is the most common cause of endogenous corneal endothelial degeneration and is characterized by alterations in corneal endothelial cell morphology, progressive loss of CE cells, and concomitant accumulation of extracellular deposits in the basement membrane that eventually lead to corneal edema and opacity. Because CE does not divide in vivo, loss of endothelial cells seen in FECD is permanent. Corneal transplantation is the only treatment modality that can restore lost vision-rendering FECD the second most common cause of corneal transplants performed on the elderly (Ͼ60 years old) in the United States.2 Lack of knowledge of the mechanism of CE degeneration in FECD precludes the development of pharmacotherapeutics for this common and blinding condition.FECD has been termed a disorder of aging; it is a bilateral and slowly progressive disorder, typically appearing after the age of 60 years. FECD is usually a sporadic condition, but it can be inherited as an autosomal dominant trait.3-5 FECD is characterized by endo...

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“…As antioxidant defense system, Peroxiredoxin (Prx) 3, Prx5, superoxide dismutase 2, and thioredoxin 2 eliminates ROS produced in mitochondria [30,31] . Knockout (KO) of Prx3 mice result in induction of oxidative damage [32] , KO of thioredoxin 2 mice showed an embryonic lethal phenotype [33] and KO of superoxide dismutase 2 mice die within 3 wk of birth because of mitochondrial into the matrix of mitochondria.…”

Section: Mitochondrial Antioxidant Systemmentioning

confidence: 99%

Mitochondria as therapeutic targets for cancer stem cells

Song¹,

Jeong²,

Jeong³

et al. 2015

WJSC

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Cancer stem cells (CSCs) are maintained by their somatic stem cells and are responsible for tumor initiation, chemoresistance, and metastasis. Evidence for the CSCs existence has been reported for a number of human cancers. The CSC mitochondria have been shown recently to be an important target for cancer treatment, but clinical significance of CSCs and their mitochondria properties remain unclear. Mitochondriatargeted agents are considerably more effective compared to other agents in triggering apoptosis of CSCs, as well as general cancer cells, via mitochondrial dysfunction. Mitochondrial metabolism is altered in cancer cells because of their reliance on glycolytic intermediates, which are normally destined for oxidative phosphorylation. Therefore, inhibiting cancer-specific modifications in mitochondrial metabolism, increasing reactive oxygen species production, or stimulating mitochondrial permeabilization transition could be promising new therapeutic strategies to activate cell death in CSCs as well, as in general cancer cells. This review analyzed mitochondrial function and its potential as a therapeutic target to induce cell death in CSCs. Furthermore, combined treatment with mitochondriatargeted drugs will be a promising strategy for the treatment of relapsed and refractory cancer.

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Human mitochondrial peroxiredoxin 5 protects from mitochondrial DNA damages induced by hydrogen peroxide

Cited by 132 publications

References 41 publications

EstradiolIn VivoRegulation of Brain Mitochondrial Proteome

EstradiolIn VivoRegulation of Brain Mitochondrial Proteome

Evidence of Oxidative Stress in the Pathogenesis of Fuchs Endothelial Corneal Dystrophy

Mitochondria as therapeutic targets for cancer stem cells

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