Peroxiredoxin I is overexpressed in oncocytic lesions of salivary glands

Demasi, Ana Paula Dias; Furuse, Cristiane; Altemani, Albina; Junqueira, José Luiz Cintra; Oliveira, Paulo Roberto Grimaldi; Araújo, Vera Cavalcanti de

doi:10.1111/j.1600-0714.2009.00753.x

Cited by 16 publications

(8 citation statements)

References 34 publications

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“…Therefore, upregulated expression of TPx enzyme seems to coincide with the resistant response of cells against radiation-induced ROS and cell death. Higher expression of certain isoforms of TPx as observed in several cancers [37], [38], [39], [40], [41], [42] has been shown to inhibit stress-induced increase in intracellular H 2 O 2 [43] and is also associated with resistance to radiation [24] or chemical stress [44]. Present findings in these model radioresistant cells further support the putative role of TPx in cellular radioresistance.…”

Section: Discussionsupporting

confidence: 79%

Evidence for Involvement of Cytosolic Thioredoxin Peroxidase in the Excessive Resistance of Sf9 Lepidopteran Insect Cells against Radiation-Induced Apoptosis

2013

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Lepidopteran insect cells display 50–100 times higher radioresistance compared to human cells, and reportedly have more efficient antioxidant system that can significantly reduce radiation-induced oxidative stress and cell death. However, the antioxidant mechanisms that contribute substantially to this excessive resistance still need to be understood thoroughly. In this study, we investigated the role of thioredoxin peroxidase (TPx) in high-dose γ-radiation response of Sf9 cell line derived from Spodoptera frugiperda, the Fall armyworm. We identified a TPx orthologue (Sf-TPx) in Spodoptera system, with primarily cytosolic localization. Gamma-irradiation at 500 Gy dose significantly up-regulated Sf-TPx, while higher doses (1000 Gy–2000 Gy) had no such effect. G2/M checkpoint induced following 500 Gy was associated with transition of Sf-TPx decamer into enzymatically active dimer. Same effect was observed during G2/M block induced by 5 nM okadaic acid or 10 µM CDK1 (cycline dependent kinase-1) inhibitor roscovitine, thus indicating that radiation-induced Sf-TPx activity is mediated by CDKs. Accumulation of TPx dimer form during G2/M checkpoint might favour higher peroxidase activity facilitating efficient survival at this dose. Confirming this, higher lethal doses (1000 Gy–2000 Gy) caused significantly less accumulation of dimer form and induced dose-dependent apoptosis. A ∼50% knock-down of Sf-TPx by siRNA caused remarkable increase in radiation-induced ROS as well as caspase-3 dependent radiation-induced apoptosis, clearly implying TPx role in the radioresistance of Sf9 cells. Quite importantly, our study demonstrates for the first time that thioredoxin peroxidase contributes significantly in the radioresistance of Lepidopteran Sf9 insect cells, especially in their exemplary resistance against radiation-induced apoptosis. This is an important insight into the antioxidant mechanisms existing in this highly stress-resistant model cell system.

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Section: Discussionsupporting

confidence: 79%

Evidence for Involvement of Cytosolic Thioredoxin Peroxidase in the Excessive Resistance of Sf9 Lepidopteran Insect Cells against Radiation-Induced Apoptosis

2013

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“…PRX1 and PRX2 are known to be elevated in several human cancer cells and tissues such as in mesothelioma [31], breast [32], and head-and-neck cancers [33]. Elevated PRX1 has also been implicated in lung cancer tissues [23].…”

Section: Discussionmentioning

confidence: 99%

Peroxiredoxins and tropomyosins as plasma biomarkers for lung cancer and asbestos exposure

et al. 2012

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“…In support of our hypothesis, ROS levels in thyroid oncocytoma derived XTC.UC1 cells showed no alterations. This was explained by the differential expression of ROS detoxifying enzymes [ 15 , 57 ]. In this regard, the gamma-glutamyltranspeptidase 1 and 5 (GGT1, GGT5), and the betaine homocysteine S-methyltransferase (BHMT), contributing to intracellular GSH and homocysteine maintenance were significantly down-regulated in renal oncocytomas, indicating a degradation brake in the gamma-glutamyl cycle, which might be the molecular reason for the high GSH levels.…”

Section: Discussionmentioning

confidence: 99%

Renal oncocytoma characterized by the defective complex I of the respiratory chain boosts the synthesis of the ROS scavenger glutathione

et al. 2017

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Renal oncocytomas are rare benign tumors of the kidney and characterized by a deficient complex I (CI) enzyme activity of the oxidative phosphorylation (OXPHOS) system caused by mitochondrial DNA (mtDNA) mutations. Yet, little is known about the underlying molecular mechanisms and alterations of metabolic pathways in this tumor. We compared renal oncocytomas with adjacent matched normal kidney tissues on a global scale by multi-omics approaches, including whole exome sequencing (WES), proteomics, metabolomics, and metabolic pathway simulation. The abundance of proteins localized to mitochondria increased more than 2-fold, the only exception was a strong decrease in the abundance for CI subunits that revealed several pathogenic heteroplasmic mtDNA mutations by WES. We also observed renal oncocytomas to dysregulate main metabolic pathways, shunting away from gluconeogenesis and lipid metabolism. Nevertheless, the abundance of energy carrier molecules such as NAD+, NADH, NADP, ATP, and ADP were significantly higher in renal oncocytomas. Finally, a substantial 5000-fold increase of the reactive oxygen species scavenger glutathione can be regarded as a new hallmark of renal oncocytoma. Our findings demonstrate that renal oncocytomas undergo a metabolic switch to eliminate ATP consuming processes to ensure a sufficient energy supply for the tumor.

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Peroxiredoxin I is overexpressed in oncocytic lesions of salivary glands

Cited by 16 publications

References 34 publications

Evidence for Involvement of Cytosolic Thioredoxin Peroxidase in the Excessive Resistance of Sf9 Lepidopteran Insect Cells against Radiation-Induced Apoptosis

Evidence for Involvement of Cytosolic Thioredoxin Peroxidase in the Excessive Resistance of Sf9 Lepidopteran Insect Cells against Radiation-Induced Apoptosis

Peroxiredoxins and tropomyosins as plasma biomarkers for lung cancer and asbestos exposure

Renal oncocytoma characterized by the defective complex I of the respiratory chain boosts the synthesis of the ROS scavenger glutathione

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