Free radical scavenging actions of metallothionein isoforms I and II

Kumari, Monika; Hiramatsu, Midori; Ebadi, Manuchair

doi:10.1080/10715769800300111

Cited by 220 publications

(136 citation statements)

References 55 publications

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“…Since MT isomers help protect cells from oxidative stress due to excess metal ions, such as cadmium, zinc, and copper, [55][56][57][58] Table S8). …”

Section: Contribution Of Cu Ionsmentioning

confidence: 99%

Molecular Responses of Human Lung Epithelial Cells to the Toxicity of Copper Oxide Nanoparticles Inferred from Whole Genome Expression Analysis

et al. 2011

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This study proposes a molecular mechanism for lung epithelial A549 cells response to copper oxide nanoparticles (CuO-NPs) related to Cu ions released from CuO-NPs. Cells that survived exposure to CuO-NPs arrested the cell cycle as a result of the downregulation of proliferating cell nuclear antigen (PCNA), cell division control 2 (CDC2), cyclin B1 (CCNB1), target protein for Xklp2 (TPX2), aurora kinase A (AURKA) and B (AURKB). Furthermore, cell death was avoided through the induced expression of nuclear receptors NR4A1 and NR4A3, and growth arrest and DNA damage-inducible 45 β and γ (GADD45B and GADD45G, respectively). The downregulation of CDC2, CCNB1, TPX2, AURKA, and AURKB, the expressions of which are involved in cell cycle arrest, was attributed to Cu ions released from CuO-NPs into medium. NR4A1 and NR4A3 expression was also induced by Cu ions released into medium. The expression of GADD45B and GADD45G activated the p38 pathway that was involved in escape from cell death. The upregulation of GADD45B and GADD45G was not observed with Cu ions released into medium but was observed in cells exposed to CuO-NPs. However, because the expression of the genes was also

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“…Since MT isomers help protect cells from oxidative stress due to excess metal ions, such as cadmium, zinc, and copper, [55][56][57][58] Table S8). …”

Section: Contribution Of Cu Ionsmentioning

confidence: 99%

Molecular Responses of Human Lung Epithelial Cells to the Toxicity of Copper Oxide Nanoparticles Inferred from Whole Genome Expression Analysis

et al. 2011

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“…MT protects against many agents known to act through ROS, including hydrogen peroxide, radiation, glutathione depletors, adriamycin, and xanthine oxidase (11,12). MT is distinct among ROS scavengers in the breadth of its protection, in that it scavenges nitric oxide radicals (13), superoxide radicals (14), and hydroxyl radicals (15), which are the most destructive ROS species (11). MT scavenging of hydroxyl radicals is especially potent; the rate constant of MT for reaction with hydroxyl radical (11) is Ͼ100-fold higher than that of glutathione (16), and MT is 50 times more effective than glutathione in protecting DNA from hydroxyl radicals on a molar basis (17).…”

mentioning

confidence: 99%

Overexpression of Metallothionein in Pancreatic β-Cells Reduces Streptozotocin-Induced DNA Damage and Diabetes

et al. 2001

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The release of reactive oxygen species (ROS) has been proposed as a cause of streptozotocin (STZ)-induced ␤-cell damage. This initiates a destructive cascade, consisting of DNA damage, excess activation of the DNA repair enzyme poly(ADP-ribose) polymerase, and depletion of cellular NAD ؉ . Metallothionein (MT) is an inducible antioxidant protein that has been shown to protect DNA from chemical damage in several cell types. Therefore, we examined whether overexpression of MT could protect ␤-cell DNA and thereby prevent STZinduced diabetes. Two lines of transgenic mice were produced with up to a 30-fold elevation in ␤-cell MT. Cultured islets from control mice and MT transgenic mice were exposed to STZ. MT was found to decrease STZ-induced islet disruption, DNA breakage, and depletion of NAD ؉ . To assess in vivo protection, transgenic and control mice were injected with STZ. Transgenic mice had significantly reduced hyperglycemia. Ultrastructural examination of islets from STZ-treated mice showed that MT prevented degranulation and cell death. These results demonstrate that MT can reduce diabetes and confirm the DNA damage mechanism of STZ-induced ␤-cell death. Diabetes 50:2040 -2046, 2001 P ancreatic ␤-cells (1) are extremely vulnerable to damage caused by reactive oxygen species (ROS). A striking example of ␤-cell vulnerability is the severe damage done by streptozotocin (STZ). This natural toxin has several destructive actions, including DNA methylation (2), protein modification (3), and ROS generation (4). STZ enters the cytoplasm via GLUT2, which is the ␤-cell's glucose transporter (5). The presence of this transporter may account for part of the specific vulnerability of the ␤-cell. However, GLUT2 is also present in the liver and kidney, tissues that are relatively resistant to STZ damage. The much greater sensitivity of the ␤-cell is probably due to its very low level of antioxidant enzyme expression and activity (6 -8), which leaves it unable to inactivate ROS. It has been demonstrated in vivo that overexpression of the antiapoptotic, antioxidant protein thioredoxin (9), as well as the antioxidant protein catalase (10), protects the ␤-cell from STZ. However, it is not possible to markedly induce these proteins in vivo. Therefore, we are exploring the potential of another antioxidant protein that is highly inducible, metallothionein (MT).MTs are a family of low-molecular weight cysteine-rich proteins that bind heavy metals with high affinity. MT appears to play important roles in zinc homeostasis and ROS protection. Both functions are due to the presence of abundant cysteine residues. MT protects against many agents known to act through ROS, including hydrogen peroxide, radiation, glutathione depletors, adriamycin, and xanthine oxidase (11,12). MT is distinct among ROS scavengers in the breadth of its protection, in that it scavenges nitric oxide radicals (13), superoxide radicals (14), and hydroxyl radicals (15), which are the most destructive ROS species (11). MT scavenging of hydroxyl radicals is especi...

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“…The transcript with the highest level of regulation (8-fold induction in skeletal muscle) was the gene coding for metallothionein-2. This protein was reported to bind zinc and copper and is considered to have a role in protection against oxidative damage 36 . Further details on the physiological role of metallothionein-2 are not known.…”

Section: Discussionmentioning

confidence: 99%

“…Most notable is the significant 8-fold induction of transcripts coding for metallothionein-2 in muscle, and a smaller 2.7-fold induction was also observed in the heart (Table 1). Metallothionein-2 is a zinc and copper-binding protein that has been suggested to have a role in protection against oxidative damage 36 , but its detailed cellular role is to date unknown. It might be speculated that this gene and possibly some of the other detected genes are induced to deal with reactive oxygen species generated during GFP chromophore formation 37 .…”

Section: Calcium Imaging In Tissue Explantsmentioning

confidence: 99%

Biocompatibility of a genetically encoded calcium indicator in a transgenic mouse model

et al. 2012

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Engineering efforts of genetically encoded calcium indicators predominantly focused on enhancing fluorescence changes, but how indicator expression affects the physiology of host organisms is often overlooked. Here, we demonstrate biocompatibility and widespread functional expression of the genetically encoded calcium indicator Tn-XXL in a transgenic mouse model. To validate the model and characterize potential effects of indicator expression we assessed both indicator function and a variety of host parameters, such as anatomy, physiology, behaviour and gene expression profiles in these mice. We also demonstrate the usefulness of primary cells and organ explants prepared from these mice for imaging applications. Although we find mild signatures of indicator expression that may be further reduced in future sensor generations, the 'green' indicator mice generated provide a well-characterized resource of primary cells and tissues for in vitro and in vivo calcium imaging applications.

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Free radical scavenging actions of metallothionein isoforms I and II

Cited by 220 publications

References 55 publications

Molecular Responses of Human Lung Epithelial Cells to the Toxicity of Copper Oxide Nanoparticles Inferred from Whole Genome Expression Analysis

Molecular Responses of Human Lung Epithelial Cells to the Toxicity of Copper Oxide Nanoparticles Inferred from Whole Genome Expression Analysis

Overexpression of Metallothionein in Pancreatic β-Cells Reduces Streptozotocin-Induced DNA Damage and Diabetes

Biocompatibility of a genetically encoded calcium indicator in a transgenic mouse model

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