Antioxidant activity of metallothionein compared with reduced glutathione

Miura, Toshiaki; Muraoka, Sanae; Ogiso, Taketo

doi:10.1016/s0024-3205(97)00156-2

Cited by 109 publications

(65 citation statements)

References 31 publications

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“…Metallothionein are potent´OH scavengers in vitro [14, 20±22] and 38.5-fold to 50-fold more effective in protecting DNA from´OH attacks than glutathione [23,24]. There are four isoforms of MT [25].…”

Section: +mentioning

confidence: 99%

Zinc sulphate induces metallothionein in pancreatic islets of mice and protects against diabetes induced by multiple low doses of streptozotocin

et al. 2000

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Section: +mentioning

confidence: 99%

Zinc sulphate induces metallothionein in pancreatic islets of mice and protects against diabetes induced by multiple low doses of streptozotocin

et al. 2000

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“…Functionally, MT mainly acts as a regulator of metal homeostasi in tissues, especially trace element metals, and also acts as a potent antioxidant to protect cells or tissues from oxidative damage (Klaassen and Liu, 1998;Cai et al, 1999;Kang, 1999). Compared with other antioxidants that can protect specifically against certain damage-SOD against superoxide radical, catalase against hydrogen peroxide, and glutathione peroxidase against hydrogen peroxide and lipid peroxides-MT is a potent antioxidant against a wide range of free radicals including the most active radicals: hydroxyl radical and peroxynitrite (Thornalley and Vasak, 1985;Miura et al, 1997;Cai et al, 1999Cai et al, , 2000aCai and Cherian, 2003).…”

Section: Introductionmentioning

confidence: 99%

Metallothionein as an Adaptive Protein Prevents Diabetes and its Toxicity

Cai

2004

Nonlinearity in Biology, Toxicology, Medicine

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“…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). Probably due to its antioxidant activity, MT can protect DNA against the damage produced by anticancer agents (18) and hydrogen peroxide (19).…”

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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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Antioxidant activity of metallothionein compared with reduced glutathione

Cited by 109 publications

References 31 publications

Zinc sulphate induces metallothionein in pancreatic islets of mice and protects against diabetes induced by multiple low doses of streptozotocin

Zinc sulphate induces metallothionein in pancreatic islets of mice and protects against diabetes induced by multiple low doses of streptozotocin

Metallothionein as an Adaptive Protein Prevents Diabetes and its Toxicity

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

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