Metallothionein Inhibits Peroxynitrite-induced DNA and Lipoprotein Damage

Abstract

Previous studies have demonstrated that metallothionein functions as an antioxidant that protects against oxidative DNA, protein, and lipid damage induced by superoxide anion, hydrogen peroxide, hydroxyl radical, and nitric oxide. The present study was undertaken to test the hypothesis that metallothionein also protects from DNA and lipoprotein damage induced by peroxynitrite, an important reactive nitrogen species that causes a diversity of pathological processes. A cell-free system was used. DNA damage was detected by the mobility of plasmid DNA in electrophoresis. Oxidation of low density lipoprotein was measured by a thiobarbituric acidreactive substance, which was confirmed by lipid hydroperoxide assay. Plasmid DNA damage and low density lipoprotein oxidation were induced by 3-morpholinosydnomine, which produces peroxynitrite through the reaction between nitric oxide and superoxide anion or by synthesized peroxynitrite directly. DNA damage by 3-morpholinosydnomine was prevented by both metallothionein and superoxide dismutase, whereas the damage caused by peroxynitrite was prevented by metallothionein only. The oxidation of low density lipoprotein by 3-morpholinosydnomine and peroxynitrite was also significantly inhibited by metallothionein. This study thus demonstrates that metallothionein may react directly with peroxynitrite to prevent DNA and lipoprotein damage induced by this pathological reactive nitrogen species.

Oxidative and nitrosative stress in acute renal ischemia

“…Recently, DNA damage was induced in A549 epithelial cells by crocidolite, the most carcinogenic form of asbestos, with the induction of NO and was detected as 8-OHdG formation, which was significantly inhibited by 1 mM aminoguanidine (11). In addition, peroxynitrite-induced DNA damage and lipoprotein modification were recently reported in a cellfree system (10). In the present study, 8-OHdG was used as a marker of DNA damage.…”

The Late and Persistent Pathogenic Effects of Cadmium at Very Low Levels on the Kidney of Rats

“…For instance, Bauer et al (1980) have reported that Cd 111 was able to occupy the site of Zn in the CuZn-SOD molecule creating an inactive form of the enzyme (CuCd 111 SOD). MT is a cysteine-rich low molecular weight protein, which can bind excess heavy metal ions preventing their toxic effects, and also sequesters several ROSs and RNSs to play an important role in protecting against oxidative stress (Cai et al 1999;Cai et al 2000;Cherian et al 2003;Sato and Bremner 1993). Cd is readily able to induce MT expression in the liver and kidney (Cherian et al 2003).…”

Metallothionein as an Adaptive Protein Prevents Diabetes and its Toxicity

“…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).…”