Superoxide dismutase model studies

Ceballos-Picot, I., Nicole, A., and 8inet, P. M., 1992, Cellular clones and transgenic mice overexpressing copper-zinc superoxide dismutase Models for the study of free radical metabolism and aging, in Free Radicals and Aging (I. Emerit and B. chance, eds.), pp. 89-98, Birkhauser, Basel, 8witzer-land. 

Nickel is found in thiolate/sulflde environment in the [NiFe]-hydrogenases and in CODH/ACS.33 In addition, either a mononuclear Ni-thiolate site or a dinuclear cysteine-S bridged structure are assumed plausible for the new class of Ni-containing superoxide dismutases, NiSOD (A).34 [NiFe]-hydrogenase catalyzes the two-electron redox chemistry of dihydrogen. Several crystal structures of [NiFe]-hydrogenases have demonstrated that the active site of the enzyme consists of a heterodinuclear Ni—Fe unit bound to thiolate sulfurs of cysteine residues with a Ni—Fe distance below 3 A (4) 35-39 This heterodinuclear active site has been the target of extensive model studies, which are summarized in Section 6.3.4.12.5. 

The mitochondrial dysfunctionality seen in manganese neurotoxicity might be related to the accumulation of reactive oxygen species (Verity, 1999). Mitochondrial Mn superoxide dismutase (MnSOD) is found to be low or absent in tumour cells and may act as a tumour suppressor. It is induced by inflammatory cytokines like TNF, presumably to protect host cells. In a rat model, iron-rich diets were found to decrease MnSOD activity, although a recent study reported that in rat epithelial cell cultures iron supplementation increased MnSOD protein levels and activity, but did not compromise the ability of inflammatory mediators like TNF to further increase the enzyme activity (Kuratko, 1999). 

In animal models, milk thistle purportedly limits hepatic injury associated with a variety of toxins, including Amanita mushrooms, galactosamine, carbon tetrachloride, acetaminophen, radiation, cold ischemia, and ethanol. In vitro studies and some in vivo studies demonstrate that silymarin reduces lipid peroxidation, scavenges free radicals, and enhances glutathione and superoxide dismutase levels. This may contribute to membrane stabilization and reduce toxin entry. 

Hydrogen peroxide Model studies on catalases, peroxidases, and superoxide dismutases have provided insights into biological protection against oxidative damage. 

The first application on a biological system was performed in the mid-90 s on a gas phase cluster model of the active site of superoxide dismutase [11]. Since then a rapidly increasing number of applications to biological systems have been reported. In this article, we are trying to give an overview of the current status by giving a short outline of the studies that appeared so far in the literature and by presenting selected examples from our own work on enzymatic systems. 

This is a widely studied cell line derived from a human cervix adenocarcinoma (Gey et al, 1952). The cells are epithelial-like in morphology and are susceptible to polio virus type 1 and adenovirus type 3. HeLa cells are used for the expression of recombinant proteins, including mouse metallothionein 1 gene, human Cu/Zn superoxide dismutase and hepatitis B surface antigen. They have been widely used as an in vitro model system because of the ease with which they can be cultivated but one drawback of this is that the cell line has been responsible for widespread contamination of other cell lines (Nelson-Rees et al, 1981). 

Large biological molecules, such as superoxide dismutase (SOD), triose phosphate isomerase (TIM), acetylcholinesterase, rhinovirus, bacteriorhodop-sin, antibodies, RNA, and DNA, have become accessible to theoretical study recently as a result of the availability of modern computers and sophisticated theories.Two rapidly emerging areas of interest are the computation of electrostatic interactions using continuum models- - and the simulation of diffusional motion in biopolymers and the diffusional encounters between lig-... 

Pharmacology In vitro studies show that milk thistle reduces lipid peroxidation, scavenges free radicals, enhances superoxide dismutase, inhibits formation of leukotrienes, and increases hepatocyte RNA polymerase activity. In animal models, milk thistle protects against liver injury caused by alcohol, acetaminophen, and amanita mushrooms. The outcomes of clinical trials in patients with liver disease caused by alcohol have been mixed. In viral hepatitis and liver injury caused by amanita mushrooms, results of clinical trials have been mainly favorable. A commercial preparation of silybin (an isomer of silymarin) is available in some countries as an antidote to Amanita phalloides mushroom poisoning. 

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