Superoxide dismutase inhibition

Roginsky V and Barsukova, T. 2001. Superoxide dismutase inhibits lipid peroxidation in micelles. Chem Phys Lipids 111 (l) 87-91. 

Lipemic activity. Cigarette smoke extract, in macrophages with LDL culture at a dose of 100 Xg/mL, stimulated cholesteryl oleate synthesis approximately equal to 12.5-fold. Enhancement in cholesteryl ester synthesis was dependent on the concentration of smoke-modified LDL and exhibited saturation kinetics. There was extensive fragmentation of apo B. This LDL modification depended on the incubation time and concentration of the smoke extract. Superoxide dismutase inhibited LDL modification by 52%, suggesting that superoxide anion is involved. The results indicated that smoke extract alters LDL into a form recognized and incorporated by macrophages . En-... 

Thiols can also be converted to disulfides, as in the CdS-photocatalyzed conversion of cysteine to cystine In the latter reaction, the uptake of oxygen was pH dependent. Since the reaction rate was not increased in deuterium oxide and was not decreased by added azide, the authors conclude that singlet oxygen is not involved. Since superoxide dismutase inhibited the conversion, a photoinduced electron transfer is probably responsible for the observed transformations. Such organosulfide oxidations may be environmentally important since naturally occurring hematite suffers a photoassisted dissolution in the presence of thiols... 

KMB. In both cases superoxide dismutase inhibited formation of ethylene but catalase did not. Nor did HjOi stimulate the formation of ethylene in the suspensions of granules leading the authors to propose that H2O2 was not an obligatory precursor of the oxidant. In other studies of PMNs stimulated with opsonized zymosan catalase did inhibit formation of ethylene as did superoxide dis-... 

The antibody-dependent lysis of tumor cells by PMNs exhibited some of the characteristics of damage mediated by products of the burst in the presence of tumor cells there was increased consumption of O2, increased formation of O and activation of the hexose monosphosphate shunt However, although a reduction in the concentration of O2 in the medium inhibited lysis neither catalase nor superoxide dismutase inhibited. The lack of effect on these enzymes was attributed to their inability to interpose themselves between the plasma membranes of the PMN and its target. Similar conclusions were reached by Clark, and Klebanoff whose data incriminated the products of the burst by the reduced killing of tumor cells by PMNs from patients with chronic granulomatous disease. Myeloperoxidase, however, appeared not to he required since neither azide or cyanide inhibited and killing by PMNs from patients with inherited deficiency of myeloperoxidase was normal. 

Forman and Fridovich (1973) using an indirect assay whereby O2 was generated either by the action of xanthine oxidase on xanthine or by the mechanical infusion of potassium superoxide in tetrahydrofuran. The generated OJ was allowed to react with ferricytochrome c or with tetra-nitromethane and the product formation was monitored spectroscopically. Details of the two assays are given in Section 11.3. Addition of superoxide dismutase inhibits the formation of products. A rate constant of 2 X 10 M sec was determined for all three enzymes. This value agreed with the rate constant determined by pulse radiolysis for the copper/zinc enzyme (Klug-Roth et al., 1973 Fielden et al., 1974). The mechanism of action of the superoxide dismutases has been investigated by the technique of pulse radiolysis which is described in Section II.2. The bovine erythrocyte copper/zinc enzyme is the most studied form as far as the molecular and catalytic properties are concerned (Rotilio and Fielden,... 

The indirect methods of assaying for superoxide dismutase are the most widely used routine assays because the reagents used are inexpensive, widely available, and usually very sensitive to detection. However, these types of assay are quite susceptible to interferences. Some of these interferences are unfortunately ignored, with the consequence that various discrepancies arise in the results obtained from the various laboratories. These assays can operate at a very low steady-state level of O2 and are considered to be indirect negative assays when superoxide dismutase inhibits the formation of products and indirect positive assays when the enzyme accelerates the formation of products. In the indirect assays a unit of enzyme activity is generally defined as the amount of the enzyme that inhibits the reaction by 50%. 

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. 

Gutteridge and Bannister [335] found that manganese-superoxide dismutase inhibits the degradation of deoxyribose while Qato and Maines [336] reported that drug metabolism activities in the brain are regulated by Mn(ll). Later, Mn(II) was found to induce selective vulnerability in glutathione metabolism and cellular defence meehanisms in rat striatum [337]. 

Superoxide dismutase Inhibition of cell proliferation Inhibition of inflammation Induction of cell-cycle arrest Induction of apoptosis Inhibition of signal transduction pathways Antiangiogenesis... 

In anaesthetised new-born pigs (1 to 5 days old) of either sex, injury of moderate severity (1.9 to 2.1 atm) induced by the lateral fluid percussion brain injury technique phorbol 12,13-dibutyrate (1 imol/l) increased superoxide dismutase-inhibitable nitroblue tetrazoHum reduction from 1 1 to 37 5 pmol/mm (Armstead 1999). 

Neuronal loss was initiated by inhibition of the antioxidant enzyme, superoxide dismntase (EC 1.15.1.1.) type 1, using the copper chelator diethyl-dithiocarbamate (Moskowitz et al. 2001). Continuous diethyldithiocarbamate treatment of Sprague-Dawley rat or C57/B16 mouse hippocampal slice cultures induced delayed neuronal loss beginning at 9 days of treatment that lasted for over 4 weeks. Neuronal loss was significantly attenuated in slice cultures that overexpress superoxide dismutase type 1, suggesting that superoxide dismutase inhibition was responsible. Inhibitors of nitric oxide synthase also attenuated diethyldithiocarbamate-induced neuronal loss. 

Brach MA, Hass R, Sherman ML et al. (1991) Ionizing radiation induces expression and binding activity of the nuclear factor kappa B. J Clin Invest 88 691-695 Breuer R, Tochner Z, Conner MW etal. (1992) Superoxide dismutase inhibits radiation-induced lung injury in hamsters. Lung 170 19-29... 

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