The neurotoxin MPTP does not affect striatal superoxide dismutase activity in mice

Intraneuronal superoxide generation may be a possible mechanism of the dopaminergic (DA) neurotoxicity of MPTP. In such case, MPTP might theoretically affect superoxide dismutase (SOD) activity. We determined SOD activity and DA levels in striata of mice at 0.5, 1, 4, 16, 24 h or 7 days after an acute single injection of MPTP (40 mg/kg, s.c.). MPTP produced marked striatal DA depletions from 4 h post-treatment but SOD activity remained unaltered and similar to controls at all time points. Intrastriatal injections of purified SOD 15 min prior to systemic administration of MPTP did not attenuate the MPTP-induced striatal DA depletions in mice at 7 days post-treatment. Combined administration of MPTP with the SOD inhibitor diethyldithiocarbamate markedly enhanced striatal DA decreases produced by MPTP alone. Findings suggest that MPTP does not act via inhibition of SOD. Therefore, potentiation of MPTP toxicity by diethyldithiocarbamate may be due to interference with other enzymatic systems.     

Effect of aging on pulmonary superoxide dismutase

Pulmonary Cu,Zn superoxide dismutase was examined in young (1-month-old), adult (4-5-month-old) and aged (24-months-old) rats to determine if partially inactive forms of the enzyme accumulate in the lung with age. Measurement of Cu,Zn superoxide dismutase activity in lung homogenates showed that total Cu,Zn superoxide dismutase activity/mg DNA was essentially the same in adult and aged rats. The average value of Cu,Zn superoxide dismutase/mg DNA for young rats was less than half that of adult and aged rats. Cu,Zn superoxide dismutase was purified from the lung homogenates and fractionated into isoelectric variants by either isoelectric focusing or chromatofocusing. Three main isoelectric variants of Cu,Zn superoxide dismutase were recovered with pI values of 5.15, 4.88 and 4.75. In all age groups studied, the pI 4.88 variant had a markedly higher specific activity than the other two variants, as well as the highest metal content and greatest resistance to inactivation of all three variants. The pI 4.88 variant declined from 88% of the total Cu,Zn superoxide dismutase activity in the young animals to only 70% in the aged animals. The results of this study indicate that the proportion of the relatively inactive forms of pulmonary Cu,Zn superoxide dismutase increased with age.     

Age-related cochlear hair cell loss is enhanced in mice lacking copper/zinc superoxide dismutase.

Age-related hearing loss in humans and many strains of mice is associated with a base-to-apex gradient of cochlear hair cell loss. To determine if copper/zinc superoxide dismutase (Cu/Zn SOD) deficiency influences age-related cochlear pathology, we compared hair cell losses in cochleas obtained from 2-, 7-, and 17- to 19-month-old wild type (WT) mice with normal levels of Cu/Zn SOD and mutant knockout (KO) mice with a targeted deletion of Sod1, the gene that codes for Cu/Zn SOD. WT and KO mice exhibited similar patterns of hair cell loss with age, i.e., a baso-apical progression of hair cell loss, with greater loss of outer hair cells than inner hair cells. Within each age group, the magnitude of loss was much greater in KO mice compared to WT mice. The results indicate that Cu/Zn SOD deficiency potentiates cochlear hair cell degeneration, presumably through metabolic pathways involving the superoxide radical.     

Hippocampal memory and plasticity in superoxide dismutase mutant mice

The reactive oxygen species (ROS) superoxide is well known for its role in disease mechanisms. Mounting evidence indicates, however, that superoxide also is generated for useful purposes and contributes to normal physiologic function. Studies with transgenic mice that overexpress superoxide scavengers show that certain types of memory function and underlying neuronal processes are impaired under conditions of severely reduced superoxide signaling. These findings have implications for the use of antioxidant treatments as well as for our understanding of the signaling events involved in cognition.     

Identification of superoxide dismutase activity in Borrelia burgdorferi.

Infective and noninfective strains of Borrelia burgdorferi, along with Borrelia afzelii and Borrelia garinii, possessed a single iron-containing superoxide dismutase (SOD). None of the Lyme disease spirochetes tested possessed catalase or peroxidase activities. The borrelial SOD was not inducible by growth with increased oxygen concentrations and thus appeared to be produced constitutively.     

Role of manganese-containing superoxide dismutase in oxidative stress and virulence of Streptococcus pneumoniae

Streptococcus pneumoniae was shown to contain two types of superoxide dismutase, MnSOD and FeSOD. Levels of MnSOD increased during growth in an aerobic environment. The sodA gene, encoding MnSOD, of virulent S. pneumoniae type 2 strain D39 was inactivated to give mutant D39HY1. Aerobically, D39HY1 had a lower growth rate than the wild type and exhibited susceptibility to the redox-active compound paraquat, but anaerobic growth of D39HY1 was identical to that of the wild type. Virulence studies showed that the median survival time of mice infected intranasally with D39HY1 was significantly longer than that of mice infected with the wild-type pneumococcus. In contrast to the wild type, D39HY1 did not multiply in lungs during the first 24 h but thereafter grew at the same rate as the wild type. Appearance in the bloodstream was also delayed, but growth in the blood was unimpaired by the sodA mutation. The pattern of inflammation in lungs infected with D39HY1 differed from that in wild-type-infected mice. After infection with D39HY1, neutrophils were densely packed around bronchioles, in contrast to the wild-type infection, where neutrophils were more diffusely localized.     

Gene transfer of extracellular superoxide dismutase to atherosclerotic mice

Clinical and epidemiological studies have provided circumstantial evidence that oxidized low-density lipoprotein (LDL) and antioxidants are involved in the pathogenesis of atherosclerosis. Superoxide dismutases (SODs) have been shown in vitro to protect LDL from deleterious effects of superoxide anions. In the present study, we have used adenoviral gene transfer to determine effect of extracellular SOD (EC-SOD) on atherogenesis in LDL receptor -/- mice. Intravenous administration of EC-SOD adenovirus (2 x 10(9) plaque forming units) into tail vein targeted transgene mainly to liver and induced a 3.5- to sevenfold increase in plasma total SOD activity. EC-SOD was secreted into circulation for 2-3 weeks mostly in a truncated B-form, suggesting that endogenous proteolytic mechanisms control the level and distribution of the enzyme. Therapeutic potential was determined by measuring plasma resistance against copper oxidation and analyzing atherosclerotic lesion areas in aortas of LDL receptor -/- mice. Mice were kept on a cholesterol diet for 10 weeks before gene transfer and 3 or 6 weeks after the gene transfer. Results showed a tendency for a reduction in the overall lesion area after EC-SOD gene transfer as compared with LacZ transduced control mice, but the difference did not reach statistical significance. It is concluded that short-term overexpression of EC-SOD in vivo does not affect atherogenesis in LDL receptor -/- mice.     

Superoxide dismutase activity and superoxide dismutase-1 gene methylation in normal and tumoral human breast tissues.

The superoxide dismutase (SOD) activities in normal and tumor breast tissues from 14 human females were determined by the epinephrine autoxidation assay. SOD levels showed a marked interindividual variability in normal and malignant cells. However, each donor had a higher SOD activity in cancer than in normal tissue samples. In three cases in which Mn- and CuZnSOD activities were determined, it was found that tumoral increases in SOD were due to increases in both enzymatic forms. Therefore, it seems reasonable to assume a similar situation for all cases in our series. The level of DNA methylation in the SOD-1 gene was assessed in the first four donors. The four cases exhibited full methylation of SOD-1 genes corresponding to normal as well as to cancer cells. It is concluded that the variability in CuZnSOD activities is not related with the state of methylation of the SOD-1 gene. MspI restriction fragment polymorphisms between DNA samples from normal and malignant cells were detected in the four DNA donors. This phenomenon may be due to point mutations changing the frequency of MspI sites or to methylation of the external C in CCGG sequences.     

S-甲基异硫脲对阿霉素致大鼠心肌组织超氧化物歧化酶、谷胱甘肽过氧化物酶活性改变的影响

目的:探讨S-甲基异硫脲(SMT)对阿霉素(ADM)所致大鼠心肌组织超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GPx)活性改变的影响。 方法:给大鼠腹腔注射ADM(10.0 mg·kg^-1)1次，给ADM处理的大鼠静脉注射不同剂量的SMT(每天1次，共3次)进行干预。用分光光度法测定心肌组织丙二醛(MDA)含量、NO2-/NO3-含量、锰超氧化物歧化酶(MnSOD)活性、铜-锌超氧化物歧化酶（Cu-ZnSOD）活性、谷胱甘肽过氧化物酶(GPx)活性、一氧化氮合酶活性；用酶的速率法测定血清肌酸激酶(CK)的同功酶CK-MB活性；用逆转录-聚合酶链反应方法检测心肌组织MnSOD mRNA、Cu-ZnSOD mRNA、GPx mRNA、诱导型一氧化氮合酶(iNOS)mRNA表达。 结果:SMT(5.0，10.0，20.0 mg· kg^-1)3个干预组心肌组织MDA含量、NO2-/NO3-含量、iNOS活性及血清CK-MB活性明显低于ADM组(P<0.01)，而其心肌组织MnSOD mRNA、Cu-ZnSOD mRNA、GPx mRNA表达水平及其酶活性明显高于ADM组(P<0.01)。 结论:SMT拮抗ADM抑制心肌组织MnSOD mRNA、Cu-ZnSOD mRNA、GPx mRNA表达而拮抗ADM抑制这些酶的活性。     

Effect of prenatal lead exposure on superoxide dismutase activity in the brain and liver of rat fetuses

Prenatal lead exposure had a damaging effect on Cu/Zn superoxide dismutase activity in the brain and liver of rat fetuses (20 days of gestation). The decrease in Cu/Zn superoxide dismutase activity in the brain and liver of treated fetuses reflects activation of free radical processes and impairment of the antioxidant defense system during prenatal lead exposure. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 144, No. 12, pp. 632–634, December, 2007     

米诺环素局部用药对牙周炎患者龈沟液中超氧化物歧化酶活性的影响

目的： 比较应用米诺环素软膏治疗前后牙周炎患者临床指标及龈沟液中超氧化物歧化酶(SOD)活性的变化。方法：成人牙周炎患者30例，分成2组，实验组常规牙周治疗+米诺环素软膏，对照组仅给予常规牙周治疗，记录两组治疗前后牙龈指数（GI）、牙周探诊深度（PD）、附着丧失(AL)； 并用放射免疫法检测两组龈沟液SOD活性。结果：（1）治疗后，试验组牙龈指数（GI）、牙周探诊深度（PD）均明显低于对照组（P<0.05，P<0.01）；而治疗前两组比较，上述指标未见显著差别。 （2）治疗前，实验组龈沟液SOD活性与对照组比较无显著差别（P>0.05），而治疗后，实验组龈沟液SOD活性显著高于对照组 (P<0.05)。结论：米诺环素局部用药可显著降低牙周炎患者牙龈指数（GI）、牙周探诊深度（PD）并提高龈沟液SOD活性。     

米诺环素局部用药对牙周炎患者龈沟液中超氧化物歧化酶(SOD)活性的影响

目的比较应用米诺环素软膏治疗前后牙周炎患者临床指标及龈沟液中超氧化物歧化酶(SOD)活性的变化.方法成人牙周炎患者30例,分成2组,实验组常规牙周治疗+米诺环素软膏,对照组仅给予常规牙周治疗,记录两组治疗前后牙龈指数(GI)、牙周探诊深度(PD)、附着丧失(AL);并用放射免疫法检测两组龈沟液SOD活性.结果(1)治疗后,试验组牙龈指数(GI)、牙周探诊深度(PD)均明显低于对照组(P＜0.05,P＜0.01);而治疗前两组比较,上述指标未见显著差别.(2)治疗前,实验组龈沟液SOD活性与对照组比较无显著差别(P＞0.05),而治疗后,实验组龈沟液SOD活性显著高于对照组(P＜0.05).结论米诺环素局部用药可显著降低牙周炎患者牙龈指数(GI)、牙周探诊深度(PD)并提高龈沟液SOD活性.     

Extracellular superoxide dismutase overexpression protects against aging-induced cognitive impairment in mice

Extracellular superoxide dismutase (EC-SOD) controls the availability of extracellular superoxide and appears to play a role in controlling oxidative stress and intercellular signaling. Whether EC-SOD overexpression would help or hinder neurobehavioral function appears to depend on the age of the individual. In young adult mice, we have found that EC-SOD overexpression can interfere with learning on the radial-arm maze, possibly by reducing control over nitric oxide neurotransmission. In aged mice, we found, in the current study, that EC-SOD overexpression greatly improves learning on the radial-arm maze. Control (N = 17) and EC-SOD overexpressing mice (N = 13) acquired the 8-arm radial maze over 21 sessions of training. The EC-SOD overexpressing mice had significantly better choice accuracy than the control mice (p < 0.005). The EC-SOD overexpressing mice averaged 6.34 ± 0.22 correct arm entries before an error (entries to repeat) during the acquisition phase, while the control mice averaged 5.18 ± 0.22 entries to repeat. EC-SOD genotype did not cause a main effect on response latency. The advantage held by the EC-SOD overexpressing mice persisted during the eight-session post-acquisition phase of testing (p < 0.01). When there was a shift from high to low levels of motivation by reducing the period of food restriction before testing, the EC-SOD overexpression-induced improvement was reduced slightly, but it was still significant compared with the wild-type controls (p < 0.025). Then, after 4 months of no testing, the mice were tested for retention and reacquisition of performance on the radial-arm maze. The EC-SOD overexpressing mice maintained their significantly better choice accuracy (p < 0.05). Enhancement of EC-SOD activity appears to improve learning and memory performance, specifically in aging mice. EC-SOD mimetic treatment during the course of aging may hold promise for aging-induced cognitive impairment.     

Quantitative determination of activity of multiple forms of superoxide dismutase

A quantitative method of determination of the activity of multiple forms of superoxide dismutase (SOD), based on separation of the forms of the enzyme of gel electrophoresis, elution from the gel, and determination of inhibition of the reduction of nitro-BT in a system of NADH and phenazine metasulfate, is described. Partially purified bovine erythrocyte SOD was shown to separate into three forms; the activity of form 2 is much lower than the degree of its staining for protein.Institute of Clinical and Experimental Medicine, Academy of Medical Sciences of the USSR, Siberian Branch, Novosibirsk (Presented by Academician of the Academy of Medical Sciences of the USSR V. P. Kaznacheev.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 6, pp. 762–764, June, 1977.     

Effect of superoxide dismutase on convulsive seizures in rat models of epilepsy

Intravenous injections of superoxide dismutase into rats with amygdaline kindling mitigated spontaneous and electrostimulation-induced epileptic seizures and raised the thresholds of electric current for their elicitation; these seizures of reduced intensity were observed during 3 days following chronic (for 6 days) treatment with this enzyme. In contrast, superoxide dismutase injections had no effect on the convulsions induced by electric shock or corazole. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 7, pp. 20–22, July, 1995 Presented by A. N. Klimov, Member of the Russian Academy of Medical Sciences     

Genetic modifiers of the phenotype of mice deficient in mitochondrial superoxide dismutase

Sod2-/- mice, which are deficient in the mitochondrial form of superoxide dismutase (MnSOD), have a short survival time that is strongly affected by genetic background. This suggests the existence of genetic modifiers that are capable of modulating the degree of mitochondrial oxidative damage caused by the MnSOD deficiency, thereby altering longevity. To identify these modifier(s), we generated recombinant congenic mice with quantitative trait loci (QTL) containing the putative genetic modifiers on the short-lived C57BL/6J genetic background. MnSOD deficient C57BL/6J mice with a QTL from the distal region of chromosome 13 from DBA/2J were able to survive for as long as those generated on the long-lived DBA/2J background. Within this region, the gene encoding nicotinamide nucleotide transhydrogenase (Nnt) was found to be defective in C57BL/6J mice, and no mature NNT protein could be detected. The forward reaction of NNT, a nuclear-encoded mitochondrial inner membrane protein, couples the generation of NADPH to proton transport and provides NADPH for the regeneration of two important antioxidant compounds, glutathione and thioredoxin, in the mitochondria. This action of NNT could explain its putative protective role in MnSOD-deficient mice.