-
Experimental Neurology Mar 1998The overall peroxidation activity in brain tissue by region from patients with Alzheimer's disease (AD) and age-matched controls was determined employing the...
The overall peroxidation activity in brain tissue by region from patients with Alzheimer's disease (AD) and age-matched controls was determined employing the thiobarbituric acid-reactive substances (TBARS) assay, a measure of lipid peroxidation, followed by a determination the activities of the antioxidant enzymes Cu/Zn superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT), in the frontal, temporal, and cerebellar cortex of 10 AD and 9 control brains. The level of TBARS was elevated in all regions, with particular statistical significance in the temporal cortex when compared to age-matched controls. SOD activity was significantly decreased in AD frontal and AD temporal cortex, while catalase activity was significantly decreased in AD temporal cortex. There was no significant difference in GSH-Px activity found in any of the regions examined. This study supports the theory that in AD the brain is affected by increased oxidative stress which, when combined with a decrease in SOD activity, produces oxidative alterations, seen most significantly in temporal cortex in AD, where the pathophysiologic changes are most severe.
Topics: Acatalasia; Aged; Alzheimer Disease; Antioxidants; Brain Chemistry; Cerebellum; Frontal Lobe; Glutathione Peroxidase; Humans; Lipid Peroxidation; Nerve Tissue Proteins; Oxidative Stress; Superoxide Dismutase; Temporal Lobe; Thiobarbituric Acid Reactive Substances
PubMed: 9514828
DOI: 10.1006/exnr.1997.6750 -
Genetics Jul 1989Activated oxygen species have been demonstrated to be the important agents in oxygen toxicity by disrupting the structural and functional integrity of cells through...
Activated oxygen species have been demonstrated to be the important agents in oxygen toxicity by disrupting the structural and functional integrity of cells through lipid peroxidation events, DNA damage and protein inactivation. The biological consequences of free radical damage have long been hypothesized to be a causal agent in many aging-related diseases. Catalase (H2O2:H2O2 oxidoreductase; EC 1.15.1.1) is one of several enzymes involved in the scavenging of oxygen free radicals and free radical derivatives. The structural gene for catalase in Drosophila melanogaster has been localized to region 75D1-76A on chromosome 3L by dosage responses to segmental aneuploidy. This study reports the isolation of a stable deficiency, Df(3L)CatDH104(75C1-2;75F1), that uncovers the catalase locus and the subsequent isolation of six acatalasemic mutants. All catalase mutants are viable under standard culture conditions and recessive lethal mutations within the 75Cl-F1 interval have been shown not to affect catalase activity. Two catalase mutations are amorphic while four are hypomorphic alleles of the Cat+ locus. The lack of intergenic complementation between the six catalase mutations strongly suggests that there is only one functional gene in Drosophila. One acatalesemic mutation was mapped to position 3-47.0 which resides within the catalase dosage sensitive region. While complete loss of catalase activity confers a severe viability effect, residual levels are sufficient to restore viability to wild type levels. These results suggest a threshold effect for viability and offer an explanation for the general lack of phenotypic effects associated with the known mammalian acatalasemics.
Topics: Acatalasia; Alleles; Animals; Catalase; Chromosome Mapping; Drosophila melanogaster; Free Radicals; Hydrogen Peroxide; Mutation; Oxygen; Recombination, Genetic
PubMed: 2503418
DOI: 10.1093/genetics/122.3.643 -
The Tohoku Journal of Experimental... May 1975The kinetics of catalase synthesis and degradation were determined in acatalasemia and normal mouse livers during recovery of catalase activity after inhibition with...
The kinetics of catalase synthesis and degradation were determined in acatalasemia and normal mouse livers during recovery of catalase activity after inhibition with aminotriazole. Catalase turned over with a half life of 10.0 hr in acatalasemia mice and of 19.2 hr in normal mice. The rate of catalase synthesis (Ks) was 0.168 (PU/mg protein/hr) in acatalasemia mice and 0.271 in normal mice. The rate of catalase degradation (KD) was 0.069 and 0.036 per hour in acatalasemia and normal mice, respectively.
Topics: Animals; Catalase; Half-Life; Kinetics; Liver; Mathematics; Mice; Triazoles
PubMed: 1154374
DOI: 10.1620/tjem.116.39 -
Environmental Health and Preventive... May 2003Catalase-deficient mouse strains was initially established by Feinstein et al. through a large scale screening of the progeny of irradiated C3H mice in 1966. Later,...
Catalase-deficient mouse strains was initially established by Feinstein et al. through a large scale screening of the progeny of irradiated C3H mice in 1966. Later, Feinstein provided the mice of catalase mutant strain C3H/AnICs(a)Cs(a) (wild-type), C3H/AnICs(b)Cs(b) and C3H/AnlCs(c)Cs(c) to Okayama University Medical School in Japan. It is known that a point mutation at amino acid 11 (from glutamine to histidine) of acatalasemic mouse catalase and a point mutation at amino acid 439 (from as paragine to serine) of hypocatalasemic mouse catalase are responsible for the catalase deficiency of acatalasemic and hypocatalasemic mice, respectively. Recently, a liver cell line from an acatalasemic mouse andEscherichia coli (E. coli) strains with murine normal, hypocatalasemic, or acatalasemic catalase have been established. The construction of these new systems would be useful for studying the effects of oxidative stress at the cellular level. In this review, we give a brief overview of recent findings of studies in utilizing the catalase-deficient mice and evaluate the possibility of these mouse strains as a candidate animal model for oxidative stress research.
PubMed: 21432086
DOI: 10.1007/BF02897924 -
The Journal of Clinical Investigation Jun 1980To investigate the importance of catalase as a protecting enzyme against oxidative damage in phagocytic leukocytes, we have tested the functional capacity of neutrophils...
To investigate the importance of catalase as a protecting enzyme against oxidative damage in phagocytic leukocytes, we have tested the functional capacity of neutrophils from two individuals homozygous for Swiss-type acatalasemia and from two individuals heterozygous for this deficiency. In the former cells, 25-30% of residual activity of catalase was present. In the latter cells, the values were close to normal. Chemotaxis towards casein, release of lysosomal enzymes and hydrogen peroxide during phagocytosis of zymosan, and intracellular killing of Staphylococcus aureus were normal in all cells tested. Inhibition of heme enzymes with azide (2 mM) enhanced the respiration and hexose monophosphate shunt activity of normal, but not of homozygous acatalasemic, neutrophils. This indicates that the enhancement in normal cells is, at least in part, due to catalase inhibition. After 15 min preincubation with an H(2)O(2)-generating system (glucose plus glucose oxidase), the respiratory response to zymosan phagocytosis was strongly depressed in the homozygous acatalasemic and in normal, azide-treated neutrophils, but not in normal, untreated cells. Under these conditions, the release of lysosomal enzymes was depressed and that of lactate dehydrogenase enhanced, in catalase-deficient and in catalase-inhibited, but not in normal, neutrophils. During prolonged incubation with the H(2)O(2)-generating system (30-60 min), the reduction level of intracellular glutathione remained high and the hexose monophosphate shunt continued to operate normally in all cells tested. Thus, although the function of neutrophils without catalase activity was depressed by extracellular hydrogen peroxide, the H(2)O(2) degradation via the glutathione redox system remained operative. The results indicate that the glutathione redox system by itself efficiently protects phagocytosing neutrophils against their own oxidative products. During heavy external oxidative stress, however, both catalase and the glutathione redox system are needed for adequate protection.
Topics: Catalase; Glutathione; Humans; Metabolism, Inborn Errors; Neutrophils; Oxidation-Reduction; Phagocytosis
PubMed: 7410555
DOI: 10.1172/JCI109817 -
The Journal of Biological Chemistry Jan 2010Reactive oxygen species are known to participate in the regulation of intracellular signaling pathways, including activation of NF-kappaB. Recent studies have indicated...
Reactive oxygen species are known to participate in the regulation of intracellular signaling pathways, including activation of NF-kappaB. Recent studies have indicated that increases in intracellular concentrations of hydrogen peroxide (H(2)O(2)) have anti-inflammatory effects in neutrophils, including inhibition of the degradation of I kappaB alpha after TLR4 engagement. In the present experiments, we found that culture of lipopolysaccharide-stimulated neutrophils and HEK 293 cells with H(2)O(2) resulted in diminished ubiquitination of I kappaB alpha and decreased SCF(beta-TrCP) ubiquitin ligase activity. Exposure of neutrophils or HEK 293 cells to H(2)O(2) was associated with reduced binding between phosphorylated I kappaB alpha and SCF(beta-TrCP) but no change in the composition of the SCF(beta-TrCP) complex. Lipopolysaccharide-induced SCF(beta-TrCP) ubiquitin ligase activity as well as binding of beta-TrCP to phosphorylated I kappaB alpha was decreased in the lungs of acatalasemic mice and mice treated with the catalase inhibitor aminotriazole, situations in which intracellular concentrations of H(2)O(2) are increased. Exposure to H(2)O(2) resulted in oxidative modification of cysteine residues in beta-TrCP. Cysteine 308 in Blade 1 of the beta-TrCP beta-propeller region was found to be required for maximal binding between beta-TrCP and phosphorylated I kappaB alpha. These findings suggest that the anti-inflammatory effects of H(2)O(2) may result from its ability to decrease ubiquitination as well as subsequent degradation of I kappaB alpha through inhibiting the association between I kappaB alpha and SCF(beta-TrCP).
Topics: Acatalasia; Acute Lung Injury; Amitrole; Animals; Catalase; Cells, Cultured; Enzyme Inhibitors; Humans; Hydrogen Peroxide; I-kappa B Proteins; Kidney; Lipopolysaccharides; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Mutant Strains; NF-KappaB Inhibitor alpha; Neutrophils; Oxidants; Phosphorylation; SKP Cullin F-Box Protein Ligases; Ubiquitination
PubMed: 19933270
DOI: 10.1074/jbc.M109.060822 -
The Journal of Biological Chemistry Jun 1977Methoxypolyethylene glycols of 1900 daltons (PEG-1900) or 5000 daltons (PEG-5000) were covalently attached to bovine liver catalase using 2,4,6-trichloro-s-triazine as...
Methoxypolyethylene glycols of 1900 daltons (PEG-1900) or 5000 daltons (PEG-5000) were covalently attached to bovine liver catalase using 2,4,6-trichloro-s-triazine as the coupling agent. Rabbits were immunized by the intravenous and intramuscular routes with catalase modified by covalent attachment of PEG-1900 to 43% of the amino groups (PEG-1900-catalase). The intravenous antiserum did not yield detectable antibodies against PEG-1900-catalase or native catalase, as determined by Ouchterlony and complement fixation methods, whereas the intramuscular antiserum contained antibodies to both PEG-1900-catalase and catalase. PEG-1900 did not react with either antiserum. Catalase was prepared in which PEG-5000 was attached to 40% of the amino groups (PEG-5000-catalase). This catalase preparation did not react with either antiserum. PEG-1900-catalase retained 93% of its enzymatic activity; PEG-5000-catalase retained 95%. PEG-5000-catalase resisted digestion by trypsin, chymotrypsin, and a protease from Streptomyces griseus. PEG-1900-catalase and PEG-5000-catalase exhibited enhanced circulating lives in the blood of acatalasemic mice during repetitive intravenous injections. No evidence was seen of an immune response to injections of the modified enzymes. Mice injected repetitively with PEG-5000-catalase remained immune competent for unmodieied catalase, and no evidence of tissue or organ damage was seen.
Topics: Acatalasia; Animals; Antibody Formation; Catalase; Cattle; Complement Fixation Tests; Hot Temperature; Hydrogen-Ion Concentration; Immunodiffusion; Liver; Mice; Molecular Weight; Peptide Hydrolases; Polyethylene Glycols; Rabbits
PubMed: 16907
DOI: No ID Found -
The Journal of Biological Chemistry Oct 2010Although metabolic conditions associated with an increased AMP/ATP ratio are primary factors in the activation of 5'-adenosine monophosphate-activated protein kinase...
Although metabolic conditions associated with an increased AMP/ATP ratio are primary factors in the activation of 5'-adenosine monophosphate-activated protein kinase (AMPK), a number of recent studies have shown that increased intracellular levels of reactive oxygen species can stimulate AMPK activity, even without a decrease in cellular levels of ATP. We found that exposure of recombinant AMPKαβγ complex or HEK 293 cells to H(2)O(2) was associated with increased kinase activity and also resulted in oxidative modification of AMPK, including S-glutathionylation of the AMPKα and AMPKβ subunits. In experiments using C-terminal truncation mutants of AMPKα (amino acids 1-312), we found that mutation of cysteine 299 to alanine diminished the ability of H(2)O(2) to induce kinase activation, and mutation of cysteine 304 to alanine totally abrogated the enhancing effect of H(2)O(2) on kinase activity. Similar to the results obtained with H(2)O(2)-treated HEK 293 cells, activation and S-glutathionylation of the AMPKα subunit were present in the lungs of acatalasemic mice or mice treated with the catalase inhibitor aminotriazole, conditions in which intracellular steady state levels of H(2)O(2) are increased. These results demonstrate that physiologically relevant concentrations of H(2)O(2) can activate AMPK through oxidative modification of the AMPKα subunit. The present findings also imply that AMPK activation, in addition to being a response to alterations in intracellular metabolic pathways, is directly influenced by cellular redox status.
Topics: AMP-Activated Protein Kinases; Acatalasia; Adenosine Monophosphate; Adenosine Triphosphate; Amitrole; Animals; Catalase; Catalytic Domain; Cell Line; Enzyme Induction; Enzyme Inhibitors; Glutathione; Humans; Hydrogen Peroxide; Mice; Mutation; Oxidants; Oxidation-Reduction; Protein Processing, Post-Translational
PubMed: 20729205
DOI: 10.1074/jbc.M110.143685 -
American Journal of Physiology. Renal... Jun 2004Tissue homeostasis is determined by the balance between oxidants and antioxidants. Catalase is an important antioxidant enzyme regulating the level of intracellular...
Tissue homeostasis is determined by the balance between oxidants and antioxidants. Catalase is an important antioxidant enzyme regulating the level of intracellular hydrogen peroxide and hydroxyl radicals. The effect of catalase deficiency on renal tubulointerstitial injury induced by unilateral ureteral obstruction (UUO) has been studied in homozygous acatalasemic mutant mice (C3H/AnLCs(b)Cs(b)) compared with wild-type mice (C3H/AnLCs(a)Cs(a)). Complete UUO caused interstitial cell infiltration, tubular dilation and atrophy, and interstitial fibrosis with accumulation of type IV collagen in obstructed kidneys (OBK) of both mouse groups. However, the degree of injury showed a significant increase in OBK of acatalasemic mice compared with that of wild-type mice until day 7. The deposition of lipid peroxidation products including 4-hydroxy-2-hexenal, malondialdehyde, and 4-hydroxy-2-nonenal was severer in dilated tubules of acatalasemic OBK. Apoptosis in tubular epithelial cells significantly increased in acatalasemic OBK at day 4. Expression of caspase-9, a marker of mitochondrial pathway-derived apoptosis, increased in dilated tubules of acatalasemic mice. The level of catalase activity remained low in acatalasemic OBK until day 7 without compensatory upregulation of glutathione peroxidase activity. The data indicate that acatalasemia exacerbated oxidation of renal tissue and sensitized tubular epithelial cells to apoptosis in OBK of UUO. This study demonstrates that catalase deficiency enhanced tubulointerstitial injury and fibrosis in a murine model of UUO and thus supports the protective role of catalase in this model.
Topics: Acatalasia; Animals; Apoptosis; Body Weight; Catalase; Epithelial Cells; Fibrosis; Glutathione Peroxidase; Immunohistochemistry; In Situ Nick-End Labeling; Kidney Tubules; Male; Malondialdehyde; Mice; Mice, Inbred C3H; Mice, Knockout; Microscopy, Electron; Nephritis, Interstitial; Organ Size; Oxidative Stress; Thiobarbituric Acid Reactive Substances; Ureteral Obstruction; Xanthine Oxidase
PubMed: 14722014
DOI: 10.1152/ajprenal.00266.2003 -
Journal of Radiation Research Mar 2004The catalase activities in blood and organs of the acatalasemic (C3H/AnLCs(b)Cs(b)) mouse of C3H strain are lower than those of the normal (C3H/AnLCs (a)Cs(a)) mouse. We... (Comparative Study)
Comparative Study
The catalase activities in blood and organs of the acatalasemic (C3H/AnLCs(b)Cs(b)) mouse of C3H strain are lower than those of the normal (C3H/AnLCs (a)Cs(a)) mouse. We examined the effects of prior low-dose (0.5 Gy) X-ray irradiation, which reduced the oxidative damage under carbon tetrachloride-induced hepatopathy in the acatalasemic or normal mice. The acatalasemic mice showed a significantly lower catalase activity and a significantly higher glutathione peroxidase activity compared with those in the normal mice. Moreover, low-dose irradiation increased the catalase activity in the acatalasemic mouse liver to a level similar to that of the normal mouse liver. Pathological examinations and analyses of blood glutamic oxaloacetic and glutamic pyruvic transaminase activity and lipid peroxide levels showed that carbon tetrachloride induced hepatopathy was inhibited by low-dose irradiation. These findings may indicate that the free radical reaction induced by the lack of catalase and the administration of carbon tetrachloride is more properly neutralized by high glutathione peroxidase activity and low-dose irradiation in the acatalasemic mouse liver.
Topics: Acatalasia; Animals; Antioxidants; Carbon Tetrachloride Poisoning; Catalase; Drug Resistance; Glutathione; Lipid Peroxides; Liver; Liver Cirrhosis, Experimental; Mice; Mice, Inbred C3H; Superoxide Dismutase; Transaminases; X-Rays
PubMed: 15133295
DOI: 10.1269/jrr.45.89