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Biochimica Et Biophysica Acta Apr 2016Alloxan induces oxidative stress and hyperglycemia in animal models. Acatalasemic (catalase deficiency) mice are susceptible to alloxan-induced hyperglycemia. As the...
BACKGROUND
Alloxan induces oxidative stress and hyperglycemia in animal models. Acatalasemic (catalase deficiency) mice are susceptible to alloxan-induced hyperglycemia. As the incidence of hyperglycemia induced by alloxan was reportedly improved when mice were fed a vitamin E supplemented diet, this protective effect was examined.
METHODS
Acatalasemic and normal mice fed a vitamin E supplemented diet were treated with alloxan. The pancreas were examined with microscopy. We also isolated pancreatic islets of normal mice treated with alloxan. The glucose stimulated insulin secretion was examined.
RESULTS
Vitamin E powerfully ameliorated the increase in apoptosis. Vitamin E increases insulin amounts secreted from pancreatic cells, but does not ameliorate the regulation of the glucose stimulated insulin secretion.
CONCLUSIONS
It is suggested that the difference in the mice fed vitamin E supplemented diet is due to an increase of insulin secretion and that vitamin E supplementation may have a role in helping to slow the stages of diabetes mellitus.
Topics: Acatalasia; Alloxan; Animals; Apoptosis; Hyperglycemia; Insulin; Male; Mice; Pancreas; Vitamin E
PubMed: 26723540
DOI: 10.1016/j.bbadis.2015.12.022 -
The American Journal of Pathology Dec 1986Biologic, morphologic, and biochemical investigations performed in 2 patients demonstrate multiple peroxisomal deficiencies in the cerebrohepatorenal syndrome of...
Multiple peroxisomal enzymatic deficiency disorders. A comparative biochemical and morphologic study of Zellweger cerebrohepatorenal syndrome and neonatal adrenoleukodystrophy.
Biologic, morphologic, and biochemical investigations performed in 2 patients demonstrate multiple peroxisomal deficiencies in the cerebrohepatorenal syndrome of Zellweger (CHRS) and neonatal adrenoleukodystrophy (NALD). Very long chain fatty acids, abnormal bile acids, including bile acid precursors (di- and trihydroxycoprostanoic acids), and C29-dicarboxylic acid accumulated in plasma in both patients. Generalized hyperaminoaciduria was also present. Peroxisomes could not be detected in CHRS liver and kidney; however, in the NALD patient, small and sparse cytoplasmic bodies resembling altered peroxisomes were found in hepatocytes. Hepatocellular and Kupffer cell lysosomes were engorged with ferritin and contained clefts and trilaminar structures believed to represent very long chain fatty acids. Enzymatic deficiencies reflected the peroxisomal defects. Hepatic glycolate oxidase and palmitoyl-CoA oxidase activities were deficient. No particle-bound catalase was found in cultured fibroblasts, and ether glycerolipid (plasmalogen) biosynthesis was markedly reduced. Administration of phenobarbital and clofibrate, an agent that induces peroxisomal proliferation and enzymatic activities, to the NALD patient did not bring about any changes in plasma metabolites, liver peroxisome population, or oxidizing activities.
Topics: Acatalasia; Acyl-CoA Oxidase; Acyltransferases; Adrenoleukodystrophy; Alcohol Oxidoreductases; Bile Acids and Salts; Brain Diseases; D-Amino-Acid Oxidase; Diffuse Cerebral Sclerosis of Schilder; Fatty Acids; Hepatorenal Syndrome; Humans; Infant; Infant, Newborn; Kidney Diseases; Kupffer Cells; Microbodies; Microscopy, Electron; Oxidoreductases; Phospholipids
PubMed: 2879480
DOI: No ID Found -
Infection and Immunity Apr 1993We obtained a catalase-deficient (Kat-) strain of Neisseria gonorrhoeae isolated from a patient who had been unsuccessfully treated with penicillin. Quantitative enzyme...
We obtained a catalase-deficient (Kat-) strain of Neisseria gonorrhoeae isolated from a patient who had been unsuccessfully treated with penicillin. Quantitative enzyme assays and electrophoresis of cell extracts on native polyacrylamide gels subsequently stained for catalase and peroxidase activities failed to detect both enzymes. The strain exhibited no growth anomalies or unusual requirements when grown under ordinary laboratory conditions. However, the Kat- strain proved extremely sensitive to exogenous hydrogen peroxide, and analysis of the bacterial DNA after such exposure showed extensive single-strand breakage in both chromosomal and plasmid DNAs. Partial characterization of the gonococcal catalase from a Kat+ laboratory strain revealed that the enzyme had the physical and chemical properties of both catalase and peroxidase.
Topics: Acatalasia; DNA Damage; DNA, Bacterial; Hydrogen Peroxide; Neisseria gonorrhoeae; Peroxidases
PubMed: 8454325
DOI: 10.1128/iai.61.4.1232-1238.1993 -
The Journal of Clinical Investigation Mar 1995Pathogenic microorganisms possess antioxidant defense mechanisms for protection from reactive oxygen metabolites such as hydrogen peroxide (H2O2), which are generated...
Pathogenic microorganisms possess antioxidant defense mechanisms for protection from reactive oxygen metabolites such as hydrogen peroxide (H2O2), which are generated during the respiratory burst of phagocytic cells. These defense mechanisms include enzymes such as catalase, which detoxify reactive oxygen species, and DNA repair systems which repair damage resulting from oxidative stress. To determine the relative importance of these two potentially protective defense mechanisms against oxidative stress encountered by Salmonella during infection of the host, a Salmonella typhimurium double mutant unable to produce either the HPI or HPII catalase was constructed, and compared with an isogenic recA mutant deficient in DNA repair. The recA mutant was hypersusceptible to H2O2 at low cell densities in vitro, while the catalase mutant was more susceptible to high H2O2 concentrations at high cell densities. The catalase mutant was found to be resistant to macrophages and retained full murine virulence, in contrast to the recA mutant which previously was shown to be macrophage-sensitive and attenuated in mice. These observations suggest that Salmonella is subjected to low concentrations of H2O2 while at relatively low cell density during infection, conditions requiring an intact DNA repair system but not functional catalase activity.
Topics: Acatalasia; Animals; Base Sequence; Catalase; DNA Repair; Escherichia coli Proteins; Female; Hydrogen Peroxide; Macrophages; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Oxidative Stress; Salmonella typhimurium; Survival Analysis
PubMed: 7883952
DOI: 10.1172/JCI117750 -
The Journal of Biological Chemistry May 2004Studies using the nematode Caenorhabditis elegans as a model system to investigate the aging process have implicated the insulin/insulin-like growth factor-I signaling...
Studies using the nematode Caenorhabditis elegans as a model system to investigate the aging process have implicated the insulin/insulin-like growth factor-I signaling pathway in the regulation of organismal longevity through its action on a subset of target genes. These targets can be classified into genes that shorten or extend life-span upon their induction. Genes that shorten life-span include a variety of stress response genes, among them genes encoding catalases; however, no evidence directly implicates catalases in the aging process of nematodes or other organisms. Using genetic mutants, we show that lack of peroxisomal catalase CTL-2 causes a progeric phenotype in C. elegans. Lack of peroxisomal catalase also affects the developmental program of C. elegans, since Deltactl-2 mutants exhibit decreased egg laying capacity. In contrast, lack of cytosolic catalase CTL-1 has no effect on either nematode aging or egg laying capacity. The Deltactl-2 mutation also shortens the maximum life-span of the long lived Deltaclk-1 mutant and accelerates the onset of its egg laying period. The more rapid aging of Deltactl-2 worms is apparently not due to increased carbonylation of the major C. elegans proteins, although altered peroxisome morphology in the Deltactl-2 mutant suggests that changes in peroxisomal function, including increased production of reactive oxygen species, underlie the progeric phenotype of the Deltactl-2 mutant. Our findings support an important role for peroxisomal catalase in both the development and aging of C. elegans and suggest the utility of the Deltactl-2 mutant as a convenient model for the study of aging and the human diseases acatalasemia and hypocatalasemia.
Topics: Aging; Animals; Caenorhabditis elegans; Catalase; DNA, Complementary; Gene Expression Regulation, Developmental; Green Fluorescent Proteins; Lipid Metabolism; Luminescent Proteins; Microscopy, Confocal; Microscopy, Electron; Models, Genetic; Mutation; Open Reading Frames; Peptides; Peroxisomes; Phenotype; Progeria; Time Factors
PubMed: 14996832
DOI: 10.1074/jbc.M400207200 -
Genetics Jul 1993The enzyme catalase protects aerobic organisms from oxygen-free radical damage by converting hydrogen peroxide to molecular oxygen and water before it can decompose to...
The enzyme catalase protects aerobic organisms from oxygen-free radical damage by converting hydrogen peroxide to molecular oxygen and water before it can decompose to form the highly reactive hydroxyl radical. Hydroxyl radicals are the most deleterious of the activated oxygen intermediates found in aerobic organisms. If formed, they can react with biological molecules in their proximity; the ensuing damage has been implicated in the increasing risk of disease and death associated with aging. To study further the regulation and role of catalase we have undertaken a molecular characterization of the Drosophila catalase gene and two potentially acatalasemic alleles. We have demonstrated that a previously existing allele, Catn4, likely contains a null mutation, a mutation which blocks normal translation of the encoded mRNA. The Catn1 mutation appears to cause a significant change in the protein sequence; however, it is unclear why this change leads to a nonfunctioning protein. Viability of these acatalasemic flies can be restored by transformation with the wild-type catalase gene; hence, we conclude that the lethality of these genotypes is due solely to the lack of catalase. The availability of flies with transformed catalase genes has allowed us to address the effect of catalase levels on aging in Drosophila. Though lack of catalase activity caused decreased viability and life span, increasing catalase activity above wild-type levels had no effect on normal life span.
Topics: Acatalasia; Alleles; Amino Acid Sequence; Animals; Base Sequence; Catalase; Cloning, Molecular; DNA; Drosophila melanogaster; Female; Male; Molecular Sequence Data; Mutation; Transformation, Genetic
PubMed: 8349109
DOI: 10.1093/genetics/134.3.781 -
The Journal of Biological Chemistry Sep 1987We have investigated the genetic control of murine catalase expression by analyzing catalase transcription and translation products from the tissues of control (Csa) and...
We have investigated the genetic control of murine catalase expression by analyzing catalase transcription and translation products from the tissues of control (Csa) and acatalasemic (Csb) mouse strains. Csb animals possess nearly normal catalase enzyme activity levels in liver, while displaying approximately 20 and 1% of normal activity levels in kidney and red blood cells, respectively. Immunoblot analyses of catalase in these tissues have revealed reduced levels of immunologically reactive catalase protein in Csb kidney and red blood cells, paralleling the reduction of catalase enzyme activity in these tissues. In order to determine the molecular basis for Csb acatalasemia, we have isolated a cDNA clone for murine catalase and have used this probe to analyze Csa and Csb genomic DNA and catalase mRNA. These studies have revealed: 1) no restriction fragment length polymorphisms between Csa and Csb genomic DNAs; 2) no differences in the levels of Csa and Csb catalase mRNA within a single tissue; and 3) no differences in the sizes of Csa and Csb catalase mRNAs. These observations suggest that the genetic defect that produces the tissue-specific reduction of catalase expression in Csb mice is not due to a marked rearrangement of DNA within the Csb catalase structural gene. Furthermore, the Csb mutation does not act at the level of gene transcription or mRNA stability, but rather at the level of mRNA translation and/or catalase protein turnover.
Topics: Acatalasia; Amino Acid Sequence; Animals; Base Sequence; Catalase; Cloning, Molecular; DNA; Liver; Mice; Mice, Inbred Strains; Mice, Mutant Strains; Molecular Sequence Data; Mutation; Nucleic Acid Hybridization; Plasmids; Rats
PubMed: 3654595
DOI: No ID Found -
The Tohoku Journal of Experimental... May 1977Catalase activity in leucocytes was found to be half the normal value in hypocatalasemia and extremely low in acatalasemia. Glucose-6-phosphate dehydrogenase activity in...
Catalase activity in leucocytes was found to be half the normal value in hypocatalasemia and extremely low in acatalasemia. Glucose-6-phosphate dehydrogenase activity in erythrocytes was not significantly different between normal, hypocatalasemia and acatalasemia in three families of acatalasemia, but in one family lower activities than normal were found in hypocatalasemia and actalasemia erythrocytes. Other enzyme activities in blood, such as alkaline phosphatase, lactate dehydrogenase, glutamic oxaloacetic and glutamic pyruvic transaminases were not significantly different between normal subjects, hypocatalasemia and acatalasemia.
Topics: Catalase; Erythrocytes; Female; Glucosephosphate Dehydrogenase; Humans; Leukocytes; Male
PubMed: 918959
DOI: 10.1620/tjem.122.93 -
The Journal of Clinical Investigation Apr 1983These studies were performed to test the hypothesis that ether link cleavage (ELC) is an important pathway for the metabolism of thyroxine (T(4)) in the phagocytosing...
These studies were performed to test the hypothesis that ether link cleavage (ELC) is an important pathway for the metabolism of thyroxine (T(4)) in the phagocytosing human leukocyte. When tyrosyl ring-labeled [(125)I]T(4)([Tyr(125)I]T(4)) was incubated with phagocytosing leukocytes, 50% of the degraded label was converted into [(125)I]3,5-diiodotyrosine ([(125)I]DIT). Of the remaining [Tyr(125)I]T(4) that was degraded, two-thirds was recovered as [(125)I]-nonextractable iodine ([(125)I]NEI), and one-third as [(125)I]iodide. The production of [(125)I]DIT was not observed when phenolic ring-labeled [(125)I]T(4) ([Phen(125)I]T(4)) was used, although [(125)I]NEI and [(125)I]iodide were produced. None of these iodinated compounds were formed in leukocytes that were not carrying out phagocytosis. The fraction of T(4) degraded by ELC was decreased by the addition of unlabeled T(4) and by preheating the leukocytes, findings which suggested that the process was enzymic in nature. ELC was enhanced by the catalase inhibitor aminotriazole, and was inhibited by the peroxidase inhibitor propylthiouracil, suggesting that the enzyme is a peroxidase and that hydrogen peroxide (H(2)O(2)) is a necessary cofactor in the reaction. To test this hypothesis, studies were performed in several inherited leukocytic disorders. ELC was not observed in the leukocytes of patients with chronic granulomatous disease, in which the respiratory burst that accompanies phagocytosis is absent. ELC was normal in the leukocytes of two subjects homozygous for Swiss-type acatalasemia, and aminotriazole enhanced ELC in these cells to an extent not significantly different from that observed in normal cells. ELC was normal in the leukocytes of a patient with myeloperoxidase deficiency, but could be induced by the incubation of [Tyr(125)I]T(4) with H(2)O(2) and horseradish peroxidase in the absence of leukocytes. The in vivo occurrence of ELC in the rat was confirmed by demonstrating the appearance of [(125)I]DIT in serum from parenterally injected [(125)I]3,5-diiodothyronine, but no [(125)I]DIT was produced when [(125)I]3',5'-diiodothyronine was administered. FROM THESE FINDINGS WE CONCLUDE THE FOLLOWING: (a) ELC is the major pathway for the degradation of T(4) during leukocyte phagocytosis, and accounts for 50% of the disposal of this iodothyronine; (b) the NEI and iodide formed by phagocytosing cells are derived from the degradation of the phenolic and tyrosyl rings of T(4), although ELC per se accounts for only a small fraction of these iodinated products; (c) the process by which ELC occurs is enzymic in nature, and its occurrence requires the presence of the respiratory burst that accompanies phagocytosis; (d) the enzyme responsible for ELC is likely to be a peroxidase, although a clear role for myeloperoxidase as the candidate enzyme remains to be established; (e) iodothyronines are also degraded by ELC in vivo, and the quantitative importance of this pathway in various pathophysiological states requires further investigation.
Topics: Amitrole; Animals; Catalase; Chromatography, Gel; Chromatography, Ion Exchange; Diiodotyrosine; Ethers; Granulomatous Disease, Chronic; Horseradish Peroxidase; Humans; Hydrogen Peroxide; Male; Metabolism, Inborn Errors; Phagocytes; Phagocytosis; Propylthiouracil; Rats; Thyroxine
PubMed: 6833495
DOI: 10.1172/jci110848 -
The Tohoku Journal of Experimental... Dec 1974
Topics: Acatalasia; Animals; Antigen-Antibody Reactions; Catalase; Cell-Free System; Deoxycholic Acid; Immune Sera; Immunologic Techniques; Leucine; Liver; Mice; Microsomes, Liver
PubMed: 4617335
DOI: 10.1620/tjem.114.349