A New Type of Inherited Catalase Deficiencies: Its Characterization and Comparison to the Japanese and Swiss Type of Acatalasemia

Góth, László

doi:10.1006/bcmd.2001.0415

Cited by 34 publications

(10 citation statements)

References 25 publications

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“…35 The phenotypes of these individuals are generally normal with one reported exception: Japanese subjects with profound deficiency (acatalasemia) have oral ulcerations. 36 A recent report identified a series of mutations in a Hungarian kindred with catalase deficiency (GA insertion in exon 2, G insertion in exon 2, and T3 G substitution in intron 7) associated with adverse lipid profiles and a high incidence (12.7%) of familial diabetes mellitus.…”

Section: Antioxidant Enzymesmentioning

confidence: 99%

Oxidative Enzymopathies and Vascular Disease

Leopold

Loscalzo

2005

ATVB

174

117

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Abstract-In the vasculature, reactive oxygen species (ROS) generated by both mitochondrial respiration and enzymatic sources serve as integral components of cellular signaling and homeostatic mechanisms. Because ROS are highly reactive biomolecules, the cellular redox milieu is carefully maintained by small-molecule antioxidants and antioxidant enzymes to prevent the deleterious consequences of ROS excess. When this redox balance is perturbed, because of either increased ROS production or decreased antioxidant capacity, oxidant stress is increased in the vessel wall and, if not offset, vascular dysfunction ensues. A number of heritable polymorphisms of pro-oxidant enzymes, including 5-lipoxygenase, cyclooxygenase-2, nitric oxide synthase-3, and NAD(P)H oxidase, have been identified and found to modulate ROS production and, thereby, the risk of atherothrombotic cardiovascular disease in individuals with these genetic polymorphisms. Similarly, heritable deficiency of the antioxidant enzymes catalase, glutathione peroxidases, glutathione-S-transferases, heme oxygenase, and glucose-6-phosphate dehydrogenase favors ROS accumulation, and has been associated with an increased risk of vascular disease. Individually, each of these polymorphisms imposes a state of uncompensated oxidant stress on the vasculature and collectively comprise the oxidative enzymopathies. Key Words: antioxidants Ⅲ atherosclerosis Ⅲ genetic polymorphism Ⅲ reactive oxygen species C ellular respiration in an oxygen-rich environment generates abundant derivatives of partially reduced oxygen, collectively termed reactive oxygen species (ROS). Under basal conditions, ROS serve as an integral component of cellular signaling pathways; however, when these highly reactive metabolic products are in excess, they impose an oxidant stress on the cellular environment, which, in turn, modifies biomolecules to modulate cell and organism phenotype. 1 To protect against cellular oxidant stress and its adverse sequelae, adaptive enzymatic mechanisms have evolved to metabolize ROS into less reactive forms and minimize their potential to produce oxidative damage and cellular dysfunction.The importance of maintaining a balance between ROS production and metabolism is highlighted when there is deficiency or dysfunction of vascular antioxidant enzymes. This results in a net accumulation of ROS because of decreased antioxidant capacity in the setting of ambient ROS production by vascular sources. Recent interest has focused on heritable polymorphisms of vascular antioxidant enzymes as one mechanism by which antioxidant capacity is diminished. These polymorphisms have been associated with an increased risk of vascular disease in both animal models and human studies and collectively may be recognized as oxidative enzymopathies. Vascular Sources of ROSUnder basal conditions, superoxide anion, a 1-electron reduction product of oxygen, is the primary source from which Original

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Section: Antioxidant Enzymesmentioning

confidence: 99%

Oxidative Enzymopathies and Vascular Disease

Leopold

Loscalzo

2005

ATVB

174

117

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“…Acatalasemia in Japan, Switzerland, and in Hungary has been characterized by clinical, biochemical, and partially by genetic methods. Other reported cases of acatalasemia are sporadic, poorly characterized, and mainly based on decreased catalase activity [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Detection of a novel familial catalase mutation (Hungarian type D) and the possible risk of inherited catalase deficiency for diabetes mellitus

Góth

Vitai

Rass³

et al. 2005

ELECTROPHORESIS

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The enzyme catalase is the main regulator of hydrogen peroxide metabolism. Recent findings suggest that a low concentration of hydrogen peroxide may act as a messenger in some signalling pathways whereas high concentrations are toxic for many cells and cell components. Acatalasemia is a genetically heterogeneous condition with a worldwide distribution. Yet only two Japanese and three Hungarian syndrome-causing mutations have been reported. A large-scale (23 130 subjects) catalase screening program in Hungary yielded 12 hypocatalasemic families. The V family with four hypocatalasemics (60.6 +/- 7.6 MU/L) and six normocatalasemic (103.6 +/- 23.5 MU/L) members was examined to define the mutation causing the syndrome. Mutation screening yielded four novel polymorphisms. Of these, three intron sequence variations, namely G-->A at the nucleotide 60 position in intron 1, T-->A at position 11 in intron 2, and G-->T at position 31 in intron 12, are unlikely to be responsible for the decreased blood catalase activity. However, the novel G-->A mutation in exon 9 changes the essential amino acid Arg 354 to Cys 354 and may indeed be responsible for the decreased catalase activity. This inherited catalase deficiency, by inducing an increased hydrogen peroxide steady-state concentration in vivo, may be involved in the early manifestation of type 2 diabetes mellitus for the 35-year old proband.

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“…Subsequently, Swiss and Hungarian acatalasemia-afflicted people were reported, but they did not evidently suffer from the symptomatic features of the disease (2,3). The residual catalase (EC 1.11.1.6) activity in Swiss and Hungarian acatalasemic erythrocytes was found to be higher than in the erythrocytes from the Japanese.…”

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confidence: 99%

Characterization of Acatalasemic Erythrocytes Treated with Low and High Dose Hydrogen Peroxide

Masuoka

Sugiyama

Ishibashi

et al. 2006

Journal of Biological Chemistry

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The effects of hydrogen peroxide on normal and acatalasemic erythrocytes were examined. Severe hemolysis of acatalasemic erythrocytes and a small tyrosine radical signal (g ‫؍‬ 2.005) associated with the formation of ferryl hemoglobin were observed upon the addition of less than 0.25 mM hydrogen peroxide. However, when the concentration of hydrogen peroxide was increased to 0.5 mM, acatalasemic erythrocytes became insoluble in water and increased the tyrosine radical signal. Polymerization of hemoglobin and aggregation of the erythrocytes were observed. On the other hand, normal erythrocytes exhibited only mild hemolysis by the addition of hydrogen peroxide under similar conditions. From these results, the scavenging of hydrogen peroxide by hemoglobin generates the ferryl hemoglobin species (H-Hb-Fe(IV)‫؍‬O) plus protein-based radicals ( ⅐ HbFe(IV)‫؍‬O). These species induce hemolysis of erythrocytes, polymerization of hemoglobin, and aggregation of the acatalasemic erythrocytes. A mechanism for the onset of Takarara disease is proposed.In 1952, Takahara reported that Japanese acatalasemia (catalase deficiency) patients suffered from progressive oral gangrene (Takahara disease) as a result of being infected with hydrogen peroxide-generating bacteria (1). Subsequently, Swiss and Hungarian acatalasemia-afflicted people were reported, but they did not evidently suffer from the symptomatic features of the disease (2, 3). The residual catalase (EC 1.11.1.6) activity in Swiss and Hungarian acatalasemic erythrocytes was found to be higher than in the erythrocytes from the Japanese. Ogata et al. (4) suggested the catalase deficiency in the blood to be the etiological cause of the disease. We became interested in the scavenging of hydrogen peroxide in erythrocytes to understand the metabolism of hydrogen peroxide in acatalasemic erythrocytes. The hydrogen peroxide scavenging rates in normal and acatalasemic mouse and human erythrocytes were examined (5-8). It was found that hydrogen peroxide was dominantly scavenged by hemoglobin in hemolysates of acatalasemic erythrocytes. The scavenging rate was enhanced in the presence of reduced pyridine nucleotides (NAD(P)H) or ascorbic acid (AsA).2 A cyclic process has been proposed for the scavenging mechanism; hydrogen peroxide oxidizes hemoglobin, which is then reduced by NAD(P)H or AsA (8).We suspected that during the process, hemoglobin was oxidized to ferryl hemoglobin (H-Hb-Fe(IV)ϭO) with hydrogen peroxide, and then a comproportionation reaction of Hb-Fe(IV)ϭO and ferrous hemoglobin generated methemoglobin (H-Hb-Fe(III) ϩ ) (9). Methemoglobin was then further oxidized to radicals of ferryl hemoglobin ( ⅐ Hb-Fe(IV)ϭO) with hydrogen peroxide (10). In this study, we report that the oxidized hemoglobin species in the scavenging process were identified and that a novel property of acatalasemic erythrocytes was subjected to hydrogen peroxide treatment; erythrocytes aggregated to be insoluble in water at a high concentration (Ն0.5 mM) of hydrogen peroxide, whereas the severe hemol...

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A New Type of Inherited Catalase Deficiencies: Its Characterization and Comparison to the Japanese and Swiss Type of Acatalasemia

Cited by 34 publications

References 25 publications

Oxidative Enzymopathies and Vascular Disease

Oxidative Enzymopathies and Vascular Disease

Detection of a novel familial catalase mutation (Hungarian type D) and the possible risk of inherited catalase deficiency for diabetes mellitus

Characterization of Acatalasemic Erythrocytes Treated with Low and High Dose Hydrogen Peroxide

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