Cerebrospinal fluid levels of superoxide dismutases in neurological diseases detected by sensitive enzyme immunoassays

Yoshida, Eiji; Mokuno, Kenji; Aoki, Shinjiro; Takahashi, Akira; Riku, S; Murayama, Tomoyuki; Yanagi, Tsutomu; Kato, Kanefusa

doi:10.1016/0022-510x(94)90006-x

Cited by 50 publications

(32 citation statements)

References 26 publications

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“…There are benefits to having peptides from the same regions: 1) a pair of analogous peptides behaving similarly can increase the confidence level of H/D exchange behaviors of the region and 2) a pair of analogous peptides enables the sublocalization of deuteriums. For example, the subtraction of the number of deuteriums in segment [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] (30,31). The average deuteration level at each segment was obtained using the deuteration levels at 15, 50, 150, and 500 s. The H/D exchange experiments of both fully metallated and partially metallated copper/zinc WT SOD1 were repeated on three different days, and the standard deviation was typically 2% or less with the exception of the segment containing residues 133-144, whose standard deviation was 5%, suggesting that variation in electrostatic loop structure and dynamics is an intrinsic property of SOD1.…”

Section: Resultsmentioning

confidence: 99%

“…The sites of modification were not determined, although previous studies showed SOD residues Trp 32 (24) (29). To 3 l of 1.0 mg/ml SOD1 (in 20 mM potassium phosphate buffer, 150 mM potassium chloride, pH 7.2) was added 17 l of phosphate-buffered saline (in D 2 O, pD 7.2), to initiate the exchange reactions, so that H/D exchange took place at 10 M SOD1 near the in vivo concentration (30,31). The samples were incubated at 4°C for a predetermined time of 15, 50, 150, and 500 s. The reaction mixture was quenched by the addition of 30 l of cold 2 M guanidine hydrochloride, 1 M tris(2-carboxyethyl)phosphine, pH 1.4.…”

Section: Methodsmentioning

confidence: 99%

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A Common Property of Amyotrophic Lateral Sclerosis-associated Variants

Molnar¹,

Karabacak

Johnson

et al. 2009

Journal of Biological Chemistry

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At least 119 mutations in the gene encoding copper/zinc superoxide dismutase (SOD1) cause amyotrophic lateral sclerosis by an unidentified toxic gain of function. We compared the dynamic properties of 13 as-isolated, partially metallated, SOD1 variant enzymes using hydrogen-deuterium exchange. We identified a shared property of these familial amyotrophic lateral sclerosis-related SOD1 variants, namely structural and dynamic change affecting the electrostatic loop (loop VII) of SOD1. Furthermore, SOD1 variants that have severely compromised metal binding affinities demonstrated additional structural and dynamic changes to the zinc-binding loop (loop IV) of SOD1. Although the biological consequences of increased loop VII mobility are not fully understood, this common property is consistent with the hypotheses that SOD1 mutations exert toxicity via aggregation or aberrant association with other cellular constituents.At least 119 mutations in the gene encoding copper/zinc superoxide dismutase cause fALS 3 by introducing an unknown toxic gain of function. Numerous hypotheses have been proposed to explain mechanisms of SOD1 variant toxicity (reviewed in Refs. 2 and 3). Proposed hypotheses to define the structural or functional alterations shared by SOD1 variants include: 1) decreased stability of apo (metal-deficient) or metallated SOD1 (4), 2) increased hydrophobicity (5), 3) increased self-aggregation propensity (6), 4) increased susceptibility to post-translational modification, 5) decreased metal affinity (7), 6) destabilization of the SOD1 native dimer, and 7) aberrant copper-mediated chemistry (8). The literature, as a whole, supports the notion that the aforementioned hypotheses are in fact related, because SOD1 metal content, native disulfide bond status, hydrophobicity, and stability are interrelated (2) and may thereby affect the specificity of copper-mediated chemistry (9) and aggregation propensity.Proposed hypotheses to explain the biological consequences of SOD1 toxicity include: 1) impairment of axonal transport (10), 2) excitotoxicity (11), 3) impairment of proteasome (12) or chaperone activity (13), and 4) mitochondrial (14, 15) or endoplasmic reticulum-Golgi dysfunction (15). The relationship of mutation-associated structural changes of SOD1 with these downstream effects is not well established. SOD1 aggregation has been implicated as a contributor to mitochondrial (15, 16), endoplasmic reticulum-Golgi (15, 17, 18), proteasome (19), and chaperone (13) dysfunction and thus bridges the conceptual gap between mutation-related changes to the physicochemical properties of SOD1 and the varied cellular consequences of SOD1 mutations. Indeed, the only property shared by all fALS SOD1 variants thus far studied is an increased propensity to form proteinaceous aggregates of SOD1, as evidenced in fALS patients (20, 21), 21 rodent lines of 13 different SOD1 mutations (22), and at least 13 fALS mutations in cell culture models. Moreover, proteinaceous SOD1-containing inclusions were also found in a subset of spora...

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

A Common Property of Amyotrophic Lateral Sclerosis-associated Variants

Molnar¹,

Karabacak

Johnson

et al. 2009

Journal of Biological Chemistry

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“…Furthermore, Sudha et al [32] indicated no significant change in erythrocyte SOD activity of PD patients, while Marttila et al [33] showed unaltered SOD activity in peripheral blood leukocytes of PD patients compared to the control group. On the other hand, Yoshida et al [34] reported increased Mn SOD activity in the cerebrospinal fluid (CSF) of PD patients, whereas Marttila et al [33] indicated no difference between parkinsonian and normal CSF in terms of SOD activity. Peripheral studies of SOD activity were discordant, but postmortem studies demonstrated selectively increased activity of cytosolic [33] and particulate [35] fractions of SOD in the substantia nigra of PD patients.…”

Section: Discussionmentioning

confidence: 99%

Peripheral Blood Markers of Oxidative Stress in Parkinson’s Disease

et al. 2007

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Oxidative stress and generation of reactive oxygen species are believed to be implicated in Parkinson’s disease (PD). Erythrocyte activity of superoxide dismutase (SOD) and catalase, the blood glutathione system, and plasma levels of thiobarbituric-acid-reactive substances (TBARS) were measured in 80 PD patients. These biochemical parameters were also measured in 29 age-matched controls. Patients with PD had significantly higher red blood corpuscle (RBC) activity of SOD. The mean RBC activity of catalase in PD patients did not differ significantly from those of controls. RBC catalase activity was significantly lower in advanced cases of PD compared to early cases. Oxidized glutathione was significantly higher in RBCs of PD patients, although there were no changes in total glutathione and reduced glutathione compared to controls. TBARS content was increased in patients with PD. Levodopa therapy, age and duration of illness did not significantly influence the measured parameters. Our study supports the previous hypothesis that oxidative stress is implicated in the pathogenesis of PD. Perspectives for treatment of PD in the future could include antioxidant therapy.

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“…Studies with recombinant mutant SODs have shown that some but not others have a decreased specific activity [5][6][7]. Similarly, in red cells of affected individuals, SOD activity varies from 30% normal to within the normal range [2,[8][9][10][11] and both active mutant homoand heterodimers of a charge change variant can be detected [4]. These observations, in conjunction with the finding that transgenic mice expressing FALS mutant as well as their normal SOD develop motor neuron disease [12,13], are strong evidence that a gain in function rather than a loss of ability to dismutate superoxide is responsible for the disease.…”

Section: Introductionmentioning

confidence: 99%

Decreased thermal stability of red blood cellglu¹⁰⁰→gly superoxide dismutase from a family with amyotrophic lateral sclerosis

1995

FEBS Letters

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Familial amyotrophic lateral sclerosis is a degenerative motor neuron disease associated in some cases with the presence of a mutant form of Cu/Zn snperoxide dismutase. We have studied the stability of the gly 1°°--~ glu mutant in extracts of red cells obtained from members of a family with a history of the disease. Extracts containing the mutant had an average 68% of normal superoxide dismutase activity. On heating at 65°C, these extracts lost activity at twice the rate of extracts containing only the normal enzyme. Decreased heat stability was also evident on native polyacrylamide gel electrophoresis with activity staining. This showed selective loss of first the mutant homodimer and then the heterodimer of the enzyme. Decreased stability intracellularly could be a factor in motor neuron degeneration.

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Cerebrospinal fluid levels of superoxide dismutases in neurological diseases detected by sensitive enzyme immunoassays

Cited by 50 publications

References 26 publications

A Common Property of Amyotrophic Lateral Sclerosis-associated Variants

A Common Property of Amyotrophic Lateral Sclerosis-associated Variants

Peripheral Blood Markers of Oxidative Stress in Parkinson’s Disease

Decreased thermal stability of red blood cellglu¹⁰⁰→gly superoxide dismutase from a family with amyotrophic lateral sclerosis

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Cerebrospinal fluid levels of superoxide dismutases in neurological diseases detected by sensitive enzyme immunoassays

Cited by 50 publications

References 26 publications

A Common Property of Amyotrophic Lateral Sclerosis-associated Variants

A Common Property of Amyotrophic Lateral Sclerosis-associated Variants

Peripheral Blood Markers of Oxidative Stress in Parkinson’s Disease

Decreased thermal stability of red blood cellglu100→gly superoxide dismutase from a family with amyotrophic lateral sclerosis

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Decreased thermal stability of red blood cellglu¹⁰⁰→gly superoxide dismutase from a family with amyotrophic lateral sclerosis