Selective formation of certain advanced glycation end products in spinal cord astrocytes of humans and mice with superoxide dismutase-1 mutation

Shibata, Noriyuki; Hirano, Atsushi; Hedley‐Whyte, E. Tessa; Canto, Mauro C. Dal; Nagai, Ryoji; Uchida, Koji; Horiuchi, Seikoh; Kawaguchi, Motoko; Yamamoto, Tomoko; Kobayashi, Makio

doi:10.1007/s00401-002-0537-5

Cited by 50 publications

(44 citation statements)

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“…3) Mutating Trp to Phe also slows the rate of aggregation of recombinant SOD-1 wt following oxidative modification in vitro (25). 4) Oxidative modification of Trp results in the formation of free carbonyl moieties that go on to form advanced glycation end products; carbonyl-containing as well as anionic detergentand dithiothreitol/␤-mercaptoethanol-resistant high molecular weight species of mutant SOD-1 have been detected in cultured cells (2,3) and in both tissues and filter-purified aggregates of transgenic mice expressing mutant SOD-1 (39,40).…”

Section: Discussionmentioning

confidence: 99%

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Tryptophan 32 Potentiates Aggregation and Cytotoxicity of a Copper/Zinc Superoxide Dismutase Mutant Associated with Familial Amyotrophic Lateral Sclerosis

Taylor

Gibbs

Kabashi

et al. 2007

Journal of Biological Chemistry

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One familial form of the neurodegenerative disease, amyotrophic lateral sclerosis, is caused by gain-of-function mutations in the gene encoding copper/zinc superoxide dismutase (SOD-1). This study provides in vivo evidence that normally occurring oxidative modification to SOD-1 promotes aggregation and toxicity of mutant proteins. The oxidation of Trp-32 was identified as a normal modification being present in both wild-type enzyme and SOD-1 with the disease-causing mutation, G93A, isolated from erythrocytes. Mutating Trp-32 to a residue with a slower rate of oxidative modification, phenylalanine, decreased both the cytotoxicity of mutant SOD-1 and its propensity to form cytoplasmic inclusions in motor neurons of dissociated mouse spinal cord cultures. Amyotrophic lateral sclerosis (ALS)5 is an adult onset neurodegenerative disease in which two percent of all cases are caused by mutations in the gene encoding copper/zinc superoxide dismutase (SOD-1) (1). More than 100 mutations distributed throughout the structure of the protein introduce a toxic gain of function that decreases protein solubility, leading to aggregation and the formation of both detergent-insoluble SOD-1 (2, 3) and inclusions that are a histopathological hallmark of ALS (4 -8).The nature of the toxic gain of function imparted by familial ALS (fALS)-causing SOD-1 mutations is not completely understood (reviewed in Ref. 9). These mutations do, however, provide evidence that diverse and relatively minor changes in SOD-1 primary structure can cause fALS. Approximately ninety percent of ALS is sporadic, and it is plausible that posttranslational modification of wild-type proteins affects structural changes analogous to those caused by point mutation (10). Indeed, Lewy body-like inclusions in sporadic ALS are immunoreactive with antibodies to SOD-1 (11-13). It has also been demonstrated that oxidative post-translational modification of SOD-1 occurs in vivo with aging (14) and in association with the fALS (7, 15-17), Parkinson (18), and Alzheimer (18) neurodegenerative diseases. There is also considerable evidence that fALS-causing mutations predispose SOD-1 to post-translational modifications (19 -21), and that in vitro oxidative modification of SOD-1 induces aggregation (22-24).An understanding of how modifications that occur in vivo confer or potentiate toxic properties in proteins is lacking. Given the potential importance of post-translational modification of SOD-1, a study was designed to comprehensively characterize modifications that occur in vivo. Modification-prone residues in wild-type SOD-1 isolated from murine and human erythrocytes were identified and changed to residues that were less likely to be modified. Effects upon survival and aggregation were measured to determine whether preventing modification would attenuate the toxicity of SOD-1 with fALS-causing SOD-1 mutations. Tryptophan 32 (Trp-32) was shown to be modified in a significant fraction of as-isolated SOD-1. Herein we report that changing Trp-32 to a residue with a slower rate ...

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Section: Discussionmentioning

confidence: 99%

“…Oxidative modification of SOD-1 has been observed in Alzheimer, Parkinson, and fALS models (7,(15)(16)(17)(18)(19)(20)40). Such oxidative modification, however, should not be regarded as inherently toxic.…”

Section: Discussionmentioning

confidence: 99%

Tryptophan 32 Potentiates Aggregation and Cytotoxicity of a Copper/Zinc Superoxide Dismutase Mutant Associated with Familial Amyotrophic Lateral Sclerosis

Taylor

Gibbs

Kabashi

et al. 2007

Journal of Biological Chemistry

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“…AGEs have been detected in the spinal cord and brain of ALS patients [17] and are involved in the crosslinking of neurofilament proteins. Indeed, the levels of various AGEs are higher in the Cu,Zn-SOD mutant of human and mice [18]. The relation between glycation and neurodegenerative diseases has been extensively reviewed [56].…”

Section: Protein Glycation and Oxidative Stress In Neurodegenerative mentioning

confidence: 99%

“…Various glycated proteins such as collagen [4], lens crystalline [5], albumin [6], and ribonuclease [7] are also involved in the development of diabetes and aging. β2 Microglobulin was also found to be glycated in patients with hemodialysis-associated amyloidosis [8] as well as some proteins related to neurodegenerative disorders [9] such as Alzheimer's disease (AD) [10][11][12][13], Parkinson's disease (PD) [14][15][16] and Amyotrophic lateral sclerosis (ALS) [17][18][19]. In the above neurodegenerative disorders, AGEs including Nε-(carboxylmethyl) lysine (CML) accumulate but our data also indicated that the levels of Amadori products at the early stage of glycation, were also increased.…”

Section: Glycation Of Proteinsmentioning

confidence: 99%

Glycation vs. glycosylation: a tale of two different chemistries and biology in Alzheimer’s disease

et al. 2016

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In our previous studies, we reported that the activity of an anti-oxidant enzyme, Cu,Zn-superoxide dismutase (Cu,Zn-SOD) became decreased as the result of glycation in vitro and in vivo. Glycated Cu,Zn-SOD produces hydroxyl radicals in the presence of transition metals due to the formation of a Schiff base adduct and a subsequent Amadori product. This results in the site-specific cleavage of the molecule, followed by random fragmentation. The glycation of other anti-oxidant enzymes such as glutathione peroxidase and thioredoxin reductase results in a loss or decrease in enzyme activity under pathological conditions, resulting in oxidative stress. The inactivation of anti-oxidant enzymes induces oxidative stress in aging, diabetes and neurodegenerative disorders. It is well known that the levels of Amadori products and N(e)-(carboxylmethyl)lysine (CML) and other carbonyl compounds are increased in diabetes, a situation that will be discussed by the other authors in this special issue. We and others, reported that the glycation products accumulate in the brains of patients with Alzheimer's disease (AD) patients as well as in cerebrospinal fluid (CSF), suggesting that glycation plays a pivotal role in the development of AD. We also showed that enzymatic glycosylation is implicated in the pathogenesis of AD and that oxidative stress is also important in this process. Specific types of glycosylation reactions were found to be up- or downregulated in AD patients, and key AD-related molecules including the amyloid-precursor protein (APP), tau, and APP-cleaving enzymes were shown to be functionally modified as the result of glycosylation. These results suggest that glycation as well as glycosylation are involved in oxidative stress that is associated with aging, diabetes and neurodegenerative diseases such as AD.

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“…Glycation of these lysine residues impairs the self-assembly process and thereby promotes cross-linking in the neurofilament protein, which leads to ALS. Studies have revealed that AGE levels were higher in the presence of the Cu, Zn-SOD-1mutation, while in control human and mouse subjects, AGE immunoreactivities were virtually absent [67]. Strikingly, the levels of soluble RAGE (sRAGE), a C-terminal truncated isoform of RAGE, are significantly lower in the serum of ALS patients [68].…”

Section: Glycation In Amyotrophic Lateral Sclerosismentioning

confidence: 99%

The role of advanced glycation end products in various types of neurodegenerative disease: a therapeutic approach

Salahuddin

Rabbani

Khan

2014

Cellular and Molecular Biology Letters

148

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of advanced glycation end products; ROS -reactive oxygen species; SNCA -synuclein alpha; sRAGE -soluble receptor of advanced glycation end products; TTR -transthyretin; TKtransketolase; TNF -tumor necrosis factor-α; TPP -thiamine pyrophosphate Review THE ROLE OF ADVANCED GLYCATION END PRODUCTS IN VARIOUS TYPES OF NEURODEGENERATIVE DISEASE:A THERAPEUTIC APPROACH Abstract: Protein glycation is initiated by a nucleophilic addition reaction between the free amino group from a protein, lipid or nucleic acid and the carbonyl group of a reducing sugar. This reaction forms a reversible Schiff base, which rearranges over a period of days to produce ketoamine or Amadori products. The Amadori products undergo dehydration and rearrangements and develop a cross-link between adjacent proteins, giving rise to protein aggregation or advanced glycation end products (AGEs). A number of studies Unauthenticated Download Date | 5/11/18 1:17 PM

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Selective formation of certain advanced glycation end products in spinal cord astrocytes of humans and mice with superoxide dismutase-1 mutation

Cited by 50 publications

References 44 publications

Tryptophan 32 Potentiates Aggregation and Cytotoxicity of a Copper/Zinc Superoxide Dismutase Mutant Associated with Familial Amyotrophic Lateral Sclerosis

Tryptophan 32 Potentiates Aggregation and Cytotoxicity of a Copper/Zinc Superoxide Dismutase Mutant Associated with Familial Amyotrophic Lateral Sclerosis

Glycation vs. glycosylation: a tale of two different chemistries and biology in Alzheimer’s disease

The role of advanced glycation end products in various types of neurodegenerative disease: a therapeutic approach

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