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PubMed: 19251756

Title
Amyloid-dependent triosephosphate isomerase nitrotyrosination induces glycation and tau fibrillation.
Journal
Brain : a journal of neurology
Volume
132
Issue
None
Pages
1335-45
Date
2009-05-01
Authors
Guix FX | Muñoz FJ | Bravo R | Coma M | Fernàndez-Busquets X | Ill-Raga G | Miscione GP | Nakaya T | Suzuki T | Valverde MA | Villà-Freixa J | de Fabritiis G | de Strooper B

Evidence d6210a82fd
JSON

Taupositive material was present in the immunoprecipitates indicating that tau becomes associated to nitroTPI in an Ab dose-dependent pattern (Fig. 5A).TPI and nitro-TPI were incubated with tau protein and samples were analysed by Atomic Force Microscopy (Fig. 7A–D) and TEM (Fig. 7F and G). Abundant paired helical filament-like structures were found in samples containing nitro-TPI plus tau

a(CHEBI:"amyloid-beta") positiveCorrelation complex(p(HGNC:MAPT), p(INTERPRO:"Triosephosphate isomerase", pmod(NO))) View Subject | View Object

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p(HGNC:MAPT) association p(INTERPRO:"Triosephosphate isomerase", pmod(NO)) View Subject | View Object

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complex(p(HGNC:MAPT), p(INTERPRO:"Triosephosphate isomerase", pmod(NO))) positiveCorrelation a(CHEBI:"amyloid-beta") View Subject | View Object

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p(INTERPRO:"Triosephosphate isomerase", pmod(NO)) association p(HGNC:MAPT) View Subject | View Object

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Evidence 1d555de3c0
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In accordance with the decreased efficiency of nitro-TPI we found a significant increase in methylglyoxal production (P50.05), independent of whether DHAP or GAP was used as substrate (Fig. 2E). Thus, nitrotyrosination of TPI results in reduced catalytic activity and increased occupancy of the enzyme by the substrate, and consequently, a higher production of the toxic methylglyoxal.

a(CHEBI:methylglyoxal) negativeCorrelation act(p(INTERPRO:"Triosephosphate isomerase")) View Subject | View Object

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act(p(INTERPRO:"Triosephosphate isomerase")) negativeCorrelation a(CHEBI:methylglyoxal) View Subject | View Object

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Evidence d8f8ea74a0
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Triosephosphate isomerase (TPI) is a key enzyme in cell metabolism that controls the glycolytic flow and energy production through the interconversion of dihydroxyacetone phosphate (DHAP) and D-glyceraldehyde 3-phosphate (G3P) (Richard, 1993). Notably, TPI is the only glycolytic enzyme whose functional deficiency is associated to neurodegeneration (Eber et al., 1991; Ovadi et al., 2004). In particular, inefficient glycolysis (Hoyer et al., 1988) and ATP depletion (Keil et al., 2004) are characteristic in Alzheimer’s disease brains.

a(HBP:Neurodegeneration) negativeCorrelation act(p(INTERPRO:"Triosephosphate isomerase")) View Subject | View Object

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bp(GO:"canonical glycolysis") negativeCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

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act(p(INTERPRO:"Triosephosphate isomerase")) increases rxn(reactants(a(CHEBI:"dihydroxyacetone phosphate")), products(a(CHEBI:"D-glyceraldehyde 3-phosphate"))) View Subject | View Object

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act(p(INTERPRO:"Triosephosphate isomerase")) negativeCorrelation a(HBP:Neurodegeneration) View Subject | View Object

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path(MESH:"Alzheimer Disease") negativeCorrelation bp(GO:"canonical glycolysis") View Subject | View Object

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Evidence 0be8de226a
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Ab induced nitro-oxidative stress on human neuroblastoma cells, resulting in nitrotyrosination of TPI. Moreover, higher levels of nitro-TPI were also detected in extracts from hippocampus (Fig. 1F) and frontal cortex (Fig. 1G) obtained from Alzheimer’s disease brains, compared with healthy subjects.

p(INTERPRO:"Triosephosphate isomerase", pmod(NO, Tyr, 164)) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

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Annotations
Uberon
frontal cortex
Uberon
hippocampal formation
Disease Ontology (DO)
Alzheimer's disease

p(INTERPRO:"Triosephosphate isomerase", pmod(NO, Tyr, 208)) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:
Annotations
Uberon
frontal cortex
Uberon
hippocampal formation
Disease Ontology (DO)
Alzheimer's disease

path(MESH:"Alzheimer Disease") positiveCorrelation p(INTERPRO:"Triosephosphate isomerase", pmod(NO, Tyr, 164)) View Subject | View Object

Appears in Networks:
Annotations
Uberon
frontal cortex
Uberon
hippocampal formation
Disease Ontology (DO)
Alzheimer's disease

path(MESH:"Alzheimer Disease") positiveCorrelation p(INTERPRO:"Triosephosphate isomerase", pmod(NO, Tyr, 208)) View Subject | View Object

Appears in Networks:
Annotations
Uberon
frontal cortex
Uberon
hippocampal formation
Disease Ontology (DO)
Alzheimer's disease

Evidence 6c14c2ac78
JSON

Nitration of Tyr164 and Tyr208 would destabilize the closed state of loop 6 because the interaction between Tyr208 and Ala176 through an H-bond would be compromised (Fig. 2A and B; Supplementary Fig. S2). Indeed, purified TPI after nitrotyrosination with a peroxynitrite donor (SIN-1) displayed a significant decrease in isomerase activity in both directions of the catalysis, i.e. using DHAP (Fig. 2C) or GAP (Fig. 2D) as substrate.

p(INTERPRO:"Triosephosphate isomerase", pmod(NO, Tyr, 164)) decreases act(p(INTERPRO:"Triosephosphate isomerase")) View Subject | View Object

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p(INTERPRO:"Triosephosphate isomerase", pmod(NO, Tyr, 208)) decreases act(p(INTERPRO:"Triosephosphate isomerase")) View Subject | View Object

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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.