a(CHEBI:peroxynitrite) causesNoChange act(p(FPLX:ERK))

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PubMed:16816118

In the present study we injected bilaterally 3-morpholino-sydnonimine (SIN-1), a recognized and widely used peroxynitrite donor (25–30), into rat hippocampus, and investigated whether or not peroxynitrite could induce simultaneously nitration and hyperphosphorylation of tau and the underlying mechanisms in vivo. The level of nitrated and hyperphosphorylated tau was markedly increased in rat hippocampus 24 h, and prevented by preinjection of uric acid, a natural scavenger of peroxynitrite. GSK-3beta and p38 MAPKs, including p38alpha, p38beta, and p38delta activity was increased, but no change in the activity of p38gamma, ERK, and c-Jun amino-terminal kinase (JNK). Both nitrated tau and hyperphosphorylated tau were aggregated in the hippocampus, with activity of 20S proteasome significantly arrested in SIN-1-injected rats. Hyperphosphorylated tau was degraded as efficiently as normal tau by 20S proteasome, but the nitrated tau with an unorderly secondary structure became more resistant to the proteolysis, providing evidence that peroxynitrite simultaneously induces tau hyperphosphorylation, nitration, and accumulation, and that activation of GSK-3beta, p38alpha, p38beta, p38delta isoforms and the inhibition of proteasome activity are respectively responsible for the peroxynitrite-induced tau hyperphosphorylation and accumulation.

Related Edges 15

• a(CHEBI:linsidomine) increases a(CHEBI:peroxynitrite)
• a(CHEBI:linsidomine) decreases act(p(HBP:"20 S Proteasome"))
• a(CHEBI:peroxynitrite) increases p(RGD:Mapt, pmod(Ph))
• a(CHEBI:peroxynitrite) increases p(RGD:Mapt, pmod(HBP:nitration))
• a(CHEBI:peroxynitrite) increases act(p(RGD:Gsk3b))
• a(CHEBI:peroxynitrite) increases act(p(RGD:Mapk14))
• a(CHEBI:peroxynitrite) increases act(p(RGD:Mapk11))
• a(CHEBI:peroxynitrite) increases act(p(RGD:Mapk13))
• a(CHEBI:peroxynitrite) causesNoChange act(p(RGD:Mapk12))
• a(CHEBI:peroxynitrite) causesNoChange act(p(FPLX:JNK))
• a(CHEBI:peroxynitrite) increases bp(GO:"neurofibrillary tangle assembly")
• bp(GO:"neurofibrillary tangle assembly") negativeCorrelation act(p(HBP:"20 S Proteasome"))
• act(p(HBP:"20 S Proteasome")) negativeCorrelation p(RGD:Mapt, pmod(HBP:nitration))
• act(p(HBP:"20 S Proteasome")) negativeCorrelation bp(GO:"neurofibrillary tangle assembly")
• p(RGD:Mapt, pmod(HBP:nitration)) negativeCorrelation act(p(HBP:"20 S Proteasome"))

Uberon

hippocampal formation

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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.

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