Absence of excitotoxicity-induced apoptosis in the hippocampus of mice lacking the Jnk3 gene View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1997-10

AUTHORS

Derek D. Yang, Chia-Yi Kuan, Alan J. Whitmarsh, Mercedes Rinócn, Timothy S. Zheng, Roger J. Davis, Pasko Rakic, Richard A. Flavell

ABSTRACT

Excitatory amino acids induce both acute membrane depolarization and latent cellular toxicity, which often leads to apoptosis in many neurological disorders1,2. Recent studies indicate that glutamate toxicity may involve the c-Jun amino-terminal kinase (JNK) group of mitogen-activated protein (MAP) kinases3,4,5. One member of the JNK family, Jnk3, may be required for stress-induced neuronal apoptosis, as it is selectively expressed in the nervous system6,7. Here we report that disruption of the gene encoding Jnk3 in mice caused the mice to be resistant to the excitotoxic glutamate-receptor agonist kainic acid: they showed a reduction in seizure activity and hippocampal neuron apoptosis was prevented. Although application of kainic acid imposed the same level of noxious stress, the phosphorylation of c-Jun and the transcriptional activity of the AP-1 transcription factor complex were markedly reduced in the mutant mice. These data indicate that the observed neuroprotection is due to the extinction of a Jnk3-mediated signalling pathway, which is animportant component in the pathogenesis of glutamate neurotoxicity. More... »

PAGES

865-870

Journal

TITLE

Nature

ISSUE

6653

VOLUME

389

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/39899

    DOI

    http://dx.doi.org/10.1038/39899

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1035322653

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/9349820


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    36 schema:description Excitatory amino acids induce both acute membrane depolarization and latent cellular toxicity, which often leads to apoptosis in many neurological disorders1,2. Recent studies indicate that glutamate toxicity may involve the c-Jun amino-terminal kinase (JNK) group of mitogen-activated protein (MAP) kinases3,4,5. One member of the JNK family, Jnk3, may be required for stress-induced neuronal apoptosis, as it is selectively expressed in the nervous system6,7. Here we report that disruption of the gene encoding Jnk3 in mice caused the mice to be resistant to the excitotoxic glutamate-receptor agonist kainic acid: they showed a reduction in seizure activity and hippocampal neuron apoptosis was prevented. Although application of kainic acid imposed the same level of noxious stress, the phosphorylation of c-Jun and the transcriptional activity of the AP-1 transcription factor complex were markedly reduced in the mutant mice. These data indicate that the observed neuroprotection is due to the extinction of a Jnk3-mediated signalling pathway, which is animportant component in the pathogenesis of glutamate neurotoxicity.
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