Excitotoxin-induced neuronal death is associated with response of a unique intracellular aspartic proteinase, cathepsin E

Kazuyoshi Tominaga, Hiroshi Nakanishi, Yoshiyuki Yasuda, Kenji Yamamoto

Research output: Contribution to journalArticle

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Abstract

Excitotoxicity produced by excessive stimulation of glutamate receptors is known to lead to neuronal lesion and death: Here, we demonstrate that quantitative and qualitative changes in cathepsin E (CE) gene products are associated with execution of the excitotoxic neuronal death. Intracerebroventricular injection of kainate (KA) resulted in marked elevation of both mRNA and protein levels of CE in the rat hippocampal CA3 region, where the enzyme was mainly found in vulnerable neurons and activated microgila. Northern blot analysis showed that the size of the transcript for CE was identical with that normally expressed in rat spleen. Immunoblot analysis, however, revealed the predominant occurrence of the highly modified CE species, besides the mature CE. This polypeptide was distinct from the mature CE in molecular masses (106 vs. 82 kDa) and pl (6.4-7.3 vs. 5.0-5.5) and showed resistance to conversion into the enzymatically active form by acid treatment. Consistent with these in vivo results, administration of glutamate to primary cultured rat hippocampal neurons resulted in a marked expression of this novel CE species. These data indicate that excessive stimulation of glutamate receptors causes induction of the CE gene response followed by persistent expression of CE in the novel form, besides its mature form, predominantly in the hippocampal neurons.

Original languageEnglish
Pages (from-to)2574-2584
Number of pages11
JournalJournal of Neurochemistry
Volume71
Issue number6
Publication statusPublished - Dec 1 1998

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Cathepsin E
Aspartic Acid Proteases
Neurotoxins
Neurons
Rats
Glutamate Receptors
Genes
Hippocampal CA3 Region
Kainic Acid
Molecular mass
Northern Blotting
Glutamic Acid
Spleen

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Excitotoxin-induced neuronal death is associated with response of a unique intracellular aspartic proteinase, cathepsin E. / Tominaga, Kazuyoshi; Nakanishi, Hiroshi; Yasuda, Yoshiyuki; Yamamoto, Kenji.

In: Journal of Neurochemistry, Vol. 71, No. 6, 01.12.1998, p. 2574-2584.

Research output: Contribution to journalArticle

Tominaga, Kazuyoshi ; Nakanishi, Hiroshi ; Yasuda, Yoshiyuki ; Yamamoto, Kenji. / Excitotoxin-induced neuronal death is associated with response of a unique intracellular aspartic proteinase, cathepsin E. In: Journal of Neurochemistry. 1998 ; Vol. 71, No. 6. pp. 2574-2584.
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