Pro-apoptotic protein kinase Cδ is associated with intranuclear inclusions in a transgenic model of Huntington's disease

Evgeny A. Zemskov, Nihar R. Jana, Masaru Kurosawa, Haruko Miyazaki, Naoaki Sakamoto, Munenori Nekooki, Nobuyuki Nukina

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

In order to investigate any effect of truncated mutant huntingtin (tNhtt) aggregation on protein kinase C (PKC) signaling in Huntington's disease (HD), we studied a possible association of PKC isoforms with the aggregates using cellular and transgenic models of HD. In this report we describe an association of mutant tNhtt with at least three PKC isoforms (α, δ, ζ), as revealed by co-immunoprecipitation assays and immunocytochemistry in a cellular model of HD (Neuro2a cells expressing tNhtt-150Q-EGFP), as well as a specific association of PKCδ with intranuclear aggregates in a transgenic model (R6/2 mice). Immunoblot analysis of isolated nuclear fractions shows an elevation of nuclear PKCδ in transgenic brain tissue. The observed elevation has a strong similarity with the apoptotic translocation of PKCδ detected in experiments with the mouse neuroblastoma Neuro2a cells. Using a Neuro2a cell line expressing tNhtt with the nuclear localization signal, we demonstrate the association of PKCδ with intranuclear aggregates'and present evidence that accumulation of PKCδ in cell nuclei does not depend on mutant htt nuclear translocation. Our results suggest that the association of PKCδ with intranuclear htt-aggregates may affect its apoptotic function in a transgenic model of HD.

Original languageEnglish
Pages (from-to)395-406
Number of pages12
JournalJournal of Neurochemistry
Volume87
Issue number2
DOIs
Publication statusPublished - Oct 2003
Externally publishedYes

Keywords

  • Apoptosis
  • Huntingtin
  • Huntington's disease
  • Polyglutamine
  • Protein kinase C
  • Protein kinase Cδ

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Fingerprint

Dive into the research topics of 'Pro-apoptotic protein kinase Cδ is associated with intranuclear inclusions in a transgenic model of Huntington's disease'. Together they form a unique fingerprint.

Cite this