Intracellular Aβ and C99 aggregates induce mitochondria-dependent cell death in human neuroglioma H4 cells through recruitment of the 20S proteasome subunits

Hyo Jin Park, Sang Soo Kim, Seong Man Kang, Hyangshuk Rhim

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Recent studies have reported that neuronal apoptosis is induced not only by extracellular Aβ but also by intracellular Aβ; however, the mechanism by which intracellular Aβ contributes to the regulation of cell death associated with the pathogenesis of AD remains to be elucidated. Using immunological assays and a short-lived enhanced green fluorescent protein (d2EGFP) system, we showed that intracellular Aβ and C99 form perinuclear aggregates in the cytosol, and the resulting aggregates attenuate the activity of the 26S proteasome. In addition, the immunofluorescence assays (IFA) revealed that the 20S proteasome α-subunits are recruited into perinuclear aggregates in both human embryonic kidney (HEK293) and human neuroglioma H4 (H4) cells. Interestingly, we observed an increase in the levels of Bax, cleavage of PARP-1, and mitochondrial release of proapoptotic proteins, such as cytochrome c and HtrA2, in H4 cells with intracellular Aβ or C99 aggregates, but not in HEK293 cells with those aggregates. The results of the present study indicate that intracellular Aβ and C99 aggregates induce mitochondria-dependent apoptotic cell death via elevation of Bax levels as a result of proteasome inhibition in a cell type-specific manner.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalBrain Research
Volume1273
DOIs
Publication statusPublished - 2009 Jun 1

Fingerprint

Proteasome Endopeptidase Complex
Mitochondria
Cell Death
HEK293 Cells
Cytochromes c
Cytosol
Fluorescent Antibody Technique
Apoptosis
Kidney
Proteins

Keywords

  • Alzheimer's disease
  • Amyloid beta (Aβ)
  • C99
  • Human neuroglioma H4 cell
  • Mitochondria-dependent cell death
  • Proteasome

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

Cite this

Intracellular Aβ and C99 aggregates induce mitochondria-dependent cell death in human neuroglioma H4 cells through recruitment of the 20S proteasome subunits. / Park, Hyo Jin; Kim, Sang Soo; Kang, Seong Man; Rhim, Hyangshuk.

In: Brain Research, Vol. 1273, 01.06.2009, p. 1-8.

Research output: Contribution to journalArticle

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