Endoplasmic reticulum stress promotes amyloid-beta peptides production in RGC-5 cells

Bingqian Liu, Yingting Zhu, Jiayi Zhou, Yantao Wei, Chongde Long, Mengfei Chen, Yunlan Ling, Jian Ge, Yehong Zhuo

Research output: Contribution to journalArticlepeer-review

Abstract

Endoplasmic reticulum (ER) stress has been implicated in various neurodegenerative diseases, including Alzheimer’s disease. We have previously observed amyloid production in the retina of the Tg2576 transgenic mouse model of Alzheimer’s disease. In this study, we used tunicamycin-induced ER stress in RGC-5 cells, a cell line identical to the photoreceptor cell line 661W, to investigate the effect of ER stress on production of amyloid-beta (Abeta) peptides. We found that the mRNA level of amyloid-beta precursor protein (APP) remained stable, while the protein level of amyloid-beta precursor protein (APP) was decreased, the amyloid-beta precursor protein cleaving enzymes beta-site APP-cleaving enzyme 1 and presenilin 1 were upregulated, Abeta1–40 and Abeta1–42 production were increased, and reactive oxygen species production and apoptosis markers were elevated following induction of ER stress. The protein level of Abeta degradation enzymes, neprilysin, endothelin-converting enzyme 1, and endothelin-converting enzyme 2 remained unchanged during the prolonged ER stress, showing that the generation of Abeta did not result from reduction of proteolysis by these enzymes. Inclusion of group II caspase inhibitor, Z-DEVD-FMK, increased the ER stress mediated Abeta production, suggesting that they are generated by a caspase-independent mechanism. Our findings provided evidence of a role of ER stress in Abeta peptide overproduction and apoptotic pathway activation in RGC-5 cells.

Original languageEnglish (US)
JournalCell Stress and Chaperones
Volume19
Issue number6
DOIs
StatePublished - Nov 2014
Externally publishedYes

Keywords

  • Amyloid-beta peptide
  • Amyloid-beta precursor protein
  • Endoplasmic reticulum stress
  • Enzymes beta-site APP-cleaving enzyme 1
  • Presenilin 1
  • RGC-5 cells

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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