Transient knockdown of presenilin-1 provokes endoplasmic reticulum stress related formation of autophagosomes in HepG2 cells

Péter Száraz, Gábor Bánhegyi, Paola Marcolongo, Angelo Benedetti

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The involvement of presenilins in the endoplasmic reticulum (ER) related autophagy was investigated by their transient knockdown in HepG2 cells. The silencing of PSEN1 but not of PSEN2 led to cell growth impairment and decreased viability. PSEN1 silencing resulted in ER stress response as evidenced by the elevated levels of glucose regulated protein 78 (Grp78), protein disulfide isomerase (PDI), and CCAAT/enhancer-binding protein homologous protein (CHOP) and by the activation of activating transcription factor 6 (ATF6). The activation of autophagy was indicated by the increased procession of microtubule-associated light chain 3 protein isoform B (LC3B) and by decreased phosphorylation of mammalian target of rapamycin (mTOR) and 70 kDa ribosomal protein S6 kinase (p70S6K). Formation of ER-related cytoplasmic vacuolization colocalizing with the autophagic marker LC3B was also observed. The morphological effects and LC3B activation in presenilin-1 knockdown cells could be prevented by using the phosphoinositide 3-kinase (PI3K) inhibitor wortmannin or by calcium chelation. The results show that presenilin-1 hampers the ER stress dependent initiation of macroautophagy.

Original languageEnglish
Pages (from-to)57-63
Number of pages7
JournalArchives of Biochemistry and Biophysics
Volume538
Issue number2
DOIs
Publication statusPublished - Sep 23 2013

Keywords

  • Autophagy
  • Calcium
  • ER stress
  • Endoplasmic reticulum
  • PI3K
  • Presenilin

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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