PMID- 23942054
OWN - NLM
STAT- MEDLINE
DCOM- 20131125
LR  - 20211203
IS  - 1096-0384 (Electronic)
IS  - 0003-9861 (Linking)
VI  - 538
IP  - 2
DP  - 2013 Oct 15
TI  - Transient knockdown of presenilin-1 provokes endoplasmic reticulum stress related 
      formation of autophagosomes in HepG2 cells.
PG  - 57-63
LID - S0003-9861(13)00237-3 [pii]
LID - 10.1016/j.abb.2013.08.003 [doi]
AB  - 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 70kDa 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.
CI  - Copyright (c) 2013 Elsevier Inc. All rights reserved.
FAU - Szaraz, Peter
AU  - Szaraz P
AD  - Department of Molecular and Developmental Medicine, University of Siena, Siena, 
      Italy.
FAU - Banhegyi, Gabor
AU  - Banhegyi G
FAU - Marcolongo, Paola
AU  - Marcolongo P
FAU - Benedetti, Angelo
AU  - Benedetti A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130811
PL  - United States
TA  - Arch Biochem Biophys
JT  - Archives of biochemistry and biophysics
JID - 0372430
RN  - 0 (Endoplasmic Reticulum Chaperone BiP)
RN  - 0 (HSPA5 protein, human)
RN  - 0 (MAP1LC3B protein, human)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Presenilin-1)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - *Autophagy
MH  - Calcium/metabolism
MH  - Cell Proliferation
MH  - Cell Survival
MH  - Endoplasmic Reticulum Chaperone BiP
MH  - *Endoplasmic Reticulum Stress
MH  - Hep G2 Cells/*cytology/metabolism
MH  - Humans
MH  - Microtubule-Associated Proteins/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Presenilin-1/*genetics
MH  - *RNA Interference
OTO - NOTNLM
OT  - Autophagy
OT  - Calcium
OT  - ER stress
OT  - Endoplasmic reticulum
OT  - PI3K
OT  - Presenilin
EDAT- 2013/08/15 06:00
MHDA- 2013/12/16 06:00
CRDT- 2013/08/15 06:00
PHST- 2013/05/28 00:00 [received]
PHST- 2013/07/27 00:00 [revised]
PHST- 2013/08/03 00:00 [accepted]
PHST- 2013/08/15 06:00 [entrez]
PHST- 2013/08/15 06:00 [pubmed]
PHST- 2013/12/16 06:00 [medline]
AID - S0003-9861(13)00237-3 [pii]
AID - 10.1016/j.abb.2013.08.003 [doi]
PST - ppublish
SO  - Arch Biochem Biophys. 2013 Oct 15;538(2):57-63. doi: 10.1016/j.abb.2013.08.003. 
      Epub 2013 Aug 11.