PMID- 23154241
OWN - NLM
STAT- MEDLINE
DCOM- 20130221
LR  - 20181202
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 92
IP  - 1
DP  - 2013 Jan 17
TI  - Endoplasmic reticulum stress in HepG2 cells inhibits apolipoprotein A-I 
      secretion.
PG  - 72-80
LID - S0024-3205(12)00659-5 [pii]
LID - 10.1016/j.lfs.2012.11.001 [doi]
AB  - AIMS: Endoplasmic reticulum (ER) stress modulates gene expression and has been 
      implicated in causing dyslipidemias. To determine if ER stress may contribute to 
      hypoalphalipoproteinemia through suppression of apo A-I gene expression, human 
      hepatoma cell line Hep G2 was treated with ER stress inducers and the changes in 
      apo A-I gene expression were compared to albumin gene expression. MAIN METHODS: 
      HepG2 cells were treated with tunicamycin (TM) and thapsigargin (TG), two potent 
      inducers of ER stress, and apo A-I and albumin protein levels, mRNA levels, and 
      promoter activity were measured. ER stress was measured using the ER 
      stress-responsive alkaline phosphatase assay and by Western blot quantitation of 
      ER stress markers such as glucose-regulated protein-78 (GRP-78), phosphorylated 
      Jun N-terminal kinase (phospho-JNK), total JNK, phosphorylated eukaryotic 
      initiation factor 2 alpha (phospho eIF2alpha), and total eIF2alpha. KEY FINDINGS: TM and 
      TG induced ER stress in HepG2 cells and reduced apo A-I and albumin secretion in 
      a dose-dependent manner. Intracellular albumin levels increased in cells treated 
      with TM and TG while intracellular apo A-I levels decreased. Albumin mRNA and 
      albumin gene promoter activity were reduced in proportion to the decrease in 
      albumin secreted while changes in the apo A-I mRNA levels and promoter activity 
      were modest and did not account for the reduction in apo A-I secretion. 
      SIGNIFICANCE: These results indicate that apo A-I secretion is inhibited by ER 
      stress possibly by affecting cellular degradation pathways. However, ER stress 
      does not affect apo A-I secretion by regulating gene expression.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Naem, Emad
AU  - Naem E
AD  - The Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, 
      University of Florida, Jacksonville College of Medicine, Jacksonville, FL 32209, 
      USA.
FAU - Haas, Michael J
AU  - Haas MJ
FAU - Wong, Norman C W
AU  - Wong NC
FAU - Mooradian, Arshag D
AU  - Mooradian AD
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121112
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Albumins)
RN  - 0 (Apolipoprotein A-I)
RN  - 0 (Biomarkers)
RN  - 0 (RNA, Messenger)
RN  - 11089-65-9 (Tunicamycin)
RN  - 67526-95-8 (Thapsigargin)
SB  - IM
MH  - Albumins/genetics/metabolism
MH  - Apolipoprotein A-I/genetics/*metabolism
MH  - Biomarkers/metabolism
MH  - Blotting, Western
MH  - Dose-Response Relationship, Drug
MH  - Endoplasmic Reticulum Stress/*drug effects
MH  - Gene Expression Regulation/*drug effects
MH  - Hep G2 Cells
MH  - Humans
MH  - Promoter Regions, Genetic/genetics
MH  - RNA, Messenger/metabolism
MH  - Thapsigargin/administration & dosage/*pharmacology
MH  - Tunicamycin/administration & dosage/*pharmacology
EDAT- 2012/11/17 06:00
MHDA- 2013/02/22 06:00
CRDT- 2012/11/17 06:00
PHST- 2012/08/21 00:00 [received]
PHST- 2012/10/03 00:00 [revised]
PHST- 2012/10/30 00:00 [accepted]
PHST- 2012/11/17 06:00 [entrez]
PHST- 2012/11/17 06:00 [pubmed]
PHST- 2013/02/22 06:00 [medline]
AID - S0024-3205(12)00659-5 [pii]
AID - 10.1016/j.lfs.2012.11.001 [doi]
PST - ppublish
SO  - Life Sci. 2013 Jan 17;92(1):72-80. doi: 10.1016/j.lfs.2012.11.001. Epub 2012 Nov 
      12.