PMID- 33236922
OWN - NLM
STAT- MEDLINE
DCOM- 20210323
LR  - 20210323
IS  - 1522-1504 (Electronic)
IS  - 1040-0605 (Linking)
VI  - 320
IP  - 3
DP  - 2021 Mar 1
TI  - The aryl hydrocarbon receptor reduces LC3II expression and controls endoplasmic 
      reticulum stress.
PG  - L339-L355
LID - 10.1152/ajplung.00122.2020 [doi]
AB  - The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor 
      whose physiological function is poorly understood. The AhR is highly expressed in 
      barrier organs such as the skin, intestine, and lung. The lungs are continuously 
      exposed to environmental pollutants such as cigarette smoke (CS) that can induce 
      cell death mechanisms such as apoptosis, autophagy, and endoplasmic reticulum 
      (ER) stress. CS also contains toxicants that are AhR ligands. We have previously 
      shown that the AhR protects against apoptosis, but whether the AhR also protects 
      against autophagy or ER stress is not known. Using cigarette smoke extract (CSE) 
      as our in vitro surrogate of environmental tobacco exposure, we first assessed 
      the conversion of LC3I to LC3II, a classic feature of both autophagic and ER 
      stress-mediated cell death pathways. LC3II was elevated in CSE-exposed lung 
      structural cells [mouse lung fibroblasts (MLFs), MLE12 and A549 cells] when AhR 
      was absent. However, this heightened LC3II expression could not be explained by 
      increased expression of key autophagy genes (Gabarapl1, Becn1, Map1lc3b), 
      upregulation of upstream autophagic machinery (Atg5-12, Atg3), or impaired 
      autophagic flux, suggesting that LC3II may be autophagy independent. This was 
      further supported by the absence of autophagosomes in Ahr(-/-) lung cells. 
      However, Ahr(-/-) lung cells had widespread ER dilation, elevated expression of 
      the ER stress markers CHOP and GADD34, and an accumulation of ubiquitinated 
      proteins. These findings collectively illustrate a novel role for the AhR in 
      attenuating ER stress by a mechanism that may be autophagy independent.
FAU - Guerrina, Necola
AU  - Guerrina N
AD  - Research Institute of the McGill University Health Centre, McGill University, 
      Montreal, Quebec, Canada.
AD  - Department of Pathology, McGill University, Montreal, Quebec, Canada.
FAU - Aloufi, Noof
AU  - Aloufi N
AD  - Research Institute of the McGill University Health Centre, McGill University, 
      Montreal, Quebec, Canada.
AD  - Department of Pathology, McGill University, Montreal, Quebec, Canada.
FAU - Shi, Fangyi
AU  - Shi F
AD  - Research Institute of the McGill University Health Centre, McGill University, 
      Montreal, Quebec, Canada.
AD  - Department of Pathology, McGill University, Montreal, Quebec, Canada.
FAU - Prasade, Kashmira
AU  - Prasade K
AD  - Research Institute of the McGill University Health Centre, McGill University, 
      Montreal, Quebec, Canada.
FAU - Mehrotra, Caitlin
AU  - Mehrotra C
AD  - Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, 
      Canada.
FAU - Traboulsi, Hussein
AU  - Traboulsi H
AD  - Research Institute of the McGill University Health Centre, McGill University, 
      Montreal, Quebec, Canada.
AD  - Department of Medicine, McGill University, Montreal, Quebec, Canada.
FAU - Matthews, Jason
AU  - Matthews J
AD  - Department of Nutrition, University of Oslo, Oslo, Norway.
AD  - Department of Pharmacology and Toxicology, University of Toronto, Toronto, 
      Ontario, Canada.
FAU - Eidelman, David H
AU  - Eidelman DH
AD  - Research Institute of the McGill University Health Centre, McGill University, 
      Montreal, Quebec, Canada.
AD  - Department of Medicine, McGill University, Montreal, Quebec, Canada.
FAU - Hamid, Qutayba
AU  - Hamid Q
AD  - Research Institute of the McGill University Health Centre, McGill University, 
      Montreal, Quebec, Canada.
AD  - Department of Medicine, McGill University, Montreal, Quebec, Canada.
AD  - College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.
FAU - Baglole, Carolyn J
AU  - Baglole CJ
AD  - Research Institute of the McGill University Health Centre, McGill University, 
      Montreal, Quebec, Canada.
AD  - Department of Pathology, McGill University, Montreal, Quebec, Canada.
AD  - Department of Medicine, McGill University, Montreal, Quebec, Canada.
AD  - Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, 
      Canada.
LA  - eng
GR  - 162273/Gouvernement du Canada | CIHR | Institute of Health Services and Policy 
      Research (IHSPR)/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201125
PL  - United States
TA  - Am J Physiol Lung Cell Mol Physiol
JT  - American journal of physiology. Lung cellular and molecular physiology
JID - 100901229
RN  - 0 (Ddit3 protein, mouse)
RN  - 0 (Map1lc3b protein, mouse)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 147336-12-7 (Transcription Factor CHOP)
RN  - EC 3.1.3.16 (Ppp1r15a protein, mouse)
RN  - EC 3.1.3.16 (Protein Phosphatase 1)
SB  - IM
MH  - Animals
MH  - Autophagy
MH  - *Endoplasmic Reticulum Stress
MH  - Fibroblasts/*metabolism
MH  - *Gene Expression Regulation
MH  - Lung/*metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Microtubule-Associated Proteins/*biosynthesis/genetics
MH  - Protein Phosphatase 1/genetics/metabolism
MH  - Receptors, Aryl Hydrocarbon/genetics/*metabolism
MH  - Transcription Factor CHOP/genetics/metabolism
OTO - NOTNLM
OT  - COPD
OT  - ER stress
OT  - autophagy
OT  - cigarette smoke
OT  - fibroblasts
EDAT- 2020/11/26 06:00
MHDA- 2021/03/24 06:00
CRDT- 2020/11/25 12:13
PHST- 2020/11/26 06:00 [pubmed]
PHST- 2021/03/24 06:00 [medline]
PHST- 2020/11/25 12:13 [entrez]
AID - 10.1152/ajplung.00122.2020 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2021 Mar 1;320(3):L339-L355. doi: 
      10.1152/ajplung.00122.2020. Epub 2020 Nov 25.