The aryl hydrocarbon receptor reduces LC3II expression and controls endoplasmic reticulum stress
| Autor: | Kashmira Prasade, Jason Matthews, Fangyi Shi, Hussein Traboulsi, Necola Guerrina, Noof Aloufi, David H. Eidelman, Carolyn J. Baglole, Qutayba Hamid, Caitlin Mehrotra |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Pulmonary and Respiratory Medicine Programmed cell death Physiology Mice 03 medical and health sciences 0302 clinical medicine Protein Phosphatase 1 Physiology (medical) Autophagy Animals Lung Mice Knockout A549 cell biology Chemistry Endoplasmic reticulum Cell Biology BECN1 Fibroblasts respiratory system Endoplasmic Reticulum Stress Aryl hydrocarbon receptor respiratory tract diseases Cell biology 030104 developmental biology Gene Expression Regulation Receptors Aryl Hydrocarbon 030220 oncology & carcinogenesis Unfolded protein response biology.protein Microtubule-Associated Proteins MAP1LC3B Transcription Factor CHOP |
| Zdroj: | American Journal of Physiology-Lung Cellular and Molecular Physiology. 320:L339-L355 |
| ISSN: | 1522-1504 1040-0605 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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