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ERBB2-modulated ATG4B and autophagic cell death in human ARPE19 during oxidative stress
- Source :
- PLoS ONE, Vol 14, Iss 3, p e0213932 (2019), PLoS ONE
- Publication Year :
- 2019
- Publisher :
- Public Library of Science (PLoS), 2019.
-
Abstract
- Age-related macular degeneration (AMD) is an ocular disease with retinal degeneration. Retinal pigment epithelium (RPE) degeneration is mainly caused by long-term oxidative stress. Kinase activity could be either protective or detrimental to cells during oxidative stress; however, few reports have described the role of kinases in oxidative stress. In this study, high-throughput screening of kinome siRNA library revealed that erb-b2 receptor tyrosine-protein kinase 2 (ERBB2) knockdown reduced reactive oxygen species (ROS) production in ARPE-19 cells during oxidative stress. Silencing ERBB2 caused an elevation in microtubule associated protein light chain C3-II (MAP1LC3B-II/I) conversion and sequesterone (SQSTM)1 protein level. ERBB2 deprivation largely caused an increase in autophagy-regulating protease (ATG4B) expression, a protease that negatively recycles MAP1LC3-II at the fusion step between the autophagosome and lysosome, suggesting ERBB2 might modulate ATG4B for autophagy induction in oxidative stress-stimulated ARPE-19 cells. ERBB2 knockdown also caused an accumulation of nuclear factor erythroid 2-related factor 2 (NRF2) and enhanced its transcriptional activity. In addition, ERBB2 ablation or treatment with autophagy inhibitors reduced oxidative-induced cytotoxic effects in ARPE-19 cells. Furthermore, ERBB2 silencing had little or no additive effects in ATG5/7-deficient cells. Taken together, our results suggest that ERBB2 may play an important role in modulating autophagic RPE cell death during oxidative stress, and ERBB2 may be a potential target in AMD prevention.
- Subjects :
- 0301 basic medicine
Autophagosome
Retinal degeneration
Receptor, ErbB-2
Autophagy-Related Proteins
Retinal Pigment Epithelium
medicine.disease_cause
Biochemistry
Macular Degeneration
0302 clinical medicine
Medicine and Health Sciences
Small interfering RNAs
Geriatric Ophthalmology
RNA, Small Interfering
skin and connective tissue diseases
Multidisciplinary
Cell Death
Chemistry
Retinal Degeneration
Oxides
Proteases
Peroxides
Enzymes
Cell biology
Nucleic acids
Cysteine Endopeptidases
medicine.anatomical_structure
Cell Processes
Gene Knockdown Techniques
030220 oncology & carcinogenesis
Physical Sciences
Retinal Disorders
Medicine
Research Article
Programmed cell death
NF-E2-Related Factor 2
Autophagic Cell Death
Science
Immunoblotting
ATG5
Molecular Probe Techniques
Library Screening
Research and Analysis Methods
Models, Biological
Cell Line
03 medical and health sciences
Lysosome
Genetics
medicine
Humans
Kinase activity
Non-coding RNA
Molecular Biology Techniques
Molecular Biology
Molecular Biology Assays and Analysis Techniques
Autophagy
Chemical Compounds
Biology and Life Sciences
Proteins
Cell Biology
Hydrogen Peroxide
medicine.disease
Gene regulation
Oxidative Stress
Ophthalmology
030104 developmental biology
Geriatrics
Macular Disorders
Enzymology
RNA
Gene expression
Reactive Oxygen Species
Oxidative stress
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 14
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....3840936aeaa091ddeb12b23c00c15557