ArticleScientific reports2022
PERK/EIF2AK3 integrates endoplasmic reticulum stress-induced apoptosis, oxidative stress and autophagy responses in immortalised retinal pigment epithelial cells.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- Interplay between NRF2 post-translational modifications and protein-protein interactions: Perspectives from emerging structural and functional evidence.Archives of biochemistry and biophysics · 2026Review
- Palmitate drives mitochondrial and ER stress through disruption of the CD73-Adenosine axis.Research square · 2026Article
- Modulation of mRNA Expression of Biomarkers in the UPR-PERK Pathway by Ellagic Acid in Metabolic Dysfunction-Associated Fatty Liver Disease.International journal of molecular sciences · 2026Article
- GSDME Deficiency Suppresses ER Stress-Induced Autophagic Cell Death via mTOR/S6K1 Activation in Hepatobiliary Carcinomas.Biochemical genetics · 2026Article
- Organelle-specific regulation of ferroptosis.Biology direct · 2026Review
- The intracellular agent of Q fever,mBio · 2025Article
- Endoplasmic reticulum-mitochondria coupling prompts ZBP1-mediated RPE cell PANoptosis in age-related macular degeneration.Communications biology · 2025Article
- Ebselen Alleviates Sepsis-Induced Acute Kidney Injury by Regulating Endoplasmic Reticulum Stress, Apoptosis, and Oxidative Stress.Veterinary medicine and science · 2025Article
- Inhibition of pro-apoptotic UPR pathways PERK/CHOP and IRE1/JNK protects differentiated SH-SY5Y cells against rotenone-induced toxicity.Frontiers in molecular neuroscience · 2025Article
- Signaling Pathways in Retinal Pigment Epithelium (RPE) Cells in Response to Stress Conditions of Age-Related Macular Degeneration (AMD).Advances in experimental medicine and biology · 2025Review
- The protein kinases family in fungi: adaptability, virulence and conservation between species.Frontiers in microbiology · 2025Review
- A large-scale in vivo screen to investigate the roles of human genes in Drosophila melanogaster.G3 (Bethesda, Md.) · 2024Article
- Article
- Identification of autophagy-related genes as potential biomarkers correlated with immune infiltration in bipolar disorder: a bioinformatics analysis.BMC medical genomics · 2024Article
- The endoplasmic reticulum: Homeostasis and crosstalk in retinal health and disease.Progress in retinal and eye research · 2024Review
- Article
- COPI Vesicle Disruption Inhibits Mineralization via mTORC1-Mediated Autophagy.International journal of molecular sciences · 2023Article
- Endoplasmic reticulum stress: molecular mechanism and therapeutic targets.Signal transduction and targeted therapy · 2023Review
- The orally bioavailable GSPT1/2 degrader SJ6986 exhibits in vivo efficacy in acute lymphoblastic leukemia.Blood · 2023Article
- Knockout of PERK protects rat Müller glial cells against OGD-induced endoplasmic reticulum stress-related apoptosis.BMC ophthalmology · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Retinal pigment epithelium (RPE) performs essential functions for ensuring retinal homeostasis and is a key site for pathogenic changes leading to age-related macular degeneration (AMD). Compromised proteostasis in RPE results in ER stress and ER stress-dependent antioxidant, apoptosis and autophagic responses. ER stress induces the unfolded protein response (UPR) in which EIF2AK3, encoding the protein kinase RNA-like ER kinase (PERK), acts as a key regulator. Downregulated EIF2AK3 gene expression has recently been identified in AMD using human donor RPE, however the molecular mechanisms that integrate the various ER-mediated cellular pathways underpinning progressive RPE dysfunction in AMD have not been fully characterised. This study investigated the downstream effects of PERK downregulation in response to Brefeldin A (BFA)-induced ER stress in ARPE-19 cells. PERK downregulation resulted in increased ER stress and impaired apoptosis induction, antioxidant responses and autophagic flux. ARPE-19 cells were unable to efficiently induce autophagy following PERK downregulation and PERK presented a role in regulating the rate of autophagy induction. The findings support PERK downregulation as an integrative event facilitating dysregulation of RPE processes critical to cell survival known to contribute to AMD development and highlight PERK as a potential future therapeutic target for AMD.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.