ArticleThe Journal of biological chemistry2015
Activation of the UPR protects against cigarette smoke-induced RPE apoptosis through up-regulation of Nrf2.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 76 citations in OpenAlex.
- Molecular Protein Interactions and Predictive Pathways as Biomarkers for Enhancing Volleyball Performance: A Narrative Review.Biomarker insights · 2026Review
- Transmembrane Protein 97 (TMEM97): Molecular Target and Treatment in Age-Related Macular Degeneration (AMD).Biomolecules · 2025Review
- Diabetic retinopathy and Alzheimer's disease: Convergence of the unfolded protein response in neurodegeneration.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Repurposing Dimethyl Fumarate Targeting Nrf2 to Slow Down the Growth of Areas of Geographic Atrophy.International journal of molecular sciences · 2025Review
- Roles of X-box binding protein 1 in liver pathogenesis.Clinical and molecular hepatology · 2025Review
- Article
- Cigarette smoke extract induces ferroptosis in human retinal pigment epithelial cells.Heliyon · 2024Article
- Regulatory factors of Nrf2 in age-related macular degeneration pathogenesis.International journal of ophthalmology · 2024Review
- The endoplasmic reticulum: Homeostasis and crosstalk in retinal health and disease.Progress in retinal and eye research · 2024Review
- Essential Role of XBP1 in Maintaining Photoreceptor Synaptic Integrity in Early Diabetic Retinopathy.Investigative ophthalmology & visual science · 2023Article
- Cigarette smoke causes a bioenergetic crisis in RPE cells involving the downregulation of HIF-1α under normoxia.Cell death discovery · 2023Article
- ERp29 Attenuates Nicotine-Induced Endoplasmic Reticulum Stress and Inhibits Choroidal Neovascularization.International journal of molecular sciences · 2023Article
- Oxidative stress in retinal pigment epithelium degeneration: from pathogenesis to therapeutic targets in dry age-related macular degeneration.Neural regeneration research · 2023Review
- The Role of Nrf2/sMAF Signalling in Retina Ageing and Retinal Diseases.Biomedicines · 2023Review
- Enhanced IRE1α Phosphorylation/Oligomerization-Triggered XBP1 Splicing Contributes to Parkin-Mediated Prevention of SH-SY5Y Cell Death under Nitrosative Stress.International journal of molecular sciences · 2023Article
- Proteostasis in aging-associated ocular disease.Molecular aspects of medicine · 2022Review
- Article
- PERK/EIF2AK3 integrates endoplasmic reticulum stress-induced apoptosis, oxidative stress and autophagy responses in immortalised retinal pigment epithelial cells.Scientific reports · 2022Article
- Phosphorylation at SerThe Journal of biological chemistry · 2022Article
- Cellular stress signaling and the unfolded protein response in retinal degeneration: mechanisms and therapeutic implications.Molecular neurodegeneration · 2022Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Recent studies have revealed a role of endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) in the regulation of RPE cell activity and survival. Herein, we examined the mechanisms by which the UPR modulates apoptotic signaling in human RPE cells challenged with cigarette smoking extract (CSE). Our results show that CSE exposure induced a dose- and time-dependent increase in ER stress markers, enhanced reactive oxygen species (ROS), mitochondrial fragmentation, and apoptosis of RPE cells. These changes were prevented by the anti-oxidant NAC or chemical chaperone TMAO, suggesting a close interaction between oxidative and ER stress in CSE-induced apoptosis. To decipher the role of the UPR, overexpression or down-regulation of XBP1 and CHOP genes was manipulated by adenovirus or siRNA. Overexpressing XBP1 protected against CSE-induced apoptosis by reducing CHOP, p-p38, and caspase-3 activation. In contrast, XBP1 knockdown sensitized the cells to CSE-induced apoptosis, which is likely through a CHOP-independent pathway. Surprisingly, knockdown of CHOP reduced p-eIF2α and Nrf2 resulting in a marked increase in caspase-3 activation and apoptosis. Furthermore, Nrf2 inhibition increased ER stress and exacerbated cell apoptosis, while Nrf2 overexpression reduced CHOP and protected RPE cells. Our data suggest that although CHOP may function as a pro-apoptotic gene during ER stress, it is also required for Nrf2 up-regulation and RPE cell survival. In addition, enhancing Nrf2 and XBP1 activity may help reduce oxidative and ER stress and protect RPE cells from cigarette smoke-induced damage.
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Registered trials
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