ArticleBritish journal of pharmacology2015
The endoplasmic reticulum stress and the HIF-1 signalling pathways are involved in the neuronal damage caused by chemical hypoxia.
Article in British journal of pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 63 citations in OpenAlex.
- A Brief Description of the Cellular Mechanisms Involved in Cardiac Chemical Hypoxia.Cardiovascular toxicology · 2026Review
- Evaluating TnP as a Potential Therapeutic Agent for Retinopathy in Zebrafish Models.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Progress of research on glucose transporter proteins in hepatocellular carcinoma.World journal of hepatology · 2025Review
- Hepatitis B surface antigen: carcinogenesis mechanisms and clinical implications in hepatocellular carcinoma.Experimental hematology & oncology · 2025Review
- The role of bHLH-PAS transcription factors in endoplasmic reticulum stress.Frontiers in molecular biosciences · 2025Review
- Review
- A narrative review: exploring viral-induced malignancies through the lens of dysregulated cellular metabolism and glucose transporters.BMC cancer · 2024Review
- ER Stress and Mitochondrial Perturbations Regulate Cell Death in Retinal Detachment: Exploring the Role of HIF1α.Investigative ophthalmology & visual science · 2024Article
- Transcriptomic Analyses of Neurotoxic Astrocytes Derived from Adult Triple Transgenic Alzheimer's Disease Mice.Journal of molecular neuroscience : MN · 2023Article
- A β-Cyclodextrin-Based Nanoparticle with Very High Transfection Efficiency Unveils siRNA-Activated TLR3 Responses in Human Prostate Cancer Cells.Pharmaceutics · 2022Article
- Salubrinal Protects Against Cisplatin-Induced Cochlear Hair Cell Endoplasmic Reticulum Stress by Regulating Eukaryotic Translation Initiation Factor 2α Signalling.Frontiers in molecular neuroscience · 2022Article
- Endoplasmic Reticulum Stress and the Unfolded Protein Response in Cerebral Ischemia/Reperfusion Injury.Frontiers in cellular neuroscience · 2022Review
- Dexmedetomidine Protects Human Renal Tubular Epithelial HK-2 Cells against Hypoxia/Reoxygenation Injury by Inactivating Endoplasmic Reticulum Stress Pathway.Cell journal · 2021Article
- IL-6/STAT3 Induced Neuron Apoptosis in Hypoxia by Downregulating ATF6 Expression.Frontiers in physiology · 2021Article
- Protective effect of the extremolytes ectoine and hydroxyectoine in a porcine organ culture.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2020Article
- Differential susceptibility of PC12 and BRL cells and the regulatory role of HIF-1α signaling pathway in response to acute methylmercury exposure under normoxia.Toxicology letters · 2020Article
- Review
- Gestational Hypoxia Inhibits Pregnancy-Induced Upregulation of CaHypertension (Dallas, Tex. : 1979) · 2020Article
- IL13Rα1 protects against rheumatoid arthritis by combating the apoptotic resistance of fibroblast-like synoviocytes.Arthritis research & therapy · 2020Article
- Neuroprotective Effect of the Inhibitor Salubrinal after Cardiac Arrest in a Rodent Model.Oxidative medicine and cellular longevity · 2020Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeHypoxia inducible factor-1 (HIF-1) promotes transitory neuronal survival suggesting that additional mechanisms such as the endoplasmic reticulum (ER) stress might be involved in determining neuronal survival or death. Here, we examined the involvement of ER stress in hypoxia-induced neuronal death and analysed the relationship between ER stress and the HIF-1 pathways. EXPERIMENTAL APPROACH: Cultures of rat cortical neurons were exposed to chemical hypoxia induced by 200 μM CoCl2 , and its effect on neuronal viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and counting apoptotic nuclei. Protein levels were determined by Western blot analysis. RT-PCR was performed to analyse the content and the t1/2 of HIF-1α mRNA. KEY
resultsChemical hypoxia induced neuronal apoptosis in a time-dependent manner and activated the ER stress PRK-like endoplasmic reticulum kinase (PERK)-dependent pathway. At later stages, chemical hypoxia increased the expression of the C/EBP homologous protein (CHOP) and caspase 12 activity. CoCl2 reduced HIF-1α mRNA t1/2 leading to a decrease in HIF-1α mRNA and protein content, simultaneously activating the ER stress PERK-dependent pathway. Salubrinal, a selective inhibitor of phospho-eIF2α phosphatase, protected neurons from chemical hypoxia by reducing CHOP levels and caspase 12 activity, and increasing the t1/2 of HIF-1α mRNA and the levels of HIF-1α protein. Knocking down HIF-1α blocked the neuroprotective effects of salubrinal. CONCLUSIONS AND IMPLICATIONS: Neuronal apoptosis induced by chemical hypoxia is a process regulated by HIF-1α stabilization early on and by ER stress activation at later stages. Our data also suggested that HIF-1α levels were regulated by ER stress.
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