ArticleDiabetologia2011
Differential regulation of adaptive and apoptotic unfolded protein response signalling by cytokine-induced nitric oxide production in mouse pancreatic beta cells.
Article in Diabetologia, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 67 citations in OpenAlex.
- Review
- Integrative Multi-PTM Proteomics Reveals Dynamic Global, Redox, Phosphorylation, and Acetylation Regulation in Cytokine-Treated Pancreatic Beta Cells.Molecular & cellular proteomics : MCP · 2024Article
- Compound A attenuates proinflammatory cytokine-induced endoplasmic reticulum stress in beta cells and displays beneficial therapeutic effects in a mouse model of autoimmune diabetes.Cellular and molecular life sciences : CMLS · 2022Article
- An accomplice more than a mere victim: The impact of β-cell ER stress on type 1 diabetes pathogenesis.Molecular metabolism · 2021Review
- Adipocyte-derived extracellular vesicles regulate survival and function of pancreatic β cells.JCI insight · 2021Article
- Suppressed anti-inflammatory heat shock response in high-risk COVID-19 patients: lessons from basic research (inclusive bats), light on conceivable therapies.Clinical science (London, England : 1979) · 2020Review
- The Endoplasmic Reticulum and Calcium Homeostasis in Pancreatic Beta Cells.Endocrinology · 2020Review
- Contribution of Oxidative Stress and Impaired Biogenesis of Pancreatic β-Cells to Type 2 Diabetes.Antioxidants & redox signaling · 2019Article
- Article
- Phlda3 regulates beta cell survival during stress.Scientific reports · 2019Article
- Role of Endoplasmic Reticulum Stress in Proinflammatory Cytokine-Mediated Inhibition of Trophoblast Invasion in Placenta-Related Complications of Pregnancy.The American journal of pathology · 2019Article
- Dexamethasone during pregnancy impairs maternal pancreatic β-cell renewal during lactation.Endocrine connections · 2019Article
- A novel inhibitor of inducible NOS dimerization protects against cytokine-induced rat beta cell dysfunction.British journal of pharmacology · 2018Article
- SERCA control of cell death and survival.Cell calcium · 2018Review
- Endoplasmic reticulum stress induced by lipopolysaccharide is involved in the association between inflammation and autophagy in INS‑1 cells.Molecular medicine reports · 2017Article
- Cell Signaling and Stress Responses.Cold Spring Harbor perspectives in biology · 2016Review
- Hypoxia reduces ER-to-Golgi protein trafficking and increases cell death by inhibiting the adaptive unfolded protein response in mouse beta cells.Diabetologia · 2016Article
- Interferon-γ-Induced Unfolded Protein Response in Conjunctival Goblet Cells as a Cause of Mucin Deficiency in Sjögren Syndrome.The American journal of pathology · 2016Article
- ER stress and the decline and fall of pancreatic beta cells in type 1 diabetes.Upsala journal of medical sciences · 2016Review
- A small molecule induces integrin β4 nuclear translocation and apoptosis selectively in cancer cells with high expression of integrin β4.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisPro-inflammatory cytokines such as IL-1β, IFN-γ and TNF-α may contribute to pancreatic beta cell destruction in type 1 diabetes. A mechanism requiring nitric oxide, which is generated by inducible nitric oxide synthase (iNOS), in cytokine-induced endoplasmic reticulum (ER) stress and apoptosis has been proposed. Here, we tested the role of nitric oxide in cytokine-induced ER stress and the subsequent unfolded protein response (UPR) in beta cells.
methodsIsolated islets from wild-type and iNos (also known as Nos2) knockout (iNos ( -/- )) mice, and MIN6 beta cells were incubated with IL-1β, IFN-γ and TNF-α for 24-48 h. N (G)-methyl-L: -arginine was used to inhibit nitric oxide production in MIN6 cells. Protein levels and gene expression were assessed by western blot and real-time RT-PCR.
resultsIn islets and MIN6 cells, inhibition of nitric oxide production had no effect on the generation of ER stress by cytokines, as evidenced by downregulation of Serca2b (also known as Atp2a2) mRNA and increased phosphorylation of PKR-like ER kinase, Jun N-terminal kinase (JNK) and eukaryotic translation initiation factor 2 α subunit. However, nitric oxide regulated the pattern of UPR signalling, which delineates the cellular decision to adapt to ER stress or to undergo apoptosis. Inhibition of nitric oxide production led to reduced expression of pro-apoptotic UPR markers, Chop (also known as Ddit3), Atf3 and Trib3. In contrast, adaptive UPR markers (chaperones, foldases and degradation enhancers) were increased. Further analysis of mouse islets showed that cytokine-induced Chop and Atf3 expression was also dependent on JNK activity. CONCLUSIONS/
interpretationThe mechanism by which cytokines induce ER stress in mouse beta cells is independent of nitric oxide production. However, nitric oxide may regulate the switch between adaptive and apoptotic UPR signalling.
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