ArticleJournal of cellular and molecular medicine2008
Cytokine-induced beta-cell apoptosis is NO-dependent, mitochondria-mediated and inhibited by BCL-XL.
Article in Journal of cellular and molecular medicine, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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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.
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Who cites it
35 citing papers in PubMed, 61 citations in OpenAlex.
- Mitochondrial dysfunction, cerebral metabolic crisis, and exploratory bioenergetic biomarkers in a translational swine model of acute carbon monoxide poisoning.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Bcl-2 and Bcl-xL in Diabetes: Contributions to Endocrine Pancreas Viability and Function.Biomedicines · 2025Review
- The effect of selenium on the proliferation of bovine endometrial epithelial cells in a lipopolysaccharide-induced damage model.BMC veterinary research · 2024Article
- The effect and mechanism of selenium supplementation on the proliferation capacity of bovine endometrial epithelial cells exposed to lipopolysaccharide in vitro under high cortisol background.Journal of animal science · 2024Article
- BCL-XL Overexpression Protects Pancreatic β-Cells against Cytokine- and Palmitate-Induced Apoptosis.International journal of molecular sciences · 2023Article
- RETRACTED: Deciphering the Potential Neuroprotective Effects of Luteolin against AβInternational journal of molecular sciences · 2021Article
- Clathrin-mediated Endocytosis of Alpha-1 Antitrypsin is Essential for its Protective Function in Islet Cell Survival.Theranostics · 2019Article
- The Association between Depression and Type 1 Diabetes Mellitus: Inflammatory Cytokines as Ferrymen in between?Mediators of inflammation · 2019Review
- Article
- Survival of encapsulated islets: More than a membrane story.World journal of transplantation · 2016Review
- Group VIA Phospholipase A2 (iPLA2β) Modulates Bcl-x 5'-Splice Site Selection and Suppresses Anti-apoptotic Bcl-x(L) in β-Cells.The Journal of biological chemistry · 2015Article
- Diabetes Associated Metabolomic Perturbations in NOD Mice.Metabolomics : Official journal of the Metabolomic Society · 2015Article
- Celastrol ameliorates cytokine toxicity and pro-inflammatory immune responses by suppressing NF-κB activation in RINm5F beta cells.BMB reports · 2015Article
- Cellular Mechanisms of Oxidative Stress and Action in Melanoma.Oxidative medicine and cellular longevity · 2015Review
- Targeting the pancreatic β-cell to treat diabetes.Nature reviews. Drug discovery · 2014Review
- Achillea Millefolium L. Hydro- Alcoholic Extract Protects Pancreatic Cells by Down Regulating IL- 1β and iNOS Gene Expression in Diabetic Rats.International journal of molecular and cellular medicine · 2014Article
- Cellular stress response and innate immune signaling: integrating pathways in host defense and inflammation.Journal of leukocyte biology · 2013Review
- Suramin decreases injury and improves regeneration of ethanol-induced steatotic partial liver grafts.The Journal of pharmacology and experimental therapeutics · 2013Article
- Nitric oxide is a mediator of antiproliferative effects induced by proinflammatory cytokines on pancreatic beta cells.Mediators of inflammation · 2013Article
- Effect of PRX-1 Downregulation in the Type 1 Diabetes Microenvironment.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2012Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pro-inflammatory cytokines are implicated as the main mediators of beta-cell death during type 1 diabetes but the exact mechanisms remain unknown. This study examined the effects of interleukin-1beta (IL-1beta), interferon-gamma (IFNgamma) and tumour necrosis factor alpha (TNFalpha) on a rat insulinoma cell line (RIN-r) in order to identify the core mechanism of cytokine-induced beta-cell death. Treatment of cells with a combination of IL-1beta and IFNgamma (IL-1beta/IFNgamma)induced apoptotic cell death. TNFalpha neither induced beta-cell death nor did it potentiate the effects of IL-1beta, IFNgamma or IL-1beta/IFNgamma . The cytotoxic effect of IL-1beta/IFNgamma was associated with the expression of inducible nitric oxide synthase (iNOS) and production of nitric oxide. Adenoviral-mediated expression of iNOS (AdiNOS) alone was sufficient to induce caspase activity and apoptosis. The broad range caspase inhibitor, Boc-D-fmk, blocked IL-1beta/IFNgamma -induced caspase activity, but not nitric oxide production nor cell death. However, pre-treatment with L-NIO, a NOS inhibitor, prevented nitric oxide production, caspase activity and reduced apoptosis. IL-1beta/IFNgamma -induced apoptosis was accompanied by loss of mitochondrial membrane potential, release of cytochrome c and cleavage of pro-caspase-9, -7 and -3. Transduction of cells with Ad-Bcl-X(L) blocked both iNOS and cytokine-mediated mitochondrial changes and subsequent apoptosis, downstream of nitric oxide. We conclude that cytokine-induced nitric oxide production is both essential and sufficient for caspase activation and beta-cell death, and have identified Bcl-X(L) as a potential target to combat beta-cell apoptosis.
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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 OpenQuestion graph.