ArticleThe Journal of biological chemistry2011
Cellular iron depletion stimulates the JNK and p38 MAPK signaling transduction pathways, dissociation of ASK1-thioredoxin, and activation of ASK1.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 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
47 citing papers in PubMed, 110 citations in OpenAlex.
- Role of vascular smooth muscle phenotypic transformation induced by histone modifications in the development of abdominal aortic aneurysms.Clinical epigenetics · 2025Review
- Metal Ion Signaling in Biomedicine.Chemical reviews · 2025Review
- PGK1 Is Involved in the HIF-1 Signaling Pathway as a Hub Gene for Ferroptosis After Traumatic Brain Injury.Molecular neurobiology · 2025Article
- Macrophage heterogeneity in liver fibrosis.Frontiers in immunology · 2025Review
- Apoptosis signal-regulating kinase 1 (Frontiers in cellular neuroscience · 2024Article
- Chelators as Antineuroblastomas Agents.Physiological research · 2023Article
- ASK1 Regulates Bleomycin-induced Pulmonary Fibrosis.American journal of respiratory cell and molecular biology · 2022Article
- Functional Roles of JNK and p38 MAPK Signaling in Nasopharyngeal Carcinoma.International journal of molecular sciences · 2022Review
- Deferoxamine Inhibits Acute Lymphoblastic Leukemia Progression through Repression of ROS/HIF-1Journal of oncology · 2022Article
- Article
- Reversing oncogenic transformation with iron chelation.Oncotarget · 2021Review
- Bioinformatics Analysis Identifies Potential Ferroptosis Key Genes in the Pathogenesis of Intracerebral Hemorrhage.Frontiers in neuroscience · 2021Article
- The Writers, Readers, and Erasers in Redox Regulation of GAPDH.Antioxidants (Basel, Switzerland) · 2020Review
- Lipocalin-2 mediates HIV-1 induced neuronal injury and behavioral deficits by overriding CCR5-dependent protection.Brain, behavior, and immunity · 2020Article
- Reactivation of Epstein-Barr Virus by HIF-1α Requires p53.Journal of virology · 2020Article
- Dp44mT, an iron chelator, suppresses growth and induces apoptosis via RORA-mediated NDRG2-IL6/JAK2/STAT3 signaling in glioma.Cellular oncology (Dordrecht, Netherlands) · 2020Article
- Air pollutants disrupt iron homeostasis to impact oxidant generation, biological effects, and tissue injury.Free radical biology & medicine · 2020Review
- Management of Iron Overload in Resource Poor Nations: A Systematic Review of Phlebotomy and Natural Chelators.Journal of toxicology · 2020Review
- From Iron Chelation to Overload as a Therapeutic Strategy to Induce Ferroptosis in Leukemic Cells.Frontiers in oncology · 2020Review
- Iron and leukemia: new insights for future treatments.Journal of experimental & clinical cancer research : CR · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The role of signaling pathways in the regulation of cellular iron metabolism is becoming increasingly recognized. Iron chelation is used for the treatment of iron overload but also as a potential strategy for cancer therapy, because iron depletion results in cell cycle arrest and apoptosis. This study examined potential signaling pathways affected by iron depletion induced by desferrioxamine (DFO) or di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT). Both chelators affected multiple molecules in the mitogen-activated protein kinase (MAPK) pathway, including a number of dual specificity phosphatases that directly de-phosphorylate MAPKs. Examination of the phosphorylation of major MAPKs revealed that DFO and Dp44mT markedly increased phosphorylation of stress-activated protein kinases, JNK and p38, without significantly affecting the extracellular signal-regulated kinase (ERK). Redox-inactive DFO-iron complexes did not affect phosphorylation of JNK or p38, whereas the redox-active Dp44mT-iron complex significantly increased the phosphorylation of these kinases similarly to Dp44mT alone. Iron or N-acetylcysteine supplementation reversed Dp44mT-induced up-regulation of phospho-JNK, but only iron was able to reverse the effect of DFO on JNK. Both iron chelators significantly reduced ASK1-thioredoxin complex formation, resulting in the increased phosphorylation of ASK1, which activates the JNK and p38 pathways. Thus, dissociation of ASK1 could serve as an important signal for the phosphorylation of JNK and p38 activation observed after iron chelation. Phosphorylation of JNK and p38 likely play an important role in mediating the cell cycle arrest and apoptosis induced by iron depletion.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.