ArticleThe Journal of biological chemistry2009
Reactive oxygen species-generating mitochondrial DNA mutation up-regulates hypoxia-inducible factor-1alpha gene transcription via phosphatidylinositol 3-kinase-Akt/protein kinase C/histone deacetylase pathway.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 2 of them syntheses that pooled it.
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Who cites it
82 citing papers in PubMed, 2 syntheses or guidelines pooled it, 146 citations in OpenAlex.
- Aberrant Energy Metabolism in Tumors and Potential Therapeutic Targets.Genes, chromosomes & cancer · 2024Pooled it
- Molecular oncology focus - is carcinogenesis a 'mitochondriopathy'?Journal of biomedical science · 2010Pooled it
- CRACD loss drives hypoxia-induced immune escape in gastric cancer.Nature communications · 2026Article
- Investigating hypoxia-inducible factor signaling in cancer: Mechanisms, clinical implications, targeted therapeutic strategies, and resistance.Cancer pathogenesis and therapy · 2026Review
- Decoding macrophage heterogeneity in the pulmonary fibrosis lung cancer transition.Frontiers in immunology · 2026Review
- Role of hypoxia-inducible factor - 1 alpha on the progression of cervical intraepithelial neoplasia and cervical cancer: a narrative review.Frontiers in oncology · 2026Review
- Metabolic Signaling in the Tumor Microenvironment.Cancers · 2025Review
- EGCG activates Keap1/P62/Nrf2 pathway, inhibits iron deposition and apoptosis in rats with cerebral hemorrhage.Scientific reports · 2024Article
- 3D biological scaffold delivers Bergenin to reduce neuroinflammation in rats with cerebral hemorrhage.Journal of translational medicine · 2024Article
- Controlling Pericellular Oxygen Tension in Cell Culture Reveals Distinct Breast Cancer Responses to Low Oxygen Tensions.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- An antioxidant response element regulates the HIF1α axis in breast cancer cells.Free radical biology & medicine · 2023Article
- Hypoxia-Inducible Factor 1 and Mitochondria: An Intimate Connection.Biomolecules · 2022Review
- The effect of HIF on metabolism and immunity.Nature reviews. Nephrology · 2022Review
- The CD146-HIF-1α axis regulates epithelial cell migration and alveolar maturation in a mouse model of bronchopulmonary dysplasia.Laboratory investigation; a journal of technical methods and pathology · 2022Article
- Epigallocatechin Gallate Protects against Hypoxia-Induced Inflammation in Microglia via NF-κB Suppression and Nrf-2/HO-1 Activation.International journal of molecular sciences · 2022Article
- Roxadustat: Not just for anemia.Frontiers in pharmacology · 2022Review
- LRPPRC regulates metastasis and glycolysis by modulating autophagy and the ROS/HIF1-α pathway in retinoblastoma.Molecular therapy oncolytics · 2021Article
- Macrophage Motility in Wound Healing Is Regulated by HIF-1α via S1P Signaling.International journal of molecular sciences · 2021Review
- An Overview of the Recent Development of Anticancer Agents Targeting the HIF-1 Transcription Factor.Cancers · 2021Review
- Antitumor effects of low-dose tipifarnib on the mTOR signaling pathway and reactive oxygen species production in HIF-1α-expressing gastric cancer cells.FEBS open bio · 2021Article
22 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lewis lung carcinoma-derived high metastatic A11 cells constitutively overexpress hypoxia-inducible factor (HIF)-1alpha mRNA compared with low metastatic P29 cells. Because A11 cells exclusively possess a G13997A mutation in the mitochondrial NADH dehydrogenase subunit 6 (ND6) gene, we addressed here a causal relationship between the ND6 mutation and the activation of HIF-1alpha transcription, and we investigated the potential mechanism. Using trans-mitochondrial cybrids between A11 and P29 cells, we found that the ND6 mutation was directly involved in HIF-1alpha mRNA overexpression. Stimulation of HIF-1alpha transcription by the ND6 mutation was mediated by overproduction of reactive oxygen species (ROS) and subsequent activation of phosphatidylinositol 3-kinase (PI3K)-Akt and protein kinase C (PKC) signaling pathways. The up-regulation of HIF-1alpha transcription was abolished by mithramycin A, an Sp1 inhibitor, but luciferase reporter and chromatin immunoprecipitation assays indicated that Sp1 was necessary but not sufficient for HIF-1alpha mRNA overexpression in A11 cells. On the other hand, trichostatin A, a histone deacetylase (HDAC) inhibitor, markedly suppressed HIF-1alpha transcription in A11 cells. In accordance with this, HDAC activity was high in A11 cells but low in P29 cells and in A11 cells treated with the ROS scavenger ebselene, the PI3K inhibitor LY294002, and the PKC inhibitor Ro31-8220. These results suggest that the ROS-generating ND6 mutation increases HIF-1alpha transcription via the PI3K-Akt/PKC/HDAC pathway, leading to HIF-1alpha protein accumulation in hypoxic tumor cells.
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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.