ArticleToxicological sciences : an official journal of the Society of Toxicology2013
Hypoxia-response element (HRE)-directed transcriptional regulation of the rat lysyl oxidase gene in response to cobalt and cadmium.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
- Enzymatic and non-enzymatic oxidation of fibrillar collagen.Redox report : communications in free radical research · 2026Review
- Therapeutic Targets for Hepatic Fibrosis Driven by Hypoxia-Mediated Hepatic Stellate Cell Activation.Biomolecules · 2026Review
- Ultrasound priming gated by solid tumor hallmarks to guide CAR-T therapy.Science advances · 2026Article
- Envirotune-CAR-T: a hypoxia-responsive and glutamine-enhanced CAR-T cell therapy for overcoming tumor microenvironment-mediated suppression.Journal for immunotherapy of cancer · 2025Article
- In Vitro Sonodynamic Therapy Using a High Throughput 3D Glioblastoma Spheroid Model with 5-ALA and TMZ Sonosensitizers.Advanced healthcare materials · 2024Article
- Glycolytic enzymes in non-glycolytic web: functional analysis of the key players.Cell biochemistry and biophysics · 2024Review
- Crosstalk between DNA methylation and hypoxia in acute myeloid leukaemia.Clinical epigenetics · 2023Review
- C4orf47 contributes to the dormancy of pancreatic cancer under hypoxic conditions.Journal of Cancer · 2023Article
- Hypoxia Affects the Antioxidant Activity of Glutaredoxin 3 inAntioxidants (Basel, Switzerland) · 2022Article
- Renal hypoxia-HIF-PHD-EPO signaling in transition metal nephrotoxicity: friend or foe?Archives of toxicology · 2022Review
- Regulators of collagen crosslinking in developing and adult tendons.European cells & materials · 2022Review
- Hypoxia-inducible factor 1α induces osteo/odontoblast differentiation of human dental pulp stem cells via Wnt/β-catenin transcriptional cofactor BCL9.Scientific reports · 2022Article
- Conditioned CAR-T cells by hypoxia-inducible transcription amplification (HiTA) system significantly enhances systemic safety and retains antitumor efficacy.Journal for immunotherapy of cancer · 2021Article
- Synthetic promoters to induce immune-effectors into the tumor microenvironment.Communications biology · 2021Article
- Molecular Insights Into Lysyl Oxidases in Cartilage Regeneration and Rejuvenation.Frontiers in bioengineering and biotechnology · 2020Review
- Genome-Wide Interrogation of Human Cancers Identifies EGLN1 Dependency in Clear Cell Ovarian Cancers.Cancer research · 2019Article
- Intrauterine Exposure to Cadmium Reduces HIF-1 DNA-Binding Ability in Rat Fetal Kidneys.Toxics · 2018Article
- Cadmium Exposure Inhibits Branching Morphogenesis and Causes Alterations Consistent With HIF-1α Inhibition in Human Primary Breast Organoids.Toxicological sciences : an official journal of the Society of Toxicology · 2018Article
- Lysyl Oxidase and the Tumor Microenvironment.International journal of molecular sciences · 2016Review
- Hypoxia-inducible factor-2 alpha promotes the proliferation of human placenta-derived mesenchymal stem cells through the MAPK/ERK signaling pathway.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Lysyl oxidase (LO) catalyzes crosslink of collagen, elastin, and histone H1, stabilizing the extracellular matrix and cell nucleus. This enzyme displays dual functions for tumorigenesis, i.e., as a tumor suppressor inactivating the ras oncogene and as a tumor promoter enhancing malignant cell metastasis. To elucidate LO transcriptional regulation, we have cloned the 804 base pair region upstream of the translation start site (ATG) of the rat LO gene with the maximal promoter activity. Computer analysis indicated that at least four hypoxia-response element (HRE) consensuses (5'-ACGTG-3') exist in the cloned LO promoter. Treatment of rat lung fibroblasts (RFL6) with CoCl2 (Co, 10-100 μM), a chemical hypoxia reagent, enhanced LO mRNA expression and promoter activities. Overexpression of LO was associated with upregulation of hypoxia-inducible factor (HIF)-1α at mRNA levels in cobalt (Co)-treated cells. Thus, LO is a hypoxia-responsive gene. Dominant negative-HIF-1α inhibited LO promoter activities stimulated by Co. Electrophoretic mobility shift, oligonucleotide competition, and in vitro translated HIF-1α binding assays indicated that only one HRE mapped at -387/-383 relative to ATG was functionally active among four consensuses. Site-directed mutation of this HRE significantly diminished the Co-induced and LO promoter-directed expression of the reporter gene. Cadmium (Cd), an inducer of reactive oxygen species, inhibited HIF-1α mRNA expression and HIF-1α binding to the LO gene in Co-treated cells as revealed by RT-PCR and ChIP assays, respectively. Thus, modulation of the HRE activity by Co and Cd plays a critical role in LO gene transactivation.
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