ArticleAmerican journal of respiratory cell and molecular biology2008
Transcription factors sp1 and sp3 regulate expression of human extracellular superoxide dismutase in lung fibroblasts.
Article in American journal of respiratory cell and molecular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 35 citations in OpenAlex.
- Extracellular Superoxide Dismutase in Acute Respiratory Distress Syndrome: Pathogenic Mechanisms and Therapeutic Implications.Antioxidants (Basel, Switzerland) · 2026Review
- Combining sorafenib with spermine and sphingosine synergistically enhances anticancer efficacy by modulating metabolic pathways and gut microbiome in hepatocellular carcinoma.International journal of biological sciences · 2026Article
- Influence ofGenes · 2021Article
- Bioreactor-Controlled Physoxia Regulates TGF-β Signaling to Alter Extracellular Matrix Synthesis by Human Chondrocytes.International journal of molecular sciences · 2019Article
- Semen Exosomes Promote Transcriptional Silencing of HIV-1 by Disrupting NF-κB/Sp1/Tat Circuitry.Journal of virology · 2018Article
- Tumor necrosis factor-α decreases EC-SOD expression through DNA methylation.Journal of clinical biochemistry and nutrition · 2017Article
- Propiece IL-1α facilitates the growth of acute T-lymphocytic leukemia cells through the activation of NF-κB and SP1.Oncotarget · 2017Article
- Trefoil factor family 2 expression inhibits gastric cancer cell growth and invasion in vitro via interactions with the transcription factor Sp3.International journal of molecular medicine · 2016Article
- Histone deacetylation contributes to low extracellular superoxide dismutase expression in human idiopathic pulmonary arterial hypertension.American journal of physiology. Lung cellular and molecular physiology · 2016Article
- Exendin-4 promotes extracellular-superoxide dismutase expression in A549 cells through DNA demethylation.Journal of clinical biochemistry and nutrition · 2016Article
- Regulation of Oxidative Stress in Pulmonary Artery Endothelium. Modulation of Extracellular Superoxide Dismutase and NOX4 Expression Using Histone Deacetylase Class I Inhibitors.American journal of respiratory cell and molecular biology · 2015Article
- Genetic and epigenetic inactivation of extracellular superoxide dismutase promotes an invasive phenotype in human lung cancer by disrupting ECM homeostasis.Molecular cancer research : MCR · 2012Article
- Histone acetylation regulates the cell-specific and interferon-γ-inducible expression of extracellular superoxide dismutase in human pulmonary arteries.American journal of respiratory cell and molecular biology · 2011Article
- The effects of aging on pulmonary oxidative damage, protein nitration, and extracellular superoxide dismutase down-regulation during systemic inflammation.Free radical biology & medicine · 2011Article
- Glutamine protects against apoptosis via downregulation of Sp3 in intestinal epithelial cells.American journal of physiology. Gastrointestinal and liver physiology · 2010Article
- Genomic features of the human dopamine transporter gene and its potential epigenetic States: implications for phenotypic diversity.PloS one · 2010Article
- CpG methylation attenuates Sp1 and Sp3 binding to the human extracellular superoxide dismutase promoter and regulates its cell-specific expression.Free radical biology & medicine · 2010Article
- Extracellular SOD and VEGF are increased in vitreous bodies from proliferative diabetic retinopathy patients.Molecular vision · 2009Article
- Regulation of superoxide dismutase genes: implications in disease.Free radical biology & medicine · 2009Review
- Superoxide dismutase 3, extracellular (SOD3) variants and lung function.Physiological genomics · 2009Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The molecular mechanisms that govern the transcription of human extracellular superoxide dismutase (EC-SOD), the major extracellular antioxidant enzyme, are largely unknown. To elucidate the mechanisms involved in human EC-SOD gene regulation and expression, we localized multiple transcription start sites to a finite region located 3.9 kb upstream of the ATG initiation codon. Within this segment, we subcloned a 2.7-kb fragment upstream of a luciferase reporter gene; the resulting construct exhibited strong in vivo promoter activity in two lung-derived cell lines. Deletion analysis of the EC-SOD 5'-flanking sequences identified a minimal 0.3-kb region that had strong basal promoter activity. Computer sequence analysis revealed a putative Sp1-like binding site within the EC-SOD proximal promoter region that lacked a TATA-box and showed a high frequency of GC nucleotides. Binding of Sp1 and Sp3 transcription factors to the EC-SOD promoter was confirmed by DNase I footprint analysis, electophoretic mobility shift assay, and competition and supershift assays. Cotransfection of the EC-SOD promoter-luciferase reporter constructs with plasmids encoding Sp1 and Sp3 into Sp-deficient insect SL2 cells showed strong activation of luciferase gene expression. The occupancy of the EC-SOD promoter by Sp1/Sp3 and RNA polymerase II in vivo was determined by chromatin immunoprecipitation assay and correlated well with levels of EC-SOD expression in lung epithelial cells (A549) and pulmonary fibroblasts (MRC5). Collectively, our results demonstrate the important role Sp1 and Sp3 plays in regulating the expression of human EC-SOD in the lung.
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