ArticleProceedings of the National Academy of Sciences of the United States of America2002
Uncoupling protein 2 plays an important role in nitric oxide production of lipopolysaccharide-stimulated macrophages.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 136 citations in OpenAlex.
- Reactive Oxygen and Nitrogen Species on Monocyte and Macrophage Biology.Antioxidants (Basel, Switzerland) · 2026Review
- Mito-Genipin, a Novel Mitochondria-Targeted Genipin Derivative Modulates Oxidative Stress and Inflammation in Macrophages.Antioxidants (Basel, Switzerland) · 2025Article
- Extract of camellia seed cake ameliorates glycolipid metabolism disorder in mice through inhibiting ACOX1 activity.Food chemistry: X · 2025Article
- Mitochondrial network adaptations of microglia reveal sex-specific stress response after injury and UCP2 knockout.iScience · 2023Article
- Cellular heterogeneity and plasticity during NAFLD progression.Frontiers in molecular biosciences · 2023Review
- Transcriptional differences between coronavirus disease 2019 and bacterial sepsis.Virology journal · 2022Article
- Photobiomodulation therapy preconditioning modifies nitric oxide pathway and oxidative stress in human-induced pluripotent stem cell-derived ventricular cardiomyocytes treated with doxorubicin.Lasers in medical science · 2022Article
- Mitochondrial Uncoupling Proteins (UCPs) as Key Modulators of ROS Homeostasis: A Crosstalk between Diabesity and Male Infertility?Antioxidants (Basel, Switzerland) · 2021Review
- Mitochondria as a Cellular Hub in Infection and Inflammation.International journal of molecular sciences · 2021Review
- BAM15, a Mitochondrial Uncoupling Agent, Attenuates Inflammation in the LPS Injection Mouse Model: An Adjunctive Anti-Inflammation on Macrophages and Hepatocytes.Journal of innate immunity · 2021Article
- Macrophage activation as an archetype of mitochondrial repurposing.Molecular aspects of medicine · 2020Review
- Cinnamic Aldehyde Inhibits Lipopolysaccharide-Induced Chondrocyte Inflammation and Reduces Cartilage Degeneration by Blocking the Nuclear Factor-Kappa B Signaling Pathway.Frontiers in pharmacology · 2020Article
- Uncoupling protein-2 regulates M1 macrophage infiltration of gingiva with periodontitis.Central-European journal of immunology · 2020Article
- Pivotal Role of Mitochondria in Macrophage Response to Bacterial Pathogens.Frontiers in immunology · 2019Review
- Down regulation of UCP2 expression in retinal pigment epithelium cells under oxidative stress: anInternational journal of ophthalmology · 2019Article
- Cytoprotective activity of mitochondrial uncoupling protein-2 in lung and spleen.FEBS open bio · 2018Article
- Overexpressed UCP2 regulates mitochondrial flashes and reverses lipopolysaccharide-induced cardiomyocytes injury.American journal of translational research · 2018Article
- Microglia antioxidant systems and redox signalling.British journal of pharmacology · 2017Review
- Effects of peroxisome proliferator activated receptors (PPAR)-γ and -α agonists on cochlear protection from oxidative stress.PloS one · 2017Article
- Uncoupling Protein 2: A Key Player and a Potential Therapeutic Target in Vascular Diseases.Oxidative medicine and cellular longevity · 2017Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The expression of uncoupling protein 2 (UCP2) was reduced in macrophages after stimulation with lipopolysaccharide (LPS). The physiological consequence and the regulatory mechanisms of the UCP2 down-regulation by LPS were investigated in a macrophage cell line, RAW264 cells. UCP2 overexpression in RAW264 cells transfected with eukaryotic expression vector containing ucp2 cDNA markedly reduced the production of intracellular reactive oxygen species. Furthermore, in the UCP2 transfectant, nitric oxide (NO) synthesis, inducible NO synthase (NOS II) protein, NOS II mRNA, and NOS II promoter activity were definitely decreased after LPS stimulation compared with those in parental RAW264 or RAW264 cells transfected with the vector alone. Reporter assays suggested that an enhancer element was located in the region of intron 2 of the UCP2 gene and that the UCP2 expression was down-regulated not by the 7.3-kb promoter region but by the 5' region of the UCP2 gene containing two introns. Deletion of intron 2 resulted in the low transcriptional activities and abolishment of the LPS-associated negative regulation. In addition, the mRNA expression of transfected UCP2 was suppressed in RAW264 cells transfected with expression vector containing UCP2 genomic DNA, but was markedly increased in cells transfected with the vector containing UCP2 intronless cDNA. These findings suggest that the LPS-stimulated signals suppress UCP2 expression by interrupting the function of intronic enhancer, leading to an up-regulation of intracellular reactive oxygen species, which activate the signal transduction cascade of NOS II expression, probably to ensure rapid and sufficient cellular responses to a microbial attack.
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