The DOI matches its Crossref record, with a small difference in title or year; 32 of the 32 references it cites were found in a registry or an index.
Reactive Oxygen Species from Mitochondria Induce Cyclooxygenase-2 Gene Expression in Human Mesangial Cells
Open accessAbstract
Hyperglycemia increases the production of reactive oxygen species (ROS) from the mitochondrial electron transport chain in bovine endothelial cells. Because several studies have postulated a role for prostaglandins (PGs) in the glomerular hyperfiltration seen in early diabetes, we evaluated the effect of mitochondrial ROS on expression of the inducible isoform of cyclooxygenase (COX-2) in cultured human mesangial cells (HMCs). We first confirmed that incubation of HMC with 30 mmol/l glucose significantly increased COX-2 mRNA but not COX-1 mRNA, compared with 5.6 mmol/l glucose. Similarly, incubation of HMCs with 30 mmol/l glucose significantly increased mitochondrial membrane potential, intracellular ROS production, COX-2 protein expression, and PGE2 synthesis, and these events were completely suppressed by thenoyltrifluoroacetone or carbonyl cyanide m-chlorophenylhydrazone, inhibitors of mitochondrial metabolism, or by overexpression of uncoupling protein-1 or manganese superoxide dismutase. Furthermore, increased expression of COX-2 mRNA and protein was confirmed in glomeruli of streptozotocin-induced diabetic mice. In addition, hyperglycemia induced activation of the COX-2 gene promoter, which was completely abrogated by mutation of two nuclear factor κB (NF-κB) binding sites in the promoter region. Our results suggest that hyperglycemia increases mitochondrial ROS production, resulting in NF-κB activation, COX-2 mRNA induction, COX-2 protein production, and PGE2 synthesis. This chain of events might contribute to the pathogenesis of diabetic nephropathy.
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“Nox2-derived ROS [185] and matrix mtROS [186] were suggested to induce COX. However, this suggestion was based exclusively on data obtained with diphenyl iodinium (DPI), a general flavoprotein inhibitor with various side effects and with lack of specificity (see Section 7). Therefore, the findings are not fully conclusive.”
From Functions of ROS in Macrophages and Antimicrobial Immunity (2021) · cites this paper as [186]
In the citing paper
“This was suppressed by reduction in membrane potential by chemical inhibition or by UCP1 overexpression, but, curiously, also suppressed by MnSOD, which should actually increase H2O2 production from superoxide.”
From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [165]
In the citing paper
“High glucose also reportedly increased H2O2 production by dichlorodihydrofluorescein fluorescence in human mesangial cells (165).”
From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [165]
In the citing paper
“This was suppressed by reduction in membrane potential by chemical inhibition or by UCP1 overexpression, but, curiously, also suppressed by MnSOD, which should actually increase H2O2 production from superoxide.”
From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [165]
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Metadata
- Authors
- Kiritoshi, S., Nishikawa, T., Sonoda, K., Kukidome, D., Senokuchi, T., Matsuo, T., Matsumura, T., Tokunaga, H., Brownlee, M., & Araki, E.
- Affiliations
- Kumamoto University (JP)
- Albert Einstein College of Medicine (US)
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2003-10-01
- Volume
- 52
- Issue
- 10
- Pages
- 2570-2577
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2468150319
- Cited by
- 345
- References
- 31
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 7 · 2023: 8 · 2022: 18 · 2021: 12 · 2020: 8 · 2019: 12 · 2018: 10 · 2017: 11 · 2016: 15 · 2015: 14 · 2014: 20 · 2013: 16 · 2012: 26
- FWCI
- 9.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Kanae Foundation for the Promotion of Medical Science
- Japan Diabetes Foundation
- Japan Society for the Promotion of Science (14571100)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Inflammatory mediators and NSAID effects
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Keywords
- reactive oxygen species, mitochondrial reactive oxygen species, cyclooxygenase-2, mesangial cells, hyperglycemia, NF-κB, prostaglandin E2, diabetic nephropathy, glomerular hyperfiltration, UCP1, manganese superoxide dismutase, COX-2 promoter, streptozotocin-induced diabetes
- MeSH terms
- Uncoupling Protein 1, Animals, Carbonyl Cyanide m-Chlorophenyl Hydrazone, Carrier Proteins, Cells, Cultured, Chelating Agents, Diabetes Mellitus, Experimental, Diabetic Neuropathies, Dose-Response Relationship, Drug, Glomerular Mesangium, Glucose, Humans, Ion Channels, Ionophores, Isoenzymes, Membrane Proteins, Mitochondria, Promoter Regions, Genetic, Prostaglandin-Endoperoxide Synthases, RNA, Messenger, Superoxide Dismutase, Thenoyltrifluoroacetone, Gene Expression, Reactive Oxygen Species, Mitochondrial Proteins, Mice, Cyclooxygenase 1, Cyclooxygenase 2
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