The thiazolidinedione drug troglitazone up-regulates nitric oxide synthase expression in vascular endothelial cells
Abstract
Endothelial dysfunction is a phenomenon often observed in diabetic patients, which is a cause for vascular complications of diabetes mellitus. Endothelium-derived nitric oxide (NO) is responsible for vasodilatation, and NO-dependent vasodilatation is diminished in diabetic patients. In the present study, we evaluated the effects of thiazolidinediones (TZDs), antidiabetic drugs known to improve insulin resistance and to have vasodilating properties, on endothelial NO synthase (eNOS) expression in cultured vascular endothelial cells. Human umbilical vein endothelial cells were treated with the TZDs troglitazone and pioglitazone, or the peroxisome proliferator-activated receptor (PPAR) gamma activator 15-deoxy-Delta(12,14)-prostaglandin J(2) (15-dPGJ2). The expression of eNOS protein and its mRNA was determined by Western and Northern blot analyses, respectively. The effect of alpha-tocopherol that possesses structural similarity to troglitazone was also examined. Troglitazone up-regulated eNOS protein and its mRNA levels, whereas pioglitazone and 15-dPGJ2 failed to increase their levels. By contrast, alpha-tocopherol also increased in eNOS protein and mRNA. These results suggest that troglitazone up-regulates eNOS expression probably through its 6-hydroxychromanes structure but not activating PPARgamma.
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Vitamin E inhibits the protein kinase C pathway, NF-kappa B, and IkappaB degradation, all activated by oxidized low-density lipoprotein.
“Vitamin E inhibits the protein kinase C pathway, NF-kappa B, and IkappaB degradation, all activated by oxidized low-density lipoprotein (LDL) (Goya et al. 2006).”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Goya et al. 2006
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“[188–191].”
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- Authors
- Goya, K., Sumitani, S., Otsuki, M., Xu, X., Yamamoto, H., Kurebayashi, S., Saito, H., Kouhara, H., & Kasayama, S.
- Affiliations
- The University of Osaka (JP)
- Corresponding author
- Kasayama, Soji
- Venue
- Journal of Diabetes and its Complications
- Publisher
- Elsevier BV
- Published
- 2006-09
- Volume
- 20
- Issue
- 5
- Pages
- 336-342
- ISSN
- 0891-6632 (ISSN-L)
- 1056-8727
- OpenAlex
- W2002935731
- Cited by
- 43
- References
- 57
- Citations by year
- 2026: 1 · 2023: 2 · 2022: 1 · 2021: 1 · 2019: 2 · 2018: 1 · 2016: 2 · 2015: 1 · 2014: 3 · 2013: 2 · 2012: 5
- FWCI
- 3.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Diabetes and its Complications (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Paraoxonase enzyme and polymorphisms
- Keywords
- troglitazone, pioglitazone, thiazolidinediones, endothelial nitric oxide synthase, eNOS expression, endothelial dysfunction, diabetes mellitus, vascular endothelial cells, 15-deoxy-Δ12,14-prostaglandin J2, alpha-tocopherol, PPARγ, vasodilation
- MeSH terms
- Troglitazone, Analysis of Variance, Cells, Cultured, Chromans, Humans, Hypoglycemic Agents, RNA, Messenger, Umbilical Veins, Vasodilation, Prostaglandin D2, Up-Regulation, alpha-Tocopherol, Endothelial Cells, Thiazolidinediones, Nitric Oxide Synthase Type III
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