Cellular Carbonyl Stress Enhances the Expression of Plasminogen Activator Inhibitor-1 in Rat White Adipocytes via Reactive Oxygen Species-dependent Pathway
| Autor: | Yoko Uchida, Ken-ichi Ohba, Yoshiro Maru, Kaoru Irie, Takamura Muraki, Toshimasa Yoshioka |
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| Rok vydání: | 2004 |
| Předmět: |
Glycation End Products
Advanced Male medicine.medical_specialty Rats Inbred OLETF Adipose tissue medicine.disease_cause Biochemistry Antioxidants Lipid peroxidation chemistry.chemical_compound Pyrrolidine dithiocarbamate Glycation Internal medicine Plasminogen Activator Inhibitor 1 Adipocytes medicine Animals RNA Messenger Buthionine Sulfoximine Molecular Biology Cells Cultured chemistry.chemical_classification Aldehydes Reactive oxygen species NF-kappa B Deoxyguanosine Free Radical Scavengers Cell Biology Acetylcysteine Rats Up-Regulation Oxidative Stress Endocrinology Diabetes Mellitus Type 2 chemistry 8-Hydroxy-2'-Deoxyguanosine Plasminogen activator inhibitor-1 Lipid Peroxidation Reactive Oxygen Species Plasminogen activator Diabetic Angiopathies Oxidative stress |
| Zdroj: | Journal of Biological Chemistry. 279:4075-4083 |
| ISSN: | 0021-9258 |
| Popis: | Carbonyl stress is one of the important mechanisms of tissue damage in vascular complications of diabetes. In the present study, we observed that the plasminogen activator inhibitor-1 (PAI-1) levels in serum and its gene expression in adipose tissue were up-regulated in aged OLETF rats, model animals of obese type 2 diabetes. To study the mechanism of PAI-1 up-regulation, we examined the effect of advanced glycation end products (AGEs) and the product of lipid peroxidation (4-hydroxy-2-nonenal (HNE)), both of which are endogenously generated under carbonyl stress. Stimulation of primary white adipocytes by either AGE or HNE resulted in the elevation of PAI-1 in culture medium and at mRNA levels. The up-regulation of PAI-1 was also observed by incubating the cells in high glucose medium (30 mm, 48 h). The stimulatory effects by AGE or high glucose were inhibited by antioxidant, pyrrolidine dithiocarbamate, and reactive oxygen scavenger, probucol, suggesting a pivotal role of oxidative stress in white adipocytes. We also found that the effect by HNE was inhibited by antioxidant, N-acetylcysteine and that a specific inhibitor of glutathione biosynthesis, l-buthionine-S,R-sulfoximine, augmented the effect of subthreshold effect of HNE. Bioimaging of reactive oxygen species (ROS) by a fluorescent indicator, 6-carboxy-2',7'-dichlorodihydrofluorescein diacetate, revealed ROS production in white adipocytes treated with AGE or HNE. These results suggest that cellular carbonyl stress induced by AGEs or HNE may stimulate PAI-1 synthesis in and release from adipose tissues through ROS formation. |
| Databáze: | OpenAIRE |
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