Thioredoxin reductase regulates the induction of haem oxygenase-1 expression in aortic endothelial cells
| Autor: | Isis K. Mullarky, Yu-Zhang Cao, Lorraine M. Sordillo, Wendy L. Trigona |
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| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
Leukotrienes
Lipid Peroxides Antioxidant Thioredoxin-Disulfide Reductase medicine.medical_treatment Thioredoxin reductase Stimulation Apoptosis Biology Biochemistry chemistry.chemical_compound Selenium medicine Animals Selenoproteins Molecular Biology Aorta Cells Cultured chemistry.chemical_classification Endothelial Cells Cell Biology Glutathione Cell biology Oxidative Stress chemistry Enzyme Induction Cattle RNA Interference Selenoprotein Thioredoxin Reactive Oxygen Species Intracellular Heme Oxygenase-1 Research Article |
| Popis: | Certain selenoproteins such as GPX-1 (glutathione peroxidase-1) and TrxR1 (thioredoxin reductase-1) possess important antioxidant defence functions in vascular endothelial cells. Reduced selenoprotein activity during dietary selenium (Se) deficiency can result in a compensatory increase of other non-Se-dependent antioxidants, such as HO-1 (haem oxygenase-1) that may help to counteract the damaging effects of oxidant stress. However, the role of individual selenoproteins in regulating vascular-derived protective gene responses such as HO-1 is less understood. Using an oxidant stress model based on Se deficiency in BAECs (bovine aortic endothelial cells), we sought to determine whether TrxR1 activity may contribute to the differential regulation of HO-1 expression as a function of altered redox environment. Se-sufficient BAECs up-regulated HO-1 expression following stimulation with the pro-oxidant, 15-HPETE (15-hydroperoxyeicosatetraenoic acid), and levels of this antioxidant inversely correlated with EC apoptosis. While Se-deficient BAECs exhibited higher basal levels of HO-1, it was not up-regulated upon 15-HPETE treatment, which resulted in significantly higher levels of pro-apoptotic markers. Subsequent results showed that HO-1 induction depended on the activity of TrxR1, as proved with chemical inhibitor studies and direct inhibition with TrxR1 siRNA. Finally, restoring intracellular levels of the reduced substrate Trx (thioredoxin) in Sedeficient BAECs was sufficient to increase HO-1 activation following 15-HPETE stimulation. These data provide evidence for the involvement of the Trx/TrxR system, in the regulation of HO-1 expression in BAECs during pro-oxidant challenge. |
| Databáze: | OpenAIRE |
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