Inhibition of myeloperoxidase decreases vascular oxidative stress and increases vasodilatation in sickle cell disease mice
| Autor: | Xigang Jing, Kirkwood A. Pritchard, Dorothee Weihrauch, Keith T. Oldham, Deron W. Jones, Hao Xu, Hao Zhang, Yang Shi, David M. Gourlay, Cheryl A. Hillery |
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| Rok vydání: | 2013 |
| Předmět: |
Male
congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty Vasodilation Anemia Sickle Cell medicine.disease_cause Biochemistry Nitric oxide Mice chemistry.chemical_compound Endocrinology hemic and lymphatic diseases Internal medicine medicine Animals Humans cardiovascular diseases Enzyme Inhibitors L-Selectin Research Articles Peroxidase Liver injury Dose-Response Relationship Drug biology Endothelial Cells Cell Biology Malondialdehyde medicine.disease Hypochlorous Acid Oxidative Stress Liver Solubility chemistry Alanine transaminase Myeloperoxidase Immunology biology.protein Blood Vessels Female L-selectin Oligopeptides Oxidative stress |
| Zdroj: | Journal of Lipid Research. 54:3009-3015 |
| ISSN: | 0022-2275 |
| Popis: | Activated leukocytes and polymorphonuclear neutrophils (PMN) release myeloperoxidase (MPO), which binds to endothelial cells (EC), is translocated, and generates oxidants that scavenge nitric oxide (NO) and impair EC function. To determine whether MPO impairs EC function in sickle cell disease (SCD), control (AA) and SCD mice were treated with N-acetyl-lysyltyrosylcysteine-amide (KYC). SCD humans and mice have high plasma MPO and soluble L-selectin (sL-selectin). KYC had no effect on MPO but decreased plasma sL-selectin and malondialdehyde in SCD mice. MPO and 3-chlorotyrosine (3-ClTyr) were increased in SCD aortas. KYC decreased MPO and 3-ClTyr in SCD aortas to the levels in AA aortas. Vasodilatation in SCD mice was impaired. KYC increased vasodilatation in SCD mice more than 2-fold, to ∼60% of levels in AA mice. KYC inhibited MPO-dependent 3-ClTyr formation in EC proteins. SCD mice had high plasma alanine transaminase (ALT), which tended to decrease in KYC-treated SCD mice (P = 0.07). KYC increased MPO and XO/XDH and decreased 3-ClTyr and 3-nitrotyrosine (3-NO2Tyr) in SCD livers. These data support the hypothesis that SCD increases release of MPO, which generates oxidants that impair EC function and injure livers. Inhibiting MPO is an effective strategy for decreasing oxidative stress and liver injury and restoring EC function in SCD. |
| Databáze: | OpenAIRE |
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