Monoamine oxidases are novel sources of cardiovascular oxidative stress in experimental diabetes
| Autor: | Danina Muntean, András Varró, Oana Duicu, Maria D. Dănilă, Adrian Sturza, Adrian Vaduva, Lavinia Noveanu |
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| Rok vydání: | 2015 |
| Předmět: |
Male
medicine.medical_specialty Physiology Gene Expression medicine.disease_cause Real-Time Polymerase Chain Reaction Streptozocin Diabetes Mellitus Experimental Physiology (medical) Diabetes mellitus Internal medicine Clorgyline medicine Animals Endothelial dysfunction Rats Wistar Monoamine Oxidase Aorta Pharmacology chemistry.chemical_classification Reactive oxygen species Myocardium Selegiline Oxidative deamination General Medicine medicine.disease Immunohistochemistry Oxidative Stress Monoamine neurotransmitter Endocrinology chemistry Cardiovascular Diseases Endothelium Vascular Reactive Oxygen Species Oxidative stress medicine.drug |
| Zdroj: | Canadian journal of physiology and pharmacology. 93(7) |
| ISSN: | 1205-7541 |
| Popis: | Diabetes mellitus (DM) is widely recognized as the most severe metabolic disease associated with increased cardiovascular morbidity and mortality. The generation of reactive oxygen species (ROS) is a major event causally linked to the development of cardiovascular complications throughout the evolution of DM. Recently, monoamine oxidases (MAOs) at the outer mitochondrial membrane, with 2 isoforms, MAO-A and MAO-B, have emerged as novel sources of constant hydrogen peroxide (H2O2) production in the cardiovascular system via the oxidative deamination of biogenic amines and neurotransmitters. Whether MAOs are mediators of endothelial dysfunction in DM is unknown, and so we studied this in a streptozotocin-induced rat model of diabetes. MAO expression (mRNA and protein) was increased in both arterial samples and hearts isolated from the diabetic animals. Also, H2O2 production (ferrous oxidation – xylenol orange assay) in aortic samples was significantly increased, together with an impairment of endothelium-dependent relaxation (organ-bath studies). MAO inhibitors (clorgyline and selegiline) attenuated ROS production by 50% and partially normalized the endothelium-dependent relaxation in diseased vessels. In conclusion, MAOs, in particular the MAO-B isoform, are induced in aortas and hearts in the streptozotocin-induced diabetic rat model and contribute, via the generation of H2O2, to the endothelial dysfunction associated with experimental diabetes. |
| Databáze: | OpenAIRE |
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