RESUMEN
We studied the changes in proteasomal proteolisis during modelling of rabbit cholesterol-induced atherosclerosis. It was determined that in aorta the TL activity of proteasome increased 2.4-fold (P < 0.05), CTL activity increased by 43%, and PGPG--by 10%. In heart tissue it was observed the increase of CTL proteasome activity by 14%. The application of "Korvitin" (water-soluble form of quercetine) followed by considerable decrease of proteasomal activity both in tissues (aorta and heart) and leucocytes. The intensity ofatherosclerotic changes in aorta was significantly smaller. Obtained data suggest that "Korvitin" reveales angioprotective properties mediated by it effect on proteasomal proteolisis.
Asunto(s)
Antioxidantes/uso terapéutico , Aorta/efectos de los fármacos , Aterosclerosis/prevención & control , Leucocitos/metabolismo , Miocardio/metabolismo , Complejo de la Endopetidasa Proteasomal/metabolismo , Quercetina/uso terapéutico , Animales , Antioxidantes/administración & dosificación , Aorta/metabolismo , Aorta/patología , Aterosclerosis/sangre , Aterosclerosis/metabolismo , Aterosclerosis/patología , Colesterol en la Dieta/administración & dosificación , Modelos Animales de Enfermedad , Femenino , Linfocitos/metabolismo , Masculino , Monocitos/metabolismo , Miocardio/patología , Neutrófilos/metabolismo , Quercetina/administración & dosificación , Conejos , SolubilidadRESUMEN
In experiments on the primary culture of isolated neonatal rat cardiomyocytes it was determined that cardiomyocytes express ALOX5 gene encoding enzyme 5-lipoxygenase. Anoxia-reoxygenation does not affect significantly the expression of 5-lipoxygenase mRNA in cardiomyocytes. Transfection of 5-lipoxygenase-specific small interfering RNA's (siRNA) into cardiomyocytes lead to a significant reduction of 5-lipoxygenase mRNA expression in cardiomyocytes 24 hours after transfection. ALOX5 gene silencing resulted in improved viability of cell population (by 13.3% P < 0.001) due to decreased number of necrotic (by 14.6%, P < 0.001), but not apoptotic, cells during anoxia-reoxygenation. Our results indicate that siRNA against ALOX5 effectively protects cardiomyocytes against anoxia-reoxygenation injury.