| Autor: |
Silvana Hrelia, Paola Rizzo, Aldo Roda, Massimo Guardigli, J Shehu, Cristiana Caliceti, Giorgio Aquila, Francesca Fortini, Benedetta Rizzo, Roberto Ferrari, Emanuela Leoncini, Arrigo F G Cicero, Laura Zambonin |
| Přispěvatelé: |
EAS, Cicero, A, Caliceti, C, Rizzo, P, Ferrari, R, Fortini, F, Aquila, G, Shehu, J, Leoncini, E, Zambonin, L, Rizzo, B, Guardigli, M, Roda, A, Hrelia, S, DIPARTIMENTO DI CHIMICA 'GIACOMO CIAMICIAN', DIPARTIMENTO DI FARMACIA E BIOTECNOLOGIE, DIPARTIMENTO DI SCIENZE BIOMEDICHE E NEUROMOTORIE, DIPARTIMENTO DI SCIENZE MEDICHE E CHIRURGICHE, DIPARTIMENTO DI SCIENZE PER LA QUALITA' DELLA VITA, Facolta' di FARMACIA, AREA MIN. 06 - Scienze mediche, AREA MIN. 05 - Scienze biologiche, Da definire, AREA MIN. 03 - Scienze chimiche |
| Jazyk: |
angličtina |
| Rok vydání: |
2016 |
| Předmět: |
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| Popis: |
none 13 no Objectives: Oxidized LDL (oxLDL) or pro-inflammatory stimuli lead to increased oxidative stress linked to endothelial dysfunction and atherosclerosis. The oxLDL receptor-1 (LOX1) is elevated within atheromas and cholesterol-lowering statins also inhibit LOX1 expression. Berberine (BBR), an alkaloid extracted from plants of gender Berberis, has lipid-lowering and anti-inflammatory activity. However, its role in regulating LOX1- mediated signalling is still unknown. The aim of this study was to compare the effects of BBR and lovastatin (LOVA) on oxLDL- and TNFa-induced endothelial dysfunction in human umbilical vein endothelial cells (HUVECs). Methods: Cytotoxicity was determined by LDH assay. Antioxidant capacity was measured with chemiluminescent and ORAC method and intracellular ROS levels in HUVECs through a fluorescent dye. Gene and protein expression levels were assayed by qRT-PCR and western blot, respectively. Results: HUVECs exposure to oxLDL (30mg/ml) or TNFa (10ng/ml) for 24h led to a significant increase in LOX1 expression, effect abrogated by BBR (5mM) and LOVA (1mM). BBR but not LOVA treatment abolished the TNFa induced cytotoxicity and restored the activation of Akt signalling. Although both compounds reduced intracellular ROS levels induced by H2O2 (100mM) or TNFa, only BBR inhibited NOX2 expression, MAPK/Erk signalling and subsequent NF-kB e related genes VCAM and ICAM expression, induced by TNFa. Conclusions: These findings demonstrated for the first time that BBR could prevent the oxLDL and TNFa - induced LOX1 expression and oxidative stress, key events that lead to NOX2, MAPK/Erk and NF-kB activation linked to endothelial dysfunction. Cicero, A; Caliceti, C; Rizzo, P; Ferrari, R; Fortini, F; Aquila, G; Shehu, J; Leoncini, E; Zambonin, L; Rizzo, B; Guardigli, M; Roda, A; Hrelia, S Cicero, A; Caliceti, C; Rizzo, P; Ferrari, R; Fortini, F; Aquila, G; Shehu, J; Leoncini, E; Zambonin, L; Rizzo, B; Guardigli, M; Roda, A; Hrelia, S |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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