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• W2896576499 abstract "Type 2 diabetes is associated with major vascular dysfunctions, leading to clinical complications such as stroke. It is also known that hyperglycemia dysregulates blood-brain barrier homeostasis by altering cerebral endothelial cell function. Oxidative stress may play a critical role. The aim of this study was to evaluate the effect of hyperglycemia and insulin on the production of redox, inflammatory and vasoactive markers by cerebral endothelial cells. Murine bEnd.3 cerebral endothelial cells were exposed to hyperglycemia in the presence or not of insulin. Results show that hyperglycemia altered the expression of genes encoding the ROS-producing enzyme Nox4, antioxidant enzymes Cu/ZnSOD, catalase and HO-1 as well as Cu/ZnSOD, MnSOD and catalase enzymatic activities, leading to a time-dependent modulation of ROS levels. Cell preconditioning with inhibitors targeting PI3K, JNK, ERK, p38 MAPK or NFĸB signaling molecules partly blocked hyperglycemia-induced oxidative stress. Conversely, AMPK inhibitor exacerbated ROS production, suggesting a protective role of AMPK on the antioxidant defense system. Hyperglycemia also modulated both gene expression and nuclear translocation of the redox-sensitive transcription factor Nrf2. Moreover, hyperglycemia caused a pro-inflammatory response by activating NFĸB-AP-1 pathway and IL-6 secretion. Hyperglycemia reduced eNOS gene expression and NO levels, while increasing ET-1 gene expression. Importantly, insulin counteracted all the deleterious effects of hyperglycemia. Collectively, these results demonstrate that hyperglycemia dysregulated redox, inflammatory and vasoactive markers in cerebral endothelial cells. Insulin exerted a protective action against hyperglycemia effects. Thus, it will be of high interest to evaluate the benefits of antioxidant and anti-inflammatory strategies against hyperglycemia-mediated vascular complications in type 2 diabetes." @default.
• W2896576499 created "2018-10-26" @default.
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• W2896576499 date "2019-01-01" @default.
• W2896576499 modified "2023-10-16" @default.
• W2896576499 title "Hyperglycemia modulates redox, inflammatory and vasoactive markers through specific signaling pathways in cerebral endothelial cells: Insights on insulin protective action" @default.
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• W2896576499 doi "https://doi.org/10.1016/j.freeradbiomed.2018.10.430" @default.
• W2896576499 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30359759" @default.
• W2896576499 hasPublicationYear "2019" @default.
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