Background: Gestational diabetes (GDM) has long-term consequences for the offspring. Sirtuins (SIRTs) are associated with vascular and metabolic functions. We studied the impact of GDM on SIRT activity and expression in fetal endothelial colony-forming cells (ECFCs) and human umbilical vein endothelial cells (HUVECs) from pregnancies complicated by GDM. Methods: ECFCs and HUVECs were isolated from cord and cord blood of 10 uncomplicated pregnancies (NPs) and 10 GDM pregnancies. Nicotinamidadenindinukleotid (NAD + ) concentration, SIRT1 and SIRT3 activity, transcription levels of SIRT1, SIRT3, and SIRT4, and protein levels of SIRT1, SIRT3, and SIRT4 were determined in vitro with or without SIRT activators resveratrol (RSV) and paeonol. results: Fetal ECFCs from GDM pregnancies showed a decreased NAD + concentration, reduced SIRT1 and SIRT3 activity, and lower transcription levels of SIRT1, SIRT3, and SIRT4. HUVECs from GDM pregnancies had decreased NAD + concentrations and transcription levels of SIRT1 and SIRT4. RSV markedly enhanced the expression and activity of SIRTs in ECFCs and HUVECs, while paeonol was active only in ECFCs. conclusion: A reduction of SIRT activity and expression in fetal endothelial cells provides potential mechanistic insights into the pathophysiology of long-term cardiovascular complications observed in the offspring of GDM pregnancies. SIRT activators can increase SIRT activity in ECFCs, which opens perspectives for new therapeutic targets. a dverse events during fetal life have been implicated to induce fetal programming, which can result in chronic diseases (1). Especially gestational diabetes (GDM) of the mother has been associated with cardiovascular disease, metabolic syndrome, and obesity during later life in the offspring (2,3). The pathophysiological processes responsible for these late complications are largely unknown.Sirtuins (SIRTs) are important regulators of aging and metabolic diseases (4,5). Mammalian SIRTs belong to the histone deacetylase class III family comprising seven members (SIRT1-7), which require Nicotinamidadenindinukleotid (NAD + ) for their enzymatic activity (6). SIRT1 downregulation has been observed in peripheral blood mononuclear cells of individuals with impaired glucose tolerance (7,8). SIRT1 is known to regulate vascular endothelial cell functions (9). Furthermore, in vitro and in vivo studies demonstrated that a reduction in the number of endothelial progenitor cells (EPCs) under hyperglycemia is associated with reduced SIRT1 levels and activity (8,10). Endothelial cells regulate vascular tone and are the first fetal cells exposed to maternal hyperglycemia.In recent years, it has become evident that SIRT1 is a key player of EPC dysfunction in insulin resistance and metabolic syndrome (7,10,11). Overexpression of endothelium-specific SIRT1 protects against endothelial dysfunction induced by a high-fat diet and hyperglycemia (12,13). Recently, resveratrol (RSV) and paeonol (2′-Hydroxy-4′-methoxyacetophenone) have been shown to activate SIRTs and thus c...
Our data reveal a selective downregulation of the p110alpha catalytic isoform. This correlated with a slight decrease in PI3K activity as judged by the levels of phosphorylated Akt. CONCLUSION As PI3K are involved in signal transduction of various leukocyte receptors, this downregulation may comprise a means of holding immune functions at bay.
Im Israel-Palästina-Konflikt spielen Grenzziehungen nicht nur auf territorialer Ebene eine Rolle, sondern sie (be-)treffen genauso die (Über-)Lebenspraktiken der Menschen vor Ort. Der Konflikt ist damit ein Paradebeispiel für gegenläufige Erinnerungskonstruktionen entlang einseitig definierter Grenzen. Kulturelle Projekte wie beispielsweise das (mittlerweile geschlossene) »Cinema Jenin« und das »Freedom Theatre« geben Aufschluss über Widersprüche und Dynamiken von (gewaltfreiem) Widerstand, Gegen-Erzählungen und Dialog. Anne Rohrbach zeigt, wie kulturelle Projekte Frei-Räume in einer fragmentierten Gesellschaft öffnen und einen wichtigen Beitrag dazu leisten können, translokale Erinnerungs- und Widerstandsräume zu etablieren.
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