Transcriptom and miRNA data of PUFA-enriched stimulated murine macrophage and human endothelial cell lines.

Inflammation is associated with the adaptation of macrophages and endothelial cells, and the dysregulation of these differentiation processes has been directly linked to both acute and chronic disease states. As cells in constant contact with blood, macrophages and endothelial cells are also under the direct influence of immunomodulatory dietary components such as polyunsaturated fatty acids (PUFA). RNA sequencing analyses allow us to understand the global changes in gene expression occurring during cell differentiation, including both transcriptional (transcriptome) and post-transcriptional (miRNAs) levels.

Septic-Induced microRNA Expression Modulations Are Linked to Angiogenesis, Vasomotion, and Hypoxia-Induced Processes.

Sepsis is an exaggerated immune reaction to an infection, which leads to organ dysfunction especially circulatory failure. This is based on cellular processes, which are regulated by post-transcriptional gene expression modulations including microRNAs (miRNAs). In order to elucidate the role miRNAs play in septic processes, monocytes and endothelial cells were grown in an inflammatory milieu.

A Master Switch in Thiopeptide Biosynthesis.

Although considerable knowledge of the biosynthetic machinery of thiopeptide antibiotics has been accumulated, the regulation of their production remains unclear. In this issue of Cell Chemical Biology, Li et al. (2018) have now characterized a key transcription factor and suggest its feedback regulation by biosynthesis intermediates and the final product.

Lipid raft localization of TLR2 and its co-receptors is independent of membrane lipid composition.

Background: Toll like receptors (TLRs) are an important and evolutionary conserved class of pattern recognition receptors associated with innate immunity. The recognition of Gram-positive cell wall constituents strongly depends on TLR2. In order to be functional, TLR2 predominantly forms a heterodimer with TLR1 or TLR6 within specialized membrane microdomains, the lipid rafts.

Impact of Polyunsaturated Fatty Acids on miRNA Profiles of Monocytes/Macrophages and Endothelial Cells-A Pilot Study.

Alteration of miRNAs and dietary polyunsaturated fatty acids (PUFAs) underlies vascular inflammation. PUFAs are known to be incorporated into the cell membrane of monocytes/macrophages or endothelial cells, the major cellular players of vascular diseases, thereby affecting cellular signal transduction. Nevertheless, there are no investigations concerning the PUFA impact on miRNA expression by these cells.

A continuous sirtuin activity assay without any coupling to enzymatic or chemical reactions.

Sirtuins are NAD(+) dependent lysine deacylases involved in many regulatory processes such as control of metabolic pathways, DNA repair and stress response. Modulators of sirtuin activity are required as tools for uncovering the biological function of these enzymes and as potential therapeutic agents. Systematic discovery of such modulators is hampered by the lack of direct and continuous activity assays.

A Novel Continuous Assay for the Deacylase Sirtuin 5 and Other Deacetylases.

Sirtuins are NAD(+) dependent lysine deacylases involved in many regulatory processes like control of metabolic pathways, DNA repair, and stress response. Modulators of sirtuin activity are needed as tools for uncovering the biological function of these enzymes and as potential therapeutics. Systematic discovery of such modulators is hampered by the lack of efficient and simple continuous activity assays running at low sirtuin concentrations in microtiter plates.

Selective Sirt2 inhibition by ligand-induced rearrangement of the active site.

Sirtuins are a highly conserved class of NAD(+)-dependent lysine deacylases. The human isotype Sirt2 has been implicated in the pathogenesis of cancer, inflammation and neurodegeneration, which makes the modulation of Sirt2 activity a promising strategy for pharmaceutical intervention. A rational basis for the development of optimized Sirt2 inhibitors is lacking so far.

Chemical probing of the human sirtuin 5 active site reveals its substrate acyl specificity and peptide-based inhibitors.

Sirtuins are NAD(+)-dependent deacetylases acting as sensors in metabolic pathways and stress response. In mammals there are seven isoforms. The mitochondrial sirtuin 5 is a weak deacetylase but a very efficient demalonylase and desuccinylase; however, its substrate acyl specificity has not been systematically analyzed.

New assays and approaches for discovery and design of Sirtuin modulators.

Introduction: Sirtuins are an evolutionarily conserved family of NAD(+)-dependent protein lysine deacylases. In mammals, 7 Sirtuin isoforms control various functions in metabolism, stress responses and aging processes. Sirtuins are considered attractive therapeutic targets for metabolic and aging-related diseases, such as metabolic syndrome and neurodegenerative disorders.