Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Gene expression in liver tissues derived from wild-type and Siglec-E-deficient mice at 55 weeks of age

ABSTRACT: We show that mice lacking Siglec-E, the main member of the CD33rSiglec family, exhibit reduced survival. Removal of Siglec-E causes the development of exaggerated signs of aging at the molecular, structural, and cognitive level. We found that accelerated aging was related both to an unbalanced ROS metabolism, and to a secondary impairment in detoxification of reactive molecules, ultimately leading to increased damage to cellular DNA, proteins and lipids. Taken together, our data suggest that CD33rSiglecs co-evolved in mammals to achieve a better management of oxidative stress during inflammation, which in turn reduces molecular damage and extends lifespan. Total RNA obtained from liver tissues from two wild-type and three Siglec-E-deficient mice

ORGANISM(S): Mus musculus

SUBMITTER: Ajit Varki

PROVIDER: E-GEOD-64760 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Siglec receptors impact mammalian lifespan by modulating oxidative stress.

Schwarz Flavio F Pearce Oliver M T OM Wang Xiaoxia X Samraj Annie N AN Läubli Heinz H Garcia Javier O JO Lin Hongqiao H Fu Xiaoming X Garcia-Bingman Andrea A Secrest Patrick P Romanoski Casey E CE Heyser Charles C Glass Christopher K CK Hazen Stanley L SL Varki Nissi N Varki Ajit A Gagneux Pascal P

eLife 20150407

Aging is a multifactorial process that includes the lifelong accumulation of molecular damage, leading to age-related frailty, disability and disease, and eventually death. In this study, we report evidence of a significant correlation between the number of genes encoding the immunomodulatory CD33-related sialic acid-binding immunoglobulin-like receptors (CD33rSiglecs) and maximum lifespan in mammals. In keeping with this, we show that mice lacking Siglec-E, the main member of the CD33rSiglec fa ...[more]

PMID: 25846707

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Project description:OBJECTIVE: The liver X receptor M-NM-1 (LXRM-NM-1) is a ligand-dependent nuclear receptor and the major regulator of reverse cholesterol transport in macrophages. This makes it an interesting target for mechanistic study and treatment of atherosclerosis. METHODS AND RESULTS: We optimized a promising stilbenoid structure (STX4) in order to reach nanomolar effective concentrations in LXRM-NM-1 reporter-gene assays. STX4 displayed the unique property to activate LXRM-NM-1 effectively but not its subtype LXRM-NM-2. The potential of STX4 to increase transcriptional activity as an LXRM-NM-1 ligand was tested with gene expression analyses in THP1-derived human macrophages and oxLDL-loaded human foam cells. Only in foam cells but not in macrophage cells STX4 treatment showed athero-protective effects with similar potency as the synthetic LXR ligand T0901317 (T09). Surprisingly, combinatorial treatment with STX4 and T09 resulted in an additive effect on reporter-gene activation and target gene expression. In physiological tests the cellular content of total and esterified cholesterol was significantly reduced by STX4 without the undesirable increase in triglyceride levels as observed for T09. CONCLUSIONS: STX4 is a new LXRM-NM-1-ligand to study transcriptional regulation of anti-atherogenic processes in cell or ex vivo models, and provides a promising lead structure for pharmaceutical development. 2 treatment groups (STX4 vs. DMSO in foam cells), 3 biological replicates per treatment (6 samples in total), each representing one well from cell culture plate 2 treatment groups (STX4 vs. DMSO in macrophages), 4 biological replicates per treatment (8 samples in total), each representing one well from cell culture plate 2 treatment groups (T0901317 vs. DMSO in foam cells), 3-4 biological replicates per treatment (7 samples in total), each representing one well from cell culture plate 2 treatment groups (T0901317 vs. DMSO in macrophages), 4 biological replicates per treatment (8 samples in total), each representing one well from cell culture plate

Dataset Information

Gene expression in liver tissues derived from wild-type and Siglec-E-deficient mice at 55 weeks of age

Publications

Siglec receptors impact mammalian lifespan by modulating oxidative stress.

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