Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05109 (S100A8)
 1,212 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Meta-analysis methods exist for combining multiple microarray datasets. However, there are a wide range of issues associated with microarray meta-analysis and a limited ability to compare the performance of different metaanalysis methods. Using cDNA microarray technology (Partek Genomics Suite 6.6) and global pathway analysis with Ingenuity Pathway Analysis tool (IPA, Inc), we examined the transcript level in type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) patients and controls. To understand the molecular link between T2DM and AD, we compared the gene expression pattern and pathway involved. Microarray analysis identified 235 differentially expressed genes between T2DM patients and controls; and 834 between AD and controls at two fold change and a false discovery rate of 0.05. Significantly changed expression of "myeloid leukemia cell differentiation protein 1; RAS guanyl releasing protein 1; S100 calcium-binding protein A8; prostaglandin- endoperoxide synthase 2; parvalbumin; endoplasmic reticulum aminopeptidase 1; phosphoglycerate kinase 1; Eukaryotic translation initiation factor 3 subunit F; Interleukin-1 beta; tubulin, beta 2A; glycine receptor alpha 1 and ribosomal protein S24" genes were highly associated with T2DM, whereas "neuronal differentiation 6; G-protein coupled receptor 83; phosphoserine phosphatase; bobby sox homolog or HMG box -containing protein 2; Glutathione S-transferase theta 1; alpha-2-glycoprotein 1 zinc-binding; Heat shock 70kDa protein 1B; transportin 1, Acidic leucine-rich nuclear phosphoprotein 32 family member B; Nuclear factor of activated T-cells 5; inositol 1,4,5-trisphosphate 3-kinase B; prenylcysteine oxidase 1 like" were found to be strongly related with AD. We also found a set of differentially expressed genes; "ARP2 actin-related protein 2; Cell division control protein 42; cytoplasmic polyadenylation element binding protein 4; Early growth response protein 1; ectonucleotide pyrophosphatase/phosphodiesterase 5; folate receptor 1; glutamate-ammonia ligase; hydroxy-3-methylglutaryl-Coenzyme A reductase; 3-hydroxy-3- methylglutaryl-CoA synthase; interleukin 1 receptor- like 1; leukemia inhibitory factor receptor; metastasis associated lung adenocarcinoma transcript 1; pyruvate dehydrogenase kinase, isozyme 4; phosphoserine phosphatase, parvalbumin, and tubulin, beta 2A" to be present in both dataset. Altered regulation of intracellular signaling pathways, including Ephrin receptor, liver X receptor/ retinoid X receptor; interleukin 6; insulinlike growth factor 1; interleukin 10 and 14-3-3-mediated signaling pathways were associated with T2DM as well as Alzheimer-type pathology. Our findings implicate diabetic disorders in the pathogenesis of AD, and provide a basis for future candidate studies based on specific pathways.
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PMID:Establishing genomic/transcriptomic links between Alzheimer's disease and type 2 diabetes mellitus by meta-analysis approach. 2405 8

Impaired erythropoiesis in the deletion 5q (del(5q)) subtype of myelodysplastic syndrome (MDS) has been linked to heterozygous deletion of RPS14, which encodes the ribosomal protein small subunit 14. We generated mice with conditional inactivation of Rps14 and demonstrated an erythroid differentiation defect that is dependent on the tumor suppressor protein p53 (encoded by Trp53 in mice) and is characterized by apoptosis at the transition from polychromatic to orthochromatic erythroblasts. This defect resulted in age-dependent progressive anemia, megakaryocyte dysplasia and loss of hematopoietic stem cell (HSC) quiescence. As assessed by quantitative proteomics, mutant erythroblasts expressed higher levels of proteins involved in innate immune signaling, notably the heterodimeric S100 calcium-binding proteins S100a8 and S100a9. S100a8--whose expression was increased in mutant erythroblasts, monocytes and macrophages--is functionally involved in the erythroid defect caused by the Rps14 deletion, as addition of recombinant S100a8 was sufficient to induce a differentiation defect in wild-type erythroid cells, and genetic inactivation of S100a8 expression rescued the erythroid differentiation defect of Rps14-haploinsufficient HSCs. Our data link Rps14 haploinsufficiency in del(5q) MDS to activation of the innate immune system and induction of S100A8-S100A9 expression, leading to a p53-dependent erythroid differentiation defect.
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PMID:Rps14 haploinsufficiency causes a block in erythroid differentiation mediated by S100A8 and S100A9. 2687 32