Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The variable predisposition to cachexia may, in part, be due to the interaction of host genotype. We analyzed 129 single nucleotide polymorphisms (SNPs) in 80 genes for association with cachexia based on degree of weight loss (>5, >10, >15%) as well as weight loss in the presence of systemic inflammation (C-reactive protein, > 10 mg/l). 775 cancer patients were studied with a validation association study performed on an independently recruited cohort (n = 101) of cancer patients. The C allele (minor allele frequency 10.7%) of the rs6136 (SELP) SNP was found to be associated with weight loss >10% both in the discovery study (odds ratio (OR) 0.52; 95% confidence intervals (CI), 0.29-0.93; p = 0.026) and the validation study (OR 0.09, 95% CI 0.01-0.98, p = 0.035). In separate studies, induction of muscle atrophy gene expression was investigated using qPCR following either tumour-induced cachexia in rats or intra-peritoneal injection of lipopolysaccharide in mice. P-selectin was found to be significantly upregulated in muscle in both models. Identification of P-selectin as relevant in both animal models and in cachectic cancer patients supports this as a risk factor/potential mediator in cachexia.
 ...
PMID:P-selectin genotype is associated with the development of cancer cachexia. 2249 12

Bovine P-selectin (SELP) mediates leukocyte rolling and primes leukocyte adhesion to endothelium, both essential for leukocyte recruitment to an infection site. We investigated SELP-mediated adhesion between bovine peripheral blood leukocytes (PBLs) and cultured bovine aortic endothelial cells pre-activated with lipopolysaccharide (LPS). We examined gene polymorphism for bovine selectins SELP, l-selectin (SELL) and E-selectin (SELE) and compared their SNP frequency between five dairy breeds (Holstein, Friesian, Jersey, Ayrshire and Brown Swiss). LPS treatment caused a rapid (10min) and slower (4h) enhancement of PBL adhesion (P<0.01). Antibody blocking of SELP inhibited LPS induced cell adhesion. SELP was highly polymorphic, with 9 of the 13 SNPs in its exons, whereas only three synonymous SNPs in SELL and one in SELE. The resulting amino acid changes for the three missense SELP SNP were located in the lectin domain and in two consensus repeat (CR) regions, CR2 and CR5. The Val475Met variant locus in the CR4 and CR5 linking region was very close to a predicted N-acetyl-d-glucosamine glycosylation site, which is likely to influence SELP function. The AA genotype was under-represented, only being found in 1% of 373 heifers genotyped from the 5 breeds (P=0.056), suggesting that AA homozygous animals carrying the Val475Met substitution for SELP may have compromised development. Our study thus confirmed that SELP mediates the attachment of PBL to endothelium and provides novel evidence that its high polymorphism is likely to affect biological function. This may potentially influence leukocyte migration and fertility, both key to successful performance in dairy cows.
...
PMID:Bovine P-selectin mediates leukocyte adhesion and is highly polymorphic in dairy breeds. 2766 75

In sepsis, platelets may become activated via toll-like receptors (TLRs), causing microvascular thrombosis. Megakaryocytes (MKs) also express these receptors; thus, severe infection may modulate thrombopoiesis. To explore the relevance of altered miRNAs in platelet activation upon sepsis, we first investigated sepsis-induced miRNA expression in platelets of septic patients. The effect of abnormal Dicer level on miRNA expression was also evaluated. miRNAs were profiled in septic vs. normal platelets using TaqMan Open Array. We validated platelet miR-26b with its target SELP (P-selectin) mRNA levels and correlated them with clinical outcomes. The impact of sepsis on MK transcriptome was analyzed in MEG-01 cells after lipopolysaccharide (LPS) treatment by RNA-seq. Sepsis-reduced miR-26b was further studied using Dicer1 siRNA and calpain inhibition in MEG-01 cells. Out of 390 platelet miRNAs detected, there were 121 significantly decreased, and 61 upregulated in sepsis vs. controls. Septic platelets showed attenuated miR-26b, which were associated with disease severity and mortality. SELP mRNA level was elevated in sepsis, especially in platelets with increased mean platelet volume, causing higher P-selectin expression. Downregulation of Dicer1 generated lower miR-26b with higher SELP mRNA, while calpeptin restored miR-26b in MEG-01 cells. In conclusion, decreased miR-26b in MKs and platelets contributes to an increased level of platelet activation status in sepsis.
 ...
PMID:Reduced miR-26b Expression in Megakaryocytes and Platelets Contributes to Elevated Level of Platelet Activation Status in Sepsis. 3201 35