Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Effect of squalene on liver transcriptome of mice lacking apolipoprotein E

ABSTRACT: The hypothesis that the squalene of olive oil might influence hepatic gene expression in an apoE and sex-dependent ways was tested in mice. Gene expression was analyzed using DNA microarrays in male apoE-deficient mice that received 1 g/kg/day of squalene for 10 weeks. As initial screening of potential candidate genes involved in a differential response, only genes with remarkably modified expression (signal log2 ratio > 1.5 or < -1.5) were further considered

ORGANISM(S): Mus musculus

SUBMITTER: Jesus Osada

PROVIDER: E-GEOD-36932 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Objective: Apolipoprotein E (Apo E) is a multifunctional protein, originally described in the context of lipoprotein metabolism and cardiovascular disease. More recently, anti-inflammatory functions of ApoE have been documented. ApoE was studied in the context of several inflammatory disorders, but its role in the pathogenesis of acute organ rejection is unknown. In this study, we test the hypothesis that ApoE attenuates acute renal allograft rejection. Materials and methods: The Dark Agouti (DA) to Lewis (Lew) and the Brown Norway (BN) to Lew rat strain combinations were used to investigate fatal acute rejection. In addition, Fischer 344 (F344) kidneys were transplanted to Lew rats to study reversible acute rejection. Isograft recipients and untreated Lew rats were used as controls. ApoE mRNA expression was quantified in intravascular leukocytes accumulating in the blood vessels of renal grafts and in graft tissue. Apo E protein levels were assessed in blood plasma. To test the protective potential of ApoE, recipients of BN kidneys were treated with ApoE-mimetic peptide. Results: Intravascular graft leukocytes and renal tissue obtained from animals undergoing reversible acute rejection expressed increased levels of ApoE mRNA, whereas during fatal rejection, ApoE expression remained unchanged in the BN to Lew rat strain combination or was significantly reduced when DA rats were used as donors of the kidney. On the protein level, no changes in ApoE were seen in plasma. However, we do not know if local leukocytic ApoE expression results in increased ApoE concentrations inside graft blood vessels. Peptide treatment of allograft recipients reversed fatal rejection and significantly improved animal survival. Conclusions: ApoE plays a protective role in acute organ rejection. Further studies are needed to understand the exact mechanism how ApoE reverses acute rejection. dual-color balanced dye-swap design with 4 biological replicates, hybridized on 4 arrays

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Effect of squalene on liver transcriptome of mice lacking apolipoprotein E

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