Unknown,Transcriptomics,Genomics,Proteomics

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Candidates for bile acid-dependent PPAR?-target genes in mouse intestinal cells

ABSTRACT: In addition to their role as a digestive detergent, bile acids have the ability to modulate the expression of genes. The intestinal content of cholic acids (CA) fluctuated in response to the daily feeding-fasting cycle; therefore, we hypothesized that the temporal accumulation of CA may affect the expression of genes in intestinal epithelial cells. To screen bile acid-regulated genes, we performed oligonucleotide microarray analyses using RNA isolated from the CA-treated intestinal cells of mice. Several types of genes were screened as candidates for bile acid-regulated genes. They included genes that encoded lipid metabolism-related proteins, receptors, transcriptional factors, and plasma-membrane transporters. Total 2 samples were derived from [1] vehicle (0.05% DMSO and 0.25% ethanol)-treated intestinal epithelial cells of mice and [2] cholic acid (CA)-treated intestinal epithelial cells of mice.

ORGANISM(S): Mus musculus

SUBMITTER: Satoru Koyanagi

PROVIDER: E-GEOD-55443 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:In order to successfully survive in and to colonize the gastrointestinal tract, bacteria need to develop strategies to overcome bile acid stress. The most prominent bile acids are the primary bile acids cholic acid (CA) and chenodeoxycholic acid (CDCA) as well as the secondary bile acid deoxycholic acid (DCA). In this study, we investigated the stress response of E. faecalis and E. faecium to sublethal concentrations of these three bile acids on the proteome level using DIA-MS. As both species showed similar IC50 for DCA and CDCA in growth experiments and both were highly resistant towards CA, we assumed similar changes to their protein expression profiles. Moreover, we investigated proteomic differences of E. faecalis grown under aerobic or microaerophilic conditions. Our findings showed similarities, but also species-specific variations in the response to the different bile acids, which reveal potential differences in the adaptation process. DCA and CDCA had a strong effect on down-expression of proteins involved in translation, transcription and replication in E. faecalis, but to a lesser extent in E. faecium. Proteins commonly significantly altered in their expression in all bile acid treated samples were identified for both species and represent a “general bile acid response”. Among these, ABC-transporters, multi-drug transporters and proteins related to cell wall biogenesis were up-expressed in both species and thus seem to play an essential role in bile acid resistance. Specific for all E. faecalis samples was the up-expression of several subunits of a V-type ATPase and the down-expression of proteins involved in pyruvate-, citrate- and folate metabolism. Most of the differentially expressed proteins were also identified when E. faecalis was incubated with low levels of DCA at microaerophilic conditions in comparison to aerobic conditions, indicating that adaptations to bile acids and to a microaerophilic atmosphere can occur simultaneously.

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Candidates for bile acid-dependent PPAR?-target genes in mouse intestinal cells

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