Cholesterol Metabolism by Uncultured Human Gut Bacteria Influences Host Cholesterol Level
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA755357 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR19583600.fastq.gz | Fastqsanger.gz | |||
| SRR19583900_1.fastq.gz | Fastqsanger.gz | |||
| SRR19583900_2.fastq.gz | Fastqsanger.gz | |||
| SRR19584100_1.fastq.gz | Fastqsanger.gz |
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Project description:High cholesterol diet and xenobiotic treatment induce changes in cholesterol homeostasis and drug metabolism. Mice were either 7 days on high cholesterol diet or were treated with phenobarbital. Liver samples were analyzed using Sterolgene v0 cDNA microarrays. Sterolgene microarray is a tool designed to enable focused studies of cholesterol homeostasis and drug metabolism. We show that one week of cholesterol diet down-regulates cholesterol biosynthesis and up-regulates xenobiotic metabolism (Cyp3 family). Phenobarbital treatment also up-regulates xenobiotic metabolism (Cyp2b and Cyp3a families). We can conclude that the Sterolgene series of cDNA microarrays represent novel original tool, enabling focused and cost-wise studies of cholesterol homeostasis and drug metabolism. Keywords: Treatment and diet effects One group of mice was treated i.p. with 50 mg/kg of phenobarbital in vehicle (5% DMSO in corn oil). Untreated group was injected vehicle. Third group was 7 days on 1 % (w/w) cholesterol diet prior vehicle treatment. After 10 h animals were sacrificed and livers were stored. Pools of total RNA from two animals were mixed. Three pools of untreated and phenobarbital treated groups, and two pools of cholesterol diet group were co-hybridized with liver reference on Sterolgene v0 cDNA microarray. No dye-swaps were performed.
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Project description:High cholesterol diet and xenobiotic treatment induce changes in cholesterol homeostasis and drug metabolism. Mice were either 7 days on high cholesterol diet or were treated with phenobarbital. Liver samples were anayzed using Affymetrix GeneChip MOE430A. Keywords: treatment and diet effects
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Project description:PICALM (Phosphatidyl Inositol Clathrin Assembly Lymphoid Myeloid protein) is a ubiquitously expressed protein that plays a role in clathrin-mediated endocytosis. PICALM also affects the internalization of SNAREs and modulates macroautophagy. Chromosomal translocations that result in the fusion of PICALM to heterologous proteins cause leukemias, and genome-wide association studies have linked Single Nucleotide Polymorphisms (SNPs) of PICALM to Alzheimer’s disease. To obtain insight into the biological role of PICALM, we performed gene expression studies of PICALM-deficient and PICALM-expressing cells. Pathway analysis demonstrated that PICALM expression influences the expression of genes that encode proteins involved in cholesterol biosynthesis and lipoprotein uptake. GC-MS studies indicated that loss of PICALM increases total cholesterol pool size. Isotopic labeling studies revealed that loss of PICALM alters cholesterol homeostasis via increased scavenging of cholesterol. Measurement of LDL receptor endocytosis further showed that PICALM deficient cells express higher LDLR levels resulting in higher lipoprotein internalization. These findings suggest that PICALM is required for cellular cholesterol homeostasis and point to a novel mechanism by which PICALM alterations may contribute to disease. Total RNA was isolated (Qiagen RNeasy® Micro kit, Valencia, CA) from four replicates of PICALM knockout cells transfected with control vector, and from four replicates of PICALM knockout cells transfected with PICALM.
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Project description:Cholesterol Metabolism by Uncultured Human Gut Bacteria Influences Host Cholesterol Level.
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Project description:PICALM (Phosphatidyl Inositol Clathrin Assembly Lymphoid Myeloid protein) is a ubiquitously expressed protein that plays a role in clathrin-mediated endocytosis. PICALM also affects the internalization of SNAREs and modulates macroautophagy. Chromosomal translocations that result in the fusion of PICALM to heterologous proteins cause leukemias, and genome-wide association studies have linked Single Nucleotide Polymorphisms (SNPs) of PICALM to Alzheimer’s disease. To obtain insight into the biological role of PICALM, we performed gene expression studies of PICALM-deficient and PICALM-expressing cells. Pathway analysis demonstrated that PICALM expression influences the expression of genes that encode proteins involved in cholesterol biosynthesis and lipoprotein uptake. GC-MS studies indicated that loss of PICALM increases total cholesterol pool size. Isotopic labeling studies revealed that loss of PICALM alters cholesterol homeostasis via increased scavenging of cholesterol. Measurement of LDL receptor endocytosis further showed that PICALM deficient cells express higher LDLR levels resulting in higher lipoprotein internalization. These findings suggest that PICALM is required for cellular cholesterol homeostasis and point to a novel mechanism by which PICALM alterations may contribute to disease.
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