RGD Reference Report - Upregulation of acyl-CoA: cholesterol acyltransferase in chronic renal failure. - Rat Genome Database

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Upregulation of acyl-CoA: cholesterol acyltransferase in chronic renal failure.

Authors: Liang, K  Vaziri, ND 
Citation: Liang K and Vaziri ND, Am J Physiol Endocrinol Metab 2002 Oct;283(4):E676-81.
RGD ID: 625687
Pubmed: PMID:12217884   (View Abstract at PubMed)
DOI: DOI:10.1152/ajpendo.00364.2001   (Journal Full-text)

Chronic renal failure (CRF) is associated with profound abnormalities of lipid metabolism and accelerated arteriosclerotic cardiovascular disease. In a recent study, we found marked downregulation of hepatic lecithin-cholesterol acyltransferase, or LCAT, expression, which can account for impaired HDL maturation and depressed HDL cholesterol concentration in CRF. Here, we report on the effect of CRF on acyl-CoA:cholesterol acyltransferase (ACAT) expression. ACAT is an intracellular enzyme that catalyzes esterification of free cholesterol to cholesterol ester for storage or secretion. ACAT plays a major role in hepatic production and release of VLDL, intestinal absorption of cholesterol, foam cell formation, and atherogenesis. We examined hepatic expression of ACAT-1 and ACAT-2 mRNA (Northern blot) and protein (Western blot) abundance and total ACAT activity in male CRF rats (6 wk after 5/6 nephrectomy) and sham-operated controls. The CRF animals showed a significant reduction in creatinine clearance, marked hypertriglyceridemia, modest hypercholesterolemia, and significant upregulation of hepatic tissue ACAT-2 protein and mRNA abundance. In contrast, hepatic ACAT-1 mRNA and protein abundance were unaffected by CRF. Upregulation of ACAT-2 expression was accompanied by a significant increase in hepatic ACAT activity and a significant decrease in hepatic microsomal and whole liver free cholesterol concentration. Thus CRF results in significant upregulation of hepatic ACAT-2 (but not ACAT-1) expression and ACAT activity, which may, in part, contribute to the associated lipid disorders.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
end stage renal disease  ISOSoat2 (Rattus norvegicus)625687; 625687 RGD 
end stage renal disease  IDA 625687 RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cholesterol metabolic process  IDA 625687 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
sterol O-acyltransferase activity  IDA 625687 RGD 

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
kidney failure pathway  ISOSoat2 (Rattus norvegicus)625687; 625687 RGD 
kidney failure pathway  IDA 625687 RGD 
Objects Annotated

Genes (Rattus norvegicus)
Soat2  (sterol O-acyltransferase 2)

Genes (Mus musculus)
Soat2  (sterol O-acyltransferase 2)

Genes (Homo sapiens)
SOAT2  (sterol O-acyltransferase 2)

Objects referenced in this article
Gene Soat1 sterol O-acyltransferase 1 Rattus norvegicus

Additional Information