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Acute kidney injury induced by protein-overload nephropathy down-regulates gene expression of hepatic cerebroside sulfotransferase in mice, resulting in reduction of liver and serum sulfatides.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2009 Dec 25; Vol. 390 (4), pp. 1382-8. Date of Electronic Publication: 2009 Nov 04. - Publication Year :
- 2009
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Abstract
- Sulfatides, possible antithrombotic factors belonging to sphingoglycolipids, are widely distributed in mammalian tissues and serum. We recently found that the level of serum sulfatides was significantly lower in hemodialysis patients than that in normal subjects, and that the serum level closely correlated to the incidence of cardiovascular disease. These findings suggest a relationship between the level of serum sulfatides and kidney function; however, the molecular mechanism underlying this relationship remains unclear. In the present study, the influence of kidney dysfunction on the metabolism of sulfatides was examined using an established murine model of acute kidney injury, protein-overload nephropathy in mice. Protein-overload treatment caused severe proximal tubular injuries within 4days, and this treatment obviously decreased both serum and hepatic sulfatide levels. The sphingoid composition of serum sulfatides was very similar to that of hepatic ones at each time point, suggesting that the serum sulfatide level is dependent on the hepatic secretory ability of sulfatides. The treatment also decreased hepatic expression of cerebroside sulfotransferase (CST), a key enzyme in sulfatide metabolism, while it scarcely influenced the expression of the other sulfatide-metabolizing enzymes, including arylsulfatase A, ceramide galactosyltransferase, and galactosylceramidase. Pro-inflammatory responses were not detected in the liver of these mice; however, potential oxidative stress was increased. These results suggest that down-regulation of hepatic CST expression, probably affected by oxidative stress from kidney injury, causes reduction in liver and serum sulfatide levels. This novel mechanism, indicating the crosstalk between kidney injury and specific liver function, may prove useful for helping to understand the situation where human hemodialysis patients have low levels of serum sulfatides.
- Subjects :
- Acute Disease
Animals
Disease Models, Animal
Down-Regulation
Kidney Diseases chemically induced
Kidney Diseases genetics
Male
Mice
Mice, Mutant Strains
Oxidative Stress
PPAR alpha genetics
Proteins toxicity
Sulfoglycosphingolipids analysis
Sulfoglycosphingolipids blood
Gene Expression Regulation
Kidney Diseases enzymology
Liver metabolism
Sulfoglycosphingolipids metabolism
Sulfotransferases genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 390
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 19895791
- Full Text :
- https://doi.org/10.1016/j.bbrc.2009.10.164