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

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概要

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• 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 m 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 4 days, 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.

• 2009-12-25

著者

• Hara Atsushi

  愛知県がんセンター研究所 分子病態学部

• Hara Atsushi

  Department Of Biochemistry Division Of Neuro-aging Research Center On Aging And Adaptation Shinshu U

• SHENG Xiaona

  Department of Metabolic Regulation, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine

• Nakajima Takero

  Department Of Metabolic Regulation Institute On Aging And Adaptation Shinshu University Graduate School Of Medicine

• Zhang Xiaowei

  Department Of Metabolic Regulation Institute On Aging And Adaptation Shinshu University Graduate School Of Medicine

• Kyogashima Mamoru

  Division Of Microbiology And Molecular Cell Biology Nihon Pharmaceutical University

関連論文

• 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
• Chemical and Apoptotic Properties of Hydroxy-Ceramides Containing Long-Chain Bases with Unusual Alkyl Chain Lengths
• Preparation of Various Lysogangliosides Including Lyso-Fucosyl GM1 and Delayed Extraction Matrix-Assisted Laser Desorption Ionization Time-of -Flight Mass Spectrometric Analysis
• Rapid Method of Preparation of Lysoglycosphingolipids and Their Confirmation by Delayed Extraction Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry
• Attenuation of Kidney Injuries Maintains Serum Sulfatide Levels Dependent on Hepatic Synthetic Ability: A Possible Involvement of Oxidative Stress
• Long-term improvement of oxidative stress via kidney transplantation ameliorates serum sulfatide levels

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