Attenuation of Kidney Injuries Maintains Serum Sulfatide Levels Dependent on Hepatic Synthetic Ability: A Possible Involvement of Oxidative Stress

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概要

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• Serum sulfatides are the major glycosphingolipids in lipoproteins. Although serum sulfatides are mainly synthesized and secreted by the liver, they are significantly decreased when the kidneys are impaired. Our recent experimental study using a murine protein-overload nephropathy model suggested a hypothetical mechanism whereby serum sulfatides were reduced due to kidney dysfunction. This was the result of decreased hepatic expression of a sulfatide synthetic enzyme, cerebroside sulfotransferase (CST), which is associated with systemic enhancement of oxidative stress. However, there is a possibility that the experimental process, protein-overload itself, directly affected the sulfatide metabolism and oxidative stress in the liver. To determine whether kidney dysfunction actually reduces the hepatic synthesis of sulfatides via oxidative stress, we examined sulfatide levels, the hepatic content of metabolic sulfatide enzymes, and the degree of oxidative stress in protein-overload mice subjected to renoprotective therapy using clofibrate, a representative hypolipidemic medicine. Protein-overload mice exhibited marked kidney injuries, enhancement of hepatic oxidative stress, decreased levels of serum and hepatic sulfatides, and decreased expression of hepatic CST. The clofibrate treatment attenuated kidney damage and hepatic oxidative stress while maintaining serum/hepatic sulfatide levels and hepatic CST content in the mice. Because clofibrate monotherapy without protein-overload treatment only minimally affected these hepatic parameters, the hepatic synthesis of sulfatides appeared to be strongly influenced by kidney dysfunction and subsequent oxidative stress. This study suggests that the crosstalk between kidney dysfunction and hepatic sulfatide metabolism is mediated by oxidative stress. These results should help to understand the phenomenon in patients with end-stage kidney disease.

• 2012-05-01

著者

• Hara Atsushi

  Department Of Astrophysics Nagoya University

• Hara Atsushi

  愛知県がんセンター研究所 分子病態学部

• Hara A

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

• Hara Atsushi

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

• Zhang Xiaowei

  Department Of Chemistry Wuhan University

• KYOGASHIMA Mamoru

  Division of Molecular Pathology, Aichi Cancer Center Research Institute

• Sugiyama Eiko

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

• Aoyama Toshifumi

  Department Of Biochemistry Shinshu University

• Tanaka Naoki

  Department Of Bio-molecular Engineering Kyoto Institute Of Technology

• Takahashi Kyoko

  Department Of Bioproduction Science Faculty Of Horticulture Chiba University

• Tanaka Naoki

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

• Kamijo Yuji

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

• Tadano-aritomi Keiko

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

• 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

• WANG Lixuan

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

• Wang Lixuan

  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

• Sugiyama Eiko

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

• Zhang Xiaowei

  Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, People's Republic of China

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