title: Attenuation of kidney injuries maintains serum sulfatide levels dependent on hepatic synthetic ability: a possible involvement of oxidative stress.
abstract: 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.
authors.affiliation: Department of Metabolic Regulation, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, Matsumoto, Japan.
authors.forename: Xiaona
authors.initials: X
authors.lastname: Sheng
authors.forename: Takero
authors.initials: T
authors.lastname: Nakajima
authors.forename: Lixuan
authors.initials: L
authors.lastname: Wang
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Zhang
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kamijo
authors.forename: Kyoko
authors.initials: K
authors.lastname: Takahashi
authors.forename: Naoki
authors.initials: N
authors.lastname: Tanaka
authors.forename: Eiko
authors.initials: E
authors.lastname: Sugiyama
authors.forename: Mamoru
authors.initials: M
authors.lastname: Kyogashima
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Aoyama
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hara
mesh_terms: D000208:Acute Disease; D000818:Animals; D002994:Clofibrate / Q000494:pharmacology; D004195:Disease Models, Animal; D004336:Drug Antagonism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D000960:Hypolipidemic Agents / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D057507:Mice, 129 Strain; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D012710:Serum Albumin, Bovine / Q000633:toxicity; D013433:Sulfoglycosphingolipids / Q000097:blood*; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000960:Hypolipidemic Agents; D013433:Sulfoglycosphingolipids; D012710:Serum Albumin, Bovine; D015238:Sulfotransferases; C020556:galactosylceramide sulfotransferase; D002994:Clofibrate