Chronic ethanol consumption decreases serum sulfatide levels by suppressing hepatic cerebroside sulfotransferase expression in mice.
Epidemiological studies demonstrate a possible relationship between chronic ethanol drinking and thrombotic diseases, such as myocardial infarction and stroke. However, the precise mechanism for this association remains unclear. Sulfatides are endogenous glycosphingolipids composed of ceramide, galactose, and sulfate, known to have anti-thrombotic properties. Low (0.5 g/kg/day), middle (1.5 g/kg/day), and high (3.0 g/kg/day) doses of ethanol were administered for 21 days intraperitoneally to female wild-type mice, and serum/liver sulfatide levels were measured. No significant changes in cholesterol and triglycerides were seen in serum and liver by ethanol treatment. However, serum/liver sulfatide levels were significantly decreased by middle- and high-dose ethanol treatment, likely due to downregulation of hepatic cerebroside sulfotransferase (CST) levels. Marked decreases in the expression of catalase and superoxide dismutases and ensuing increases in lipid peroxides were also observed in the livers of mice with middle- and high-dose ethanol treatment, suggesting the association between the suppression of hepatic CST expression and enhancement of oxidative stress. Furthermore, serum levels of tissue factor, a typical pro-coagulant molecule, were significantly increased in the mice with middle- and high-dose ethanol treatment showing decreases in serum sulfatide levels. Collectively, these results demonstrate that chronic ethanol consumption reduces serum sulfatide levels by increasing oxidative stress and decreasing the expression of CST in the liver. These findings could provide a mechanism by which chronic ethanol drinking increases thrombotic events.
Department of Metabolic Regulation, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan.
Hiroki
H
Kanbe
Yuji
Y
Kamijo
Takero
T
Nakajima
Naoki
N
Tanaka
Eiko
E
Sugiyama
Lixuan
L
Wang
Zhong-Ze
ZZ
Fang
Atsushi
A
Hara
Frank J
FJ
Gonzalez
Toshifumi
T
Aoyama
D000437:Alcoholism / Q000097:blood; D000818:Animals; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D051147:Ganglioside Galactosyltransferase / Q000235:genetics; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D018384:Oxidative Stress / Q000187:drug effects; D013433:Sulfoglycosphingolipids / Q000097:blood* / Q000378:metabolism; D015238:Sulfotransferases / Q000378:metabolism*; D013925:Thromboplastin / Q000378:metabolism
D013433:Sulfoglycosphingolipids; D000431:Ethanol; D013925:Thromboplastin; C511214:Ugt8a protein, mouse; D051147:Ganglioside Galactosyltransferase; D015238:Sulfotransferases; C020556:galactosylceramide sulfotransferase