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Chronic ethanol consumption decreases serum sulfatide levels by suppressing hepatic cerebroside sulfotransferase expression in mice

  • Molecular Toxicology
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Abstract

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.

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Abbreviations

ALD:

Alcoholic liver disease

ALT:

Alanine aminotransferase

ApoB:

Apolipoprotein B

ARSA:

Arylsulfatase A

AST:

Aspartate aminotransferase

CAT:

Catalase

CST:

Cerebroside sulfotransferase

CVD:

Cardiovascular disease

CYBB:

NADPH oxidase 2

GALC:

Galactosylceramidase

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

GPX:

Glutathione peroxidase

HDL-C:

High-density lipoprotein cholesterol

LDL-C:

Low-density lipoprotein cholesterol

FABP:

Fatty acid-binding protein

HNE:

Hydroxynonenal

LS:

Lysosulfatides

MALDI-TOF MS:

Matrix-assisted laser desorption ionization–time-of-flight mass spectrometry

MDA:

Malondialdehyde

MTTP:

Microsomal triglyceride transfer protein

NCF:

Neutrophil cytosolic factor

PCR:

Polymerase chain reaction

PPAR:

Peroxisome proliferator-activated receptor

ROS:

Reactive oxygen species

SCP2:

Sterol carrier protein 2

SD:

Standard deviation

SOD:

Superoxide dismutase

TF:

Tissue factor

TG:

Triglyceride

UGT:

UDP-glucuronosyltransferase

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The authors declare that they have no conflicts of interest.

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Authors and Affiliations

  1. Department of Metabolic Regulation, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan

    Hiroki Kanbe, Yuji Kamijo, Takero Nakajima, Naoki Tanaka, Eiko Sugiyama, Atsushi Hara & Toshifumi Aoyama

  2. Basic Discovery Research R & D, Kissei Pharmaceutical Co., Ltd., 4365-1 Kashiwabara, Hotaka, Azumino, 399-8304, Japan

    Hiroki Kanbe

  3. Department of Nephrology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan

    Yuji Kamijo

  4. Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20852, USA

    Naoki Tanaka, Zhong-Ze Fang & Frank J. Gonzalez

  5. Department of Nutritional Science, Nagano Prefectural College, Nagano, 380-8525, Japan

    Eiko Sugiyama

  6. Department of Histology and Embryology, Hebei Medical University, Shijiazhuang, 050017, People’s Republic of China

    Lixuan Wang

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  1. Hiroki Kanbe
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  2. Yuji Kamijo
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  3. Takero Nakajima
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  10. Toshifumi Aoyama
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Correspondence to Naoki Tanaka.

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Kanbe, H., Kamijo, Y., Nakajima, T. et al. Chronic ethanol consumption decreases serum sulfatide levels by suppressing hepatic cerebroside sulfotransferase expression in mice. Arch Toxicol 88, 367–379 (2014). https://doi.org/10.1007/s00204-013-1132-3

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  • DOI: https://doi.org/10.1007/s00204-013-1132-3

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