Cide-a and Cide-c are induced in the progression of hepatic steatosis and inhibited by eicosapentaenoic acid.
Cide-a and Cide-c belong to the cell death-inducing DNA fragmentation factor-alpha-like effector family. Recent evidences suggest that these proteins may be involved in lipid accumulation in liver and adipose tissues. We confirmed that in the high-fat/high-sucrose diet-induced murine model of hepatic steatosis, the expression levels of the Cide-a and Cide-c genes were markedly and time-dependently increased, but returned to normal levels following improvement of hepatic steatosis by eicosapentaenoic acid (EPA) administration. Levels of expression of the Cide-a and Cide-c genes correlated well with plasma ALT. EPA inhibited the promoter activity of the Cide-a gene in vitro. Sterol regulatory element-binding protein-1 (SREBP-1) markedly enhanced the promoter activity of Cide-a, and EPA inhibited the expression of Cide-a mRNA. SREBP-1 and EPA did not affect those of Cide-c. These findings indicate that Cide-a and Cide-c are closely involved in the progression of hepatic steatosis, and that EPA inhibits Cide-a gene expression through SREBP-1 regulation.
Jinno
Yasutaka
Y
Development Research, Pharmaceutical Research Center, Mochida Pharmaceutical Co., Ltd., Shizuoka 412-8524, Japan.
Nakakuki
Masanori
M
Sato
Ayumi
A
Kawano
Hiroyuki
H
Notsu
Tatsuto
T
Mizuguchi
Kiyoshi
K
Shimano
Hitoshi
H
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis*; D004032:Diet / Q000009:adverse effects; D004041:Dietary Fats / Q000009:adverse effects / Q000494:pharmacology; D004195:Disease Models, Animal; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D005234:Fatty Liver / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000378:metabolism*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D013395:Sucrose / Q000009:adverse effects / Q000494:pharmacology; D013549:Sweetening Agents / Q000009:adverse effects / Q000494:pharmacology
D051017:Apoptosis Regulatory Proteins; C112510:Cidea protein, mouse; D004041:Dietary Fats; D011506:Proteins; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D013549:Sweetening Agents; C525805:fat-specific protein 27, mouse; D013395:Sucrose; D015118:Eicosapentaenoic Acid