Abstract
Cell death inducing DNA fragmentation factor-alpha-like A (Cidea) is a member of cell death-inducing DFF45-like effector (CIDE) protein. The initial function of CIDE is the promotion of cell death and DNA fragmentation in mammalian cells. Cidea was recently reported to play critical roles in the development of hepatic steatosis. The purpose of present study is to determine the effect of chronic alcohol intake on Cidea expression in the livers of mice with alcoholic fatty liver disease. Cidea expression was significantly increased in the liver of alcohol-induced fatty liver mice. While, knockdown of Cidea caused lipid droplets numbers reduction. Next, we detected the activity of ALDH2 reduction and the concentration of serum acetaldehyde accumulation in our alcohol-induced fatty liver mice. Cidea expression was elevated in AML12 cells exposed to 100uM acetaldehyde. Interestingly, Dual-luciferase reporter gene assay showed that 100 uM acetaldehyde led to the activation of Cidea reporter gene plasmid which containing SRE element. What’s more, the knockdown of SREBP1c suppressed acetaldehyde-induced Cidea expression. Overall, our findings suggest that Cidea is highly associated with alcoholic fatty liver disease and Cidea expression is specifically induced by acetaldehyde, and this up-regulation is most likely mediated by SREBP1c.
Highlights
Alcohol consumption is a major risk factor for many chronic disease, especially alcoholic liver disease (ALD)[1]
Cell death inducing DNA fragmentation factor-alpha-like A (Cidea) is reported to be markedly up-regulated in ob/ob mouse livers[8,13], and its expression is induced by insulin in type 2 diabetic mouse livers[14,20]
Our findings showed that Cidea expression was highly increased in our alcohol-fed mice and alcohol-exposed AML12 cells
Summary
Alcohol consumption is a major risk factor for many chronic disease, especially alcoholic liver disease (ALD)[1]. Acetaldehyde, as a key toxin involved in alcohol-induced liver injury, increases triglycerides accumulation in recombinant HepG2 cells[15], enhances SREBP1c expression[16,17] and may impair the ability of PPARα to promote hepatic fat accumulation[18]. There are two important nuclear transcriptions, peroxisome proliferator-activated receptor-α(PPARα)[19] and sterol regulatory element-binding protein-1 (SREBP-1c)[16], are proved to be involved in alcohol-induced fatty liver. Abundant evidences have shown that Cidea promoter regions contain sterol-regulatory elements (SRE)[9,20], the expression of Cidea was induced in the presence of saturated fatty acids (FAs)[8] or insulin[20]. We formulate a hypothesis that acetaldehyde may promote the development of alcoholic fatty liver, and it is mediated by regulating Cidea expression. Cidea expression is induced by acetaldehyde, and this up-regulation is likely mediated by SREBP1c in hepatocytes
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