The ACAT2 expression of human leukocytes is responsible for the excretion of lipoproteins containing cholesteryl/steryl esters.
Acyl-coenzymeA:cholesterol acyltransferase 2 (ACAT2) is abundantly expressed in intestine and fetal liver of healthy human. Our previous studies have shown that in monocytic cells the low-level expression of human ACAT2 gene with specific CpG-hypomethylated promoter is regulated by the CCAAT/enhancer binding protein (C/EBP) transcription factors. In this study, we further report that the ACAT2 gene expression is attributable to the C/EBPs in the human leukocytes and correlated with the excretion of fluorescent lipoproteins containing the ACAT2-catalyzed NBD22-steryl esters. Moreover, this lipoprotein excretion can be inhibited by the ACAT2 isoform-selective inhibitor pyripyropene A (PPPA) in a dose-dependent manner, and employed to determine the half maximum inhibitory concentration (IC50) values of PPPA. Significantly, it is found that the differentiation-inducing factor all-trans retinoic acid, but not the proinflammatory cytokine tumor necrosis factor-α, enhances this ACAT2-dependent lipoprotein excretion. These data demonstrate that the ACAT2 expression of human leukocytes is responsible for the excretion of lipoproteins containing cholesteryl/steryl esters (CE/SE), and suggest that the excretion of lipoproteins containing the ACAT2-catalyzed CS/SE may avoid cytotoxicity through decreasing the excess intracellular cholesterols/sterols (especially various oxysterols), which is essential for the action of the human leukocytes.
['Guo|Dongqing|D|', 'Zhang|Xiaowei|X|', 'Li|Qin|Q|', 'Qian|Lei|L|', 'Xu|Jiajia|J|', 'Lu|Ming|M|', 'Hu|Xihan|X|', 'Zhu|Ming|M|', 'Chang|Catherine C Y|CC|', 'Song|Baoliang|B|', 'Chang|Tayuan|T|', 'Xiong|Ying|Y|', 'Li|Boliang|B|']
D002460:Cell Line D002788:Cholesterol Esters D015870:Gene Expression D006801:Humans D007962:Leukocytes D008074:Lipoproteins D002785:Sterol O-Acyltransferase D014212:Tretinoin D014409:Tumor Necrosis Factor-alpha
ACAT2 expression human leukocytes C/EBPs NBD22-steryl ester lipoprotein excretion ACAT2 isoform-selective inhibitor PPPA