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.
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Dongqing
D
Guo
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Xiaowei
X
Zhang
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Qin
Q
Li
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Lei
L
Qian
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Jiajia
J
Xu
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Ming
M
Lu
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Xihan
X
Hu
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Ming
M
Zhu
Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover NH 03755, USA.
Catherine C Y
CC
Chang
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.|College of Life Sciences, The Institute for Advanced Studies, Wuhan University, Wuhan 430072, China.
Baoliang
B
Song
Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover NH 03755, USA.
Tayuan
T
Chang
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Ying
Y
Xiong
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China blli@sibcb.ac.cn.
Boliang
B
Li
D002460:Cell Line; D002788:Cholesterol Esters / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000201:enzymology*; D008074:Lipoproteins / Q000378:metabolism*; D002785:Sterol O-Acyltransferase / Q000235:genetics*; D014212:Tretinoin / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D000097587:Sterol O-Acyltransferase 2
D002788:Cholesterol Esters; D008074:Lipoproteins; D002785:Sterol O-Acyltransferase; D014212:Tretinoin; D014409:Tumor Necrosis Factor-alpha; D000097587:Sterol O-Acyltransferase 2
ACAT2 expression; ACAT2 isoform-selective inhibitor PPPA; C/EBPs; NBD22-steryl ester; human leukocytes; lipoprotein excretion
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