Down-regulation of apolipoprotein M expression is mediated by phosphatidylinositol 3-kinase in HepG2 cells.
Apolipoprotein M (apoM) is a novel apolipoprotein present mostly in high-density lipoprotein (HDL) in human plasma. In the present study, we demonstrate that insulin, insulin-like growth factor I (IGF-I), and IGF-I potential peptide (IGF-IPP) significantly inhibits apoM expression, in a dose- and a time-dependent manner, in the human hepatoma cell line, HepG2 cells. Insulin-induced down-regulation of apoM was blocked by AG1024 (a specific insulin receptor inhibitor) and LY294002 (a phosphatidylinositol 3-kinase (PI3K) inhibitor), which indicates that it is mediated via the activation of PI3K pathway. In contrast, PD98059 (a MAP kinase inhibitor) did not influence insulin-induced down-regulation of apoM expression, and activation of neither PPAR-alpha agonist (GW7647) nor PPAR-gamma agonist (GW1929) influences apoM expression in HepG2 cells, which indicates that regulation of apoM expression is not related to the activation of PPAR-alpha and PPAR-gamma in hepatic cells, whereas, both PPAR-alpha and PPAR-gamma agonists could inhibit apoB expression. Moreover, in the present study, we demonstrated that PPAR beta/delta agonist (GW501516) could inhibit both apoM and apoB expression in the HepG2 cells. In conclusion, this study shows that apoM expression is regulated by PI3-kinase in HepG2-cells.
Xu
Ning
N
Section of Clinical Chemistry & Pharmacology, Department of Laboratory Medicine, Lunds University, S-221 85 Lund, Sweden. ning.xu@med.lu.se
Ahrén
Bo
B
Jiang
Jingting
J
Nilsson-Ehle
Peter
P
D001053:Apolipoproteins / Q000235:genetics*; D001055:Apolipoproteins B / Q000235:genetics; D000075243:Apolipoproteins M; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D054834:Lipocalins; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
C400523:APOM protein, human; D001053:Apolipoproteins; D001055:Apolipoproteins B; D000075243:Apolipoproteins M; D007328:Insulin; D054834:Lipocalins; D047492:Peroxisome Proliferator-Activated Receptors; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases