Premium
Peroxisome proliferator‐activated receptor γ ligands stimulate myeloid differentiation and lipogenensis in human leukemia NB4 cells
Author(s) -
Yasugi Etsuko,
Horiuchi Akiko,
Uemura Isao,
Okuma Emiko,
Nakatsu Masami,
Saeki Kumiko,
Kamisaka Yasushi,
Kagechika Hiroyuki,
Yasuda Kazuki,
Yuo Akira
Publication year - 2006
Publication title -
development, growth and differentiation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.864
H-Index - 66
eISSN - 1440-169X
pISSN - 0012-1592
DOI - 10.1111/j.1440-169x.2006.00855.x
Subject(s) - adipocyte , peroxisome proliferator activated receptor , cellular differentiation , lipogenesis , retinoic acid , ciglitazone , microbiology and biotechnology , retinoid x receptor , chemistry , peroxisome , myeloid , receptor , transcription factor , nuclear receptor , biology , biochemistry , adipose tissue , cancer research , gene
Peroxisome proliferator‐activated receptor γ (PPARγ) plays a central role in adipocyte and macrophage differentiation. Pioglitazone (Actos, AD4833), an antidiabetic drug, and 15‐deoxy‐Δ 12,14 ‐prostaglandin J2 (PGJ2) have recently been identified as synthetic and natural ligands for PPARγ, respectively. In this study, we examined the effects of PPARγ ligands on differentiation and lipogenesis in promyelocytic leukemia NB4 cells, in which PPARγ protein was expressed and ligand‐stimulated PPARγ‐specific transcription of adipocyte fatty‐acid binding protein was confirmed. Treatment with PPARγ ligand (AD4833 or PGJ2) alone markedly suppressed proliferation but did not induce differentiation. The combined treatment of the cells with PPARγ ligand and all‐trans retinoic acid (ATRA) synergistically induced myelocytic differentiation, as determined by nitroblue tetrazolium reducing ability and cell morphology. During these processes of differentiation, we observed marked accumulation of lipid droplets in the cytoplasm. The cellular triacylglycerol levels increased 2.7‐fold after treatment with the inducers. Simultaneously, BODIPY‐fatty acid was incorporated into the cytosol and concentrated in lipid droplets. The biosynthesis of triacylglycerol‐containing BODIPY‐fatty acids was increased twofold in differentiated cells. These findings clearly demonstrate that treatment with PPARγ ligands not only induced differentiation but also stimulated lipogenesis in NB4 cells, indicating a close association between differentiation and lipogenesis in PPARγ‐stimulated human myeloid cells.