Peroxisome proliferator-activated receptor gamma ligands stimulate myeloid differentiation and lipogenensis in human leukemia NB4 cells.
Peroxisome proliferator-activated receptor gamma (PPARgamma) plays a central role in adipocyte and macrophage differentiation. Pioglitazone (Actos, AD4833), an antidiabetic drug, and 15-deoxy-Delta(12,14)-prostaglandin J2 (PGJ2) have recently been identified as synthetic and natural ligands for PPARgamma, respectively. In this study, we examined the effects of PPARgamma ligands on differentiation and lipogenesis in promyelocytic leukemia NB4 cells, in which PPARgamma protein was expressed and ligand-stimulated PPARgamma-specific transcription of adipocyte fatty-acid binding protein was confirmed. Treatment with PPARgamma ligand (AD4833 or PGJ2) alone markedly suppressed proliferation but did not induce differentiation. The combined treatment of the cells with PPARgamma 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 PPARgamma ligands not only induced differentiation but also stimulated lipogenesis in NB4 cells, indicating a close association between differentiation and lipogenesis in PPARgamma-stimulated human myeloid cells.
Department of Hematology, Research Institute, International Medical Center of Japan, 1-21-1, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan. e-yasugi@umin.ac.jp
Etsuko
E
Yasugi
Akiko
A
Horiuchi
Isao
I
Uemura
Emiko
E
Okuma
Masami
M
Nakatsu
Kumiko
K
Saeki
Yasushi
Y
Kamisaka
Hiroyuki
H
Kagechika
Kazuki
K
Yasuda
Akira
A
Yuo
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000813:Anilides / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D050556:Fatty Acid-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008055:Lipids / Q000502:physiology*; D022423:Myeloid Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D047495:PPAR gamma / Q000187:drug effects / Q000502:physiology*; D000077205:Pioglitazone; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D045162:Thiazolidinediones / Q000494:pharmacology*; D014212:Tretinoin / Q000494:pharmacology; D014280:Triglycerides / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
C097240:15-deoxy-delta(12,14)-prostaglandin J2; C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D001565:Benzoates; D001713:Biphenyl Compounds; D050556:Fatty Acid-Binding Proteins; D008024:Ligands; D008055:Lipids; D047495:PPAR gamma; D045162:Thiazolidinediones; D014280:Triglycerides; C438269:diazepinylbenzoic acid; D014212:Tretinoin; D015230:Prostaglandin D2; D000077205:Pioglitazone