Lipid droplet formation in human myeloid NB4 cells stimulated by all trans retinoic acid and granulocyte colony-stimulating factor: possible involvement of peroxisome proliferator-activated receptor gamma.
All trans retinoic acid (ATRA), a differentiation inducer for human myeloid NB4 cells, induced accumulation of lipid droplet as determined by positivity of Nile Red and Oil Red O in this cell line. Granulocyte colony-stimulating factor (G-CSF), although not having detectable effect by itself, exerted the additive effects on lipid droplet formation in NB4 cells when combined with ATRA. mRNA analysis for peroxisome proliferator-activated receptors (PPARs) revealed the initial transient downregulation followed by upregulation of the transcript for PPARgamma2, a master molecule for adipogenesis, and upregulation of PPARalpha. BADGE, a synthetic antagonist for PPARgamma, potently inhibited lipid droplet formation in NB4 cells stimulated by ATRA and/or G-CSF, but not the functional differentiation of the cells by ATRA and/or G-CSF. These results suggest that ATRA and G-CSF induce lipid droplet formation via certain PPARgamma-mediated specific mechanisms in human myeloid NB4 cells during functional differentiation.
Inazawa
Yuko
Y
Department of Hematology, Research Institute, International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan.
Nakatsu
Masami
M
Yasugi
Etsuko
E
Saeki
Kumiko
K
Yuo
Akira
A
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D002479:Inclusion Bodies / Q000737:chemistry / Q000378:metabolism; D050356:Lipid Metabolism; D022423:Myeloid Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology*
D000970:Antineoplastic Agents; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D014212:Tretinoin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor