Nuclear inositol lipid cycle and differentiation.
Previous investigations from our laboratory and others have shown the existence of an autonomous intranuclear inositide cycle endowed with conventional lipid kinases and PLC which in PC12 pheochromocytoma cells, human osteosarcoma SaOS-2 cells, rat liver and Swiss 3T3 cells is the isoform beta 1, which in the latter cells is activated upon IGF-I stimulation. The behavior of the nuclear inositol lipid cycle has been investigated in nuclei of Friend erythroleukemia cells. These nuclei possess both lipid kinases and PLC. The cycle upon treatment with differentiating agents (i.e., DMSO and tiazofurin) is characterized by an accumulation of polyphosphoinositides and a decrease of DAG due to down-regulation of a specific PLC. Indeed, even if both beta 1 and gamma 1 isoforms are present in these nuclei, when Friend cells undergo terminal erythroid differentiation only the PLC beta 1 isoform is down-regulated as shown by immunochemical and immunocytochemical analysis, by direct determination of enzymatic activity and in the presence of neutralizing monoclonal antibodies as well as by Northern blot for PLC beta 1 message, whilst the amount of PLC gamma 1 and its activity are unaffected by erythroid differentiation. In conclusion, the presence of a specific nuclear PLC whose activity and expression are down-regulated during differentiation of erythroleukemia cells points out a role for nuclear phosphoinositide signalling in the processes of cell differentiation and hints at the nuclear PLC beta 1 as an important step of the cycle in relation to the erythroid differentiative commitment of murine erythroleukemia cells.
Cocco
L
L
Institute of Human Anatomy, University of Bologna, Italy.
Martelli
A M
AM
Capitani
S
S
Maraldi
N M
NM
Mazzotti
G
G
Barnabei
O
O
Gilmour
R S
RS
Manzoli
F A
FA
D000818:Animals; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism*; D004075:Diglycerides / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D004915:Leukemia, Erythroblastic, Acute; D051379:Mice; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D012254:Ribavirin / Q000031:analogs & derivatives / Q000494:pharmacology; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D004075:Diglycerides; D018129:Phosphatidylinositol Phosphates; D012254:Ribavirin; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases; C033706:tiazofurin; D004121:Dimethyl Sulfoxide