Interleukin 1 alpha stimulates nuclear phospholipase C in human osteosarcoma SaOS-2 cells.
Interleukin 1 (IL-1) is one of the most potent stimulators of bone resorption. However, the early biochemical events elicited by IL-1 receptor binding are not fully understood. Here we show that in human osteosarcoma SaOS-2 cells the treatment with IL-1 alpha is able to evoke a rapid and transient increase of nuclear phospholipase C (PLC) activity. A parallel decrease of nuclear phosphatidylinositol monophosphate and phosphatidylinositol bisphosphate is observed. All these events are strictly confined to the nuclear compartment without affecting the cytoplasmatic inositol lipid pool. In addition we show that by Western blot analysis with specific monoclonal antibodies the PLC gamma is located both in the cytoplasm and in the nucleus, while PLC beta appears exclusively localized in the nucleus. Moreover, the increase of PLC activity in response to IL-1 alpha is completely neutralized by monoclonal antibody against the beta-form. While confirming the existence of an autonomous nuclear phosphoinositide signaling system, our data clearly indicate that in SaOS-2 cells one of the earliest events following IL-1 alpha treatment is the breakdown of nuclear phosphatidylinositol monophosphate and phosphatidylinositol bisphosphate because of the activation of a specific nuclear PLC isoform.
Marmiroli
S
S
Istituto di Citomorfologia Normale e Patologica, Consiglio Nazionale delle Richerche, Bologna, Italy.
Ognibene
A
A
Bavelloni
A
A
Cinti
C
C
Cocco
L
L
Maraldi
N M
NM
D002467:Cell Nucleus / Q000201:enzymology*; D004789:Enzyme Activation; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism; D012516:Osteosarcoma / Q000201:enzymology*; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000378:metabolism*
D007375:Interleukin-1; D007527:Isoenzymes; D010738:Type C Phospholipases