Interleukin-1 alpha induces variations of the intranuclear amount of phosphatidylinositol 4,5-bisphosphate and phospholipase C beta 1 in human osteosarcoma Saos-2 cells.
Some key elements of signal transduction have been identified within the nucleus and demonstrated to be responsive to specific agonists in numerous cell types. In particular, mitogenic stimuli have been reported to induce a transient increase of the nuclear phospholipase C beta 1 activity, causing the release of inositide-derived second messengers, whereas differentiating stimuli induced a decrease of the enzyme activity and an increase of nuclear phosphatidylinositol 4,5-bisphosphate (PIP2). Recently, we reported evidence, in human osteosarcoma Saos-2 cell lines, on the presence of specific nuclear phospholipase C isoforms and on the activation of phospholipase C beta 1 in the nucleus following the exposure to interleukin-1 alpha. In this study we report immunocytochemical ultrastructural evidence on quantitative variations of PIP2 and phospholipase C beta 1 amounts in the nucleus of Saos-2 cells at different times of exposure to interleukin-1 alpha. After short periods of culture in the presence of the agonist, the intranuclear amount of PIP2 is decreased, while a translocation of phospholipase C beta 1 occurs from the cytoplasm to the nucleus, in correspondence with the increased hydrolyzing activity of the enzyme. After longer periods of incubation with interleukin-1 alpha, on the other hand, the intranuclear amount of PIP2 is restored to initial level, while the amount of phospholipase C beta 1 is increased both at the nuclear and cytoplasmic level, when its activation is no longer effective. The results, compared with those obtained in other cell types responsive to given agonists, account for a cell-specific modulation of signal transduction based on polyphosphoinositide breakdown at the nuclear level.
Zini
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N
Istituto di Citomorfologia Normale e Patologica, C.N.R., Chieti-Bologna, Sezione di Bologna c/o I.O.R., Italy.
Sabatelli
P
P
Faenza
I
I
Ognibene
A
A
Maraldi
N M
NM
D001859:Bone Neoplasms / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000494:pharmacology*; D007527:Isoenzymes / Q000032:analysis*; D016253:Microscopy, Immunoelectron; D012516:Osteosarcoma / Q000378:metabolism*; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000032:analysis*; D054799:Phospholipase C beta; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000032:analysis*
D007375:Interleukin-1; D007527:Isoenzymes; D019269:Phosphatidylinositol 4,5-Diphosphate; D010738:Type C Phospholipases; C518033:PLCB1 protein, human; D054799:Phospholipase C beta