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Inorganic phosphate inhibits growth of human osteosarcoma U2OS cells via adenylate cyclase/cAMP pathway
Author(s) -
Naviglio Silvio,
Spina Annamaria,
Chiosi Emilio,
Fusco Anna,
Illiano Fausto,
Pagano Mario,
Romano Maria,
Senatore Giovanna,
Sorrentino Annunziata,
Sorvillo Luca,
Illiano Gennaro
Publication year - 2006
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.20892
Subject(s) - forskolin , ibmx , adenylate kinase , intracellular , cell culture , cyclase , microbiology and biotechnology , cell growth , signal transduction , phosphate , chemistry , growth inhibition , biology , biochemistry , enzyme , genetics
In order to elucidate how phosphate regulates cellular functions, we investigated the effects of inorganic phosphate (Pi) on adenylate cyclase (AC)/cyclic AMP (cAMP) axis. Here we describe that Pi treatment of human osteosarcoma U2OS cells results in a decrease of both intracellular cAMP levels and AC activity, and in a cell growth inhibition. The phosphate‐triggered effects observed in U2OS cells are not a widespread phenomenon regarding all cell lines, since other cell lines screened respond differently to parallel Pi treatments. In U2OS cell line, the AC activity/cAMP downregulation is accompanied by significant variations in the levels of some membrane proteins belonging to the AC system. Remarkably, the above effects are blunted by pharmacological inhibition of sodium‐dependent phosphate transport. Moreover, 8‐Br‐cAMP and other cAMP‐elevating agents, such as IBMX and forskolin, interestingly, prevent the cell growth inhibition in response to phosphate. Our results enforce the increasing evidences of phosphate as a signaling molecule, identifying in U2OS cell line the AC/cAMP axis, as a novel‐signaling pathway modulated by phosphate to ultimately affect cell growth. J. Cell. Biochem. © 2006 Wiley‐Liss, Inc.