31 March | RESEARCH PAPERS A | admin
FLUORIDE-INDUCED APOPTOSIS IN HUMAN EPITHELIAL LUNG CELLS.
In the present study, possible mechanisms
involved in fluoride-induced apoptosis
in a human epithelial lung cell
line (A549) were examined.
FLUORIDE-INDUCED APOPTOSIS IN
HUMAN EPITHELIAL LUNG CELLS
( A549 CELLS )
ROLE OF DIFFERENT ‘G’ PROTEIN-LINKED
Refsnes M, Schwarze PE, Holme JA, Låg M.
Division of Environmental Medicine,
Norwegian Institute of Public Health,
PO Box 4404 Nydalen,
In the present study, possible mechanisms involved in fluoride-induced apoptosis in a human epithelial lung cell line (A549) were examined. Sodium fluoride (NaF) induced apoptosis in the A549 cells, with a maximum at 5-7.5 mM after 20 hours of exposure. The number of cells with plasma membrane damage (PI-positive cells) increased moderately up to 5 mM, but markedly at 7.5 mM. Deferoxamine (an Al3+ chelator) almost completely prevented these NaF-induced responses, which may suggest a role for G protein activation.
The apoptotic effect was partially reduced by the PKA inhibitor H89. NaF induced a weak but sustained increase in PKC activity, whereas the PKC activat or TPA induced a transient effect. TPA, which enhanced the NaF-induced PKC activity, was not apoptotic when added alone, but facilitated the NaF-induced apoptosis and the increase in PI-positive cells. PKC down regulation induced by TPA pretreatment almost completely prevented the NaF-induced apoptosis and the increase in PI-positive cells. Pretreatment with the PKC inhibitor GF109203X, which abolished the PKC activity after 3 hours, enhanced the NaF-induced apoptosis. KN93 (a CaM kinase II inhibitor) and W7 (a calmodulin inhibitor) seem to reduce the apoptotic effect of NaF, whereas BAPTA-AM (a Ca2+ chelator) was without effect. The tyrosine kinase inhibitor genistein also markedly reduced the NaF-induced apoptosis, whereas the PI-3 kinase inhibitor wortmannin augmented the response.
In conclusion, the present results suggest that NaF induces an apoptotic effect and an increase in PI-positive A549 cells via similar mechanisms, involving PKC, PKA, tyrosine kinase and Ca2+-linked enzymes, whereas PI-3 kinase seems to exert a counteracting effect.
PMID: 12723891 [PubMed – indexed for MEDLINE] Hum Exp Toxicol. 2003 Mar;22(3):111-23.