title: Transient activation of protein kinase C contributes to fluoride-induced  apoptosis of rat erythrocytes.
abstract: Role of PKC in fluoride-induced apoptosis of rat erythrocytes was studied in vitro and in vivo. Treatment of erythrocytes with 5 mM NaF for 1–24 h caused progressive accumulation of cytosolic Ca2+ and PS exposure at outer membrane surface. After 1 h, these processes were suppressed by PKC inhibitors staurosporine, GF 109203X and chelerythrine, but increased by PKC activator PMA. Following 24 h, NaF-induced Ca2+ uptake and PS externalization were partly prevented by PMA or staurosporine, but not by GF 109293X and chelerythrine. Application of PP inhibitor OA augmented NaF-induced cell responses within 1 h, but not after 24 h. Incubation of erythrocytes with 0.1–10 mM NaF for 1 h produced a dose-dependent PKCa translocation from cytosol to membranes with appearance of active PKM fragment. 24 h NaF exposure led to complete loss of cytosolic PKCa and proteolysis of membrane PKCa. Besides, NaF weakly stimulated membrane PKCf, although its subcellular distribution was not altered. Thus, transient PKCa activation/translocation positively contributes to NaF-induced apoptosis in vitro. Consumption of 2–20 ppm fluoride by the rats for 12 months also induced dose-dependent PKCa translocation to membranes and activation of membrane PKCf, what indicates that PKC stimulation is an important physiological mechanism of fluoride toxicity.
authors.forename: Natalia I
authors.initials: NI
authors.lastname: Agalakova
authors.forename: Gennadii P
authors.initials: GP
authors.lastname: Gusev
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012969:Sodium Fluoride / Q000633:toxicity*
chemical_list: D007527:Isoenzymes; D012969:Sodium Fluoride; D011493:Protein Kinase C; D002118:Calcium