LEAD-EXPOSURE PROMOTES TRANSLOCATION OF PROTEIN-KINASE-C ACTIVITIES IN RAT CHOROID-PLEXUS IN-VITRO, BUT NOT IN-VIVO

Lead (Pb) exposure reportedly modulates PKC activity in brain endothel ial preparations, which may underlie Pb-induced damage at the blood-br ain barrier. Our previous work indicates that Pb accumulates in the ch oroid plexus and causes dysfunction of this blood-cerebrospinal fluid (CSF) barrier. The present studies were undertaken to test the hypothe sis that Pb in the choroid plexus may alter PKC activity and thus affe ct the functions of the blood-CSF barrier. When choroidal epithelial c ells in a primary culture were exposed to Pb (10 mu M in culture mediu m), the membrane-bound PKC activity increased by 5.2-fold, while the c ytosolic PKC activities decreased, an indication of the induction of P KC translocation by Pb. The effect of Pb on cellular PKC was concentra tion dependent in the range of 0.1-10 mu M. We further evaluated PKC a ctivity of the choroid plexus in rats chronically exposed to Pb in the drinking water (control, 50 or 250 mu g Pb/ml) for 30, 60, or 90 days . Two-way analysis of variance revealed a significant age-related decl ine of PKC activities in both cytosol and membrane of the choroid plex us. However, Pb treatment did not alter plexus PKC activities. In addi tion, we found that short-term, acute Pb exposure in rats did not sign ificantly change PKC activities nor did it affect the expression of PK C isoenzymes in the choroid plexus. Our results suggest that Pb exposu re may promote the translocation of PKC from cytosol to membrane in ra t blood-CSF barrier in vitro, but not in vivo. (C) 1998 Academic Press .