Role of Protein Kinases on NF-κB Activation and Cell Death in Bovine Cerebral Endothelial Cells

Role of Protein Kinases on NF-κB Activation and Cell Death in Bovine Cerebral Endothelial Cells

<P> Nuclear factor κB (NF-κB) activation is modulated by various protein kinases. Activation of NF-κB is known to be important in the regulation of cell viability. The present study investigated the effect of inhibitors of protein tyrosine kinase (PTK), protein kinase C (PKC) and protein kinase A (PKA) on NF-κB activity and the viability of bovine cerebral endothelial cells (BCECs). In serum-deprivation-induced BCEC death, low doses of TNFα showed a protective effect. TNFα induced NF-κB activation within 4 h in serum-deprivation. PTK inhibitors (herbimycin A and genistein) and PKC inhibitor (calphostin C) prevented NF-κB activation stimulated by TNFα. Likewise, these inhibitors prevented the protective effect of TNFα. In contrast to TNFα-stimulated NF-κB activity, basal NF-κB activity of BCECs in media containing serum was suppressed only by calphostin C, but not by herbimycin A. As well BCEC death was also induced only by calphostin C in serum-condition. H 89, a PKA inhibitor, did not affect the basal and TNFα- stimulated NF-κB activities and the protective effect of TNFα on cell death. These data suggest that modulation of NF-κB activation could be a possible mechanism for regulating cell viability by protein kinases in BCECs.