Activated protein C is the regulator of the NF-κB activity under the conditions of glutamate toxicity

Abstract

Activated protein C (APC) is one of the key proteinases of hemostasis exhibiting anti-coagulant, anti-inflammatory, and protective functions. In the present work, the anti-apoptotic effect of the proteinase on the glutamate toxicity model in cultured hippocampal neurons has been discovered. It is demonstrated that high concentrations of glutamate induce translocation of p65 subunit of transcription factor NF-κB into the nucleus, while low concentrations of APC prevent this effect of the neurotransmitter. Moreover, helenalin, a specific inhibitor of NF-κBp65, similar to APC, increased survival of neurons under toxic conditions. Using specific blocking antibodies, we have revealed that APC via its own receptor (endothelial protein C receptor) and protease activated receptor 1 (PAR1) inhibits glutamate-induced activation of transcription factor NF-κB. Thus, APC in low concentrations protects hippocampal neurons from glutamate-induced death through a receptor-dependent regulation of the activity of p65 subunit of transcription factor NF-κB.