Activated protein C and thrombin participate in the regulation of astrocyte functions

Abstract

Protein C anticoagulant system is a multifunctional cofactor-dependent system. In addition to anticoagulant function, activated protein C (APC) also exhibits neuroprotective activity in hypoxia and stroke, but there are no data on potential effects of APC on astrocytes. In the present work we have studied the influence of APC and thrombin on rat astrocytes in primary culture. It was found that thrombin at concentrations above 10 nM (1 U/mL) induced significant activation in the cultured astrocytes resulting in reactive astrogliosis. The cultures exposed to thrombin for 24 h demonstrated a significant increase in proliferation and the S100b protein expression. Thrombin at high concentrations produced visible changes in the cytoskeleton of astrocytes, in particular, an increase in the number of stress fibers in the cultured cells. Moreover, thrombin apparently affected astrocyte migration. Thus, the treatment of serum-starved astrocytes with thrombin resulted in changes in cell monolayer uniformity and formation of “free fields”. APC prevented thrombin-induced proliferation of astrocytes and the S100b protein expression, reducing the parameters under study to the control values. In addition, APC reduced thrombin-induced disorganization of fibrils and formation of “free fields”. The results have demonstrated a new aspect of the protective effect of APC, which suppresses astrocyte activation induced by the proinflammatory effect of thrombin. It suggests a potential application of APC as a regulator of astrogliosis in pathological brain conditions.