Activated Protein C and Thrombin Participate in Regulation of Astrocyte Functions

作者:Ivanova A E*; Gorbacheva L R; Strukova S M; Pinelis V G; Reiser G
来源:Biologicheskie Membrany, 2013, 30(5-6): 387-397.
DOI:10.7868/S0233475513050046

摘要

Anticoagulant protein C system is a multifunctional cofactor-dependent system. In addition to anticoagulant function, activated protein C (APC) also exhibits neuroprotective activity during hypoxia and stroke but there are no data concerning possible APC effects on astrocytes. In the present work we have studied an influence of APC and thrombin on the primary culture of rat astrocytes. It was found that thronibin in concentrations over 10 nM (1 unit/mL) induced a significant activation of cultured astrocytes resulting in reactive astrogliosis. Cultures exposed to thrombin for 24 h demonstrated a significant increase in the process of proliferation and increase in the expression of protein S100b. Thrombin at high concentrations produced visible changes in the astrocytes cytoskeleton, such as an increase in the amount of stress fibers in cultured cells. Moreover, thrombin apparently affected the astrocytes migration. Thus, the treatment of serum-starved astrocytes with thrombin resulted in a change in the uniformity of the cell monolayer and produced a formation of "free fields". APC prevented thrombin-induced proliferation of astrocytes and the expression of protein S100b, reducing the studied parameters to the control values. In addition, APC lessened thrombin-induced disorganization of the fibrils and the formation of the "free fields". The results reveal a new aspect of the protective action of APC that suppresses astrocyte activation induced by proinflammatory action of thrombin. This suggests a possible use of APC as a regulator of astrogliosis in pathological brain conditions.

  • 出版日期2013-12

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