The Influence of β-Arrestin-2 Gene Knockout in Mice on Survival of Cultured Astrocytes Exposed to Thrombin and on the Cerebral Thrombosis Aftereffects In Vivo
Thrombin is a multifunctional serine protease that attracts the attention of many researchers in particular in connection with a wide range of its effects in the nervous tissue. It is known that the main thrombin receptor is a protease-activated type 1 receptor, the functional activity of which is associated with adapter protein β‑arrestin-2. Here we assessed a potential involvement of β-arrestin-2 in the thrombin toxicity both in vitro and in vivo using gene knockout mice. It was found that thrombin induced dose-dependent cell death of cultured β-arrestin-2<sup>–/–</sup> astrocytes 48 h after the exposure. In contrast, thrombin did not exert any effect on the survival of astrocytes from wild-type animals. The in vivo study showed that β-arrestin-2 gene knockout did not alter the severity of the focal photoinduced cerebral ischemia effects, which could involve additional cell types and molecular mechanisms in the nervous tissue damage. Our findings demonstrate for the first time the necessity of β-arrestin-2 for survival of mouse astrocytes under the toxic action of thrombin. However, further studies at the CNS level are required to determine the key targets of this protease in each cell types of the nervous tissue and to clarify the role of β-arrestin signaling in neuroprotection.