Angelis Dimitrios, Delivoria-Papadopoulos Maria
aDepartment of Pediatrics, Texas Tech University Health Sciences Center at the Permian Basin, Odessa, Texas bDepartment of Pediatrics, Drexel University and St Christopher's Hospital for Children, Philadelphia, Pennsylvania, USA.
Neuroreport. 2017 Aug 16;28(12):770-773. doi: 10.1097/WNR.0000000000000835.
Caspase-2 has features of both initiator and effector caspases. Previously, we have shown that brain hypoxia-induced production of caspases 1, 3, 8, and 9 is Src kinase mediated, a nonreceptor intracellular family of kinases. The present study tests the hypothesis that hypoxia results in increased expression of caspase-2 and this effect is mediated by Src kinase. Two to three days old newborn piglets were subjected to normoxia, hypoxia (Hx, FiO2 7%), and Src kinase inhibition (using PP2, 1 mg/kg, intravenous), followed by 30 min of acute hypoxia (Hx+PP2). ATP and phosphocreatine were determined biochemically to verify energy molecule depletion in the hypoxic groups. The cytosolic brain function was isolated and a western blot analysis was carried out using an antibody specific for the caspase-2. The immune-complex band density was expressed as OD/mm. Caspase-2 expression was increased two-fold in the Hx group. After Src kinase inhibition followed by hypoxia, caspase-2 expression was similar to normoxia levels. We conclude that hypoxia results in increased expression of caspase-2 protein in the cytosolic fraction of the cerebral cortex of the newborn piglets. This increase is mediated by Src kinase.
半胱天冬酶 -2 兼具起始半胱天冬酶和效应半胱天冬酶的特征。此前，我们已经表明，脑缺氧诱导的半胱天冬酶 1、3、8 和 9 的产生是由Src激酶介导的，Src激酶是一种非受体细胞内激酶家族。本研究检验了以下假设：缺氧会导致半胱天冬酶 -2 的表达增加，且这种效应由Src激酶介导。对2至3日龄的新生仔猪进行常氧、缺氧（Hx，吸入氧分数为7%）和Src激酶抑制（使用PP2，1mg/kg，静脉注射）处理，随后进行30分钟的急性缺氧（Hx + PP2）。通过生化方法测定三磷酸腺苷（ATP）和磷酸肌酸，以验证缺氧组中能量分子的消耗情况。分离出大脑的胞质功能部分，并使用针对半胱天冬酶 -2 的特异性抗体进行蛋白质免疫印迹分析。免疫复合物条带密度以光密度值（OD）/毫米表示。在缺氧组中，半胱天冬酶 -2 的表达增加了两倍。在Src激酶抑制后再进行缺氧处理，半胱天冬酶 -2 的表达与常氧水平相似。我们得出结论，缺氧会导致新生仔猪大脑皮质胞质部分中半胱天冬酶 -2 蛋白的表达增加。这种增加是由Src激酶介导的。
