TY - JOUR
T1 - Effects of Src kinase inhibition on expression of pro-caspase-2 after brain hypoxia in a piglet animal model
AU - Angelis, DImitrios
AU - Delivoria-Papadopoulos, Maria
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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, FiO 2 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 2. 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.
AB - 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, FiO 2 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 2. 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.
KW - Apoptosis
KW - caspase-2
KW - hypoxic ischemic brain injury
KW - newborn piglet
KW - PP2
KW - Src kinase
UR - http://www.scopus.com/inward/record.url?scp=85021390425&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85021390425&partnerID=8YFLogxK
U2 - 10.1097/WNR.0000000000000835
DO - 10.1097/WNR.0000000000000835
M3 - Article
C2 - 28658050
AN - SCOPUS:85021390425
SN - 0959-4965
VL - 28
SP - 770
EP - 773
JO - NeuroReport
JF - NeuroReport
IS - 12
ER -