Document Type
Journal Article
Publication Date
11-30-2017
Journal
Scientific Reports
Volume
7
Issue
1
DOI
10.1038/s41598-017-16983-1
Abstract
We have previously shown that cerebral Hypoxia-ischemia (HI) results in activation of Src kinase in the newborn piglet brain. We investigated the regulatory mechanism by which the pre-apoptotic proteins translocate from mitochondria to the cytosol during HI through the Src kinase. Newborn piglets were divided into 3 groups (n = 5/group): normoxic (Nx), HI and HI pre-treated with Src kinase inhibitor PP2 (PP2 + HI). Brain tissue HI was verified by neuropathological analysis and by Adenosine Triphosphate (ATP) and Phosphocreatine (PCr) levels. We used western blots, immunohistochemistry, H&E and biochemical enzyme assays to determine the role of Src kinase on mitochondrial membrane apoptotic protein trafficking. HI resulted in decreased ATP and PCr levels, neuropathological changes and increased levels of cytochrome c, Smac/DIABLO and AIF in the cytosol while their levels were decreased in mitochondria compared to Nx. PP2 decreased the cytosolic levels of pre-apoptotic proteins, attenuated the neuropathological changes and apoptosis and decreased the HI-induced increased activity of caspase-3. Our data suggest that Src kinase may represent a potential target that could interrupt the enzymatic activation of the caspase dependent cell death pathway.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
APA Citation
Kratimenos, P., Koutroulis, I., Agarwal, B., Theocharis, S., & Delivoria-Papadopoulos, M. (2017). Effect of Src Kinase Inhibition on Cytochrome c, Smac/DIABLO and Apoptosis Inducing Factor (AIF) Following Cerebral Hypoxia-Ischemia in Newborn Piglets.. Scientific Reports, 7 (1). http://dx.doi.org/10.1038/s41598-017-16983-1
Peer Reviewed
1
Open Access
1
Comments
Reproduced with permission of Macmillan Publishers Ltd. Scientific Reports