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Effect of Src Kinase inhibition on Cytochrome c, Smac/DIABLO and Apoptosis Inducing Factor (AIF) Following Cerebral Hypoxia-Ischemia in Newborn Piglets
Journal article   Open access   Peer reviewed

Effect of Src Kinase inhibition on Cytochrome c, Smac/DIABLO and Apoptosis Inducing Factor (AIF) Following Cerebral Hypoxia-Ischemia in Newborn Piglets

Panagiotis Kratimenos, Ioannis Koutroulis, Beamon Agarwal, Stamatios Theocharis and Maria Delivoria-Papadopoulos
Scientific reports, v 7(1), pp 16664-10
30 Nov 2017
DOI: https://doi.org/10.1038/s41598-017-16983-1
PMID: 29192254
Featured in Collection :   UN Sustainable Development Goals @ Drexel
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https://doi.org/10.1038/s41598-017-16983-1View
Published, Version of Record (VoR)CC BY V4.0,  Open

Abstract

Adenosine Triphosphate - metabolism Animals Apoptosis Apoptosis Inducing Factor - metabolism Apoptosis Regulatory Proteins - metabolism Biomarkers Caspases - genetics Caspases - metabolism Cerebral Cortex - blood supply Cerebral Cortex - metabolism Cerebral Cortex - pathology Cytochromes c - antagonists & inhibitors Cytochromes c - metabolism Hypoxia-Ischemia, Brain - etiology Hypoxia-Ischemia, Brain - metabolism Intracellular Signaling Peptides and Proteins - antagonists & inhibitors Intracellular Signaling Peptides and Proteins - metabolism Mitochondria - metabolism Models, Biological src-Family Kinases - metabolism Swine
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.

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UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Neurosciences
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