Journal article
Temporal Changes in Caspase-1 and Caspase-8 Activities Following Brain Hypoxia With and Without Src kinase Inhibition in a Piglet Animal Model
Neurochemical research, v 40(11), pp 2270-2279
Nov 2015
PMID: 26342830
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The Src family kinases are a family of intracellular, non-receptor tyrosine kinases that are involved in a variety of cellular functions including the regulation of inflammation and apoptosis after brain hypoxia. Caspase-1 (C1) activates IL-1β through the formation of complex structures, the inflammasomes, while caspase-8 (C8) is part of the extrinsic apoptotic pathway. C8 has been found to directly activate the production of IL-1β. Previously, we observed that C1 and IL-1β are increased in the acute phase after hypoxia in the brain of piglets, but they follow a different pattern long term, with C1 remaining activated throughout the period of observation, while IL-1β returning to baseline at 15 days. Src kinase inhibition ameliorated the activation of C1 and IL-1β early, but did not appear to have any effect long term. Prompted by these findings, we assessed the changes that occur over time (1 h and 15 days) in C1 and C8 activities after brain hypoxia as well as the effect of pretreatment with a Src kinase inhibitor, PP2 on these biochemical markers. Enzymatic activities were determined by spectrophotometry with measurements of C1 and C8 in each cytosolic brain sample (N = 4 in each group). We found that C1 and C8 activities increase in the acute phase following hypoxia in the brain of newborn piglets, with C8 relatively more than C1 (C8/C1 ratio increased from 2:1 as baseline to 3:1 in hypoxia). Fifteen days after hypoxia C8/C1 ratio decreased to about 1:1. In piglets that were pretreated with a Src kinase selective inhibitor (PP2) and then subjected to hypoxia, the C8/C1 ratio early increase was not observed. Immediately after hypoxia C8 and C1 follow a similar pattern of increase while long term this appears to dissociate. We propose that following this experimental methodology, the previously observed IL-1β production after hypoxia might be associated with C8 rather than C1 and that Src kinase is involved in the above process.
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Details
- Title
- Temporal Changes in Caspase-1 and Caspase-8 Activities Following Brain Hypoxia With and Without Src kinase Inhibition in a Piglet Animal Model
- Creators
- Dimitrios Angelis - St. Christopher's Hospital for ChildrenTania D Fontánez Nieves - Department of Pediatrics, Drexel University and St. Christopher's Hospital for Children, Philadelphia, PA, USAMaria Delivoria-Papadopoulos - St. Christopher's Hospital for Children
- Publication Details
- Neurochemical research, v 40(11), pp 2270-2279
- Publisher
- Springer Nature
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pediatrics
- Web of Science ID
- WOS:000365085500012
- Scopus ID
- 2-s2.0-84947043303
- Other Identifier
- 991019168695304721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Neurosciences