Journal article
Mechanism of activation of caspase-9 and caspase-3 during hypoxia in the cerebral cortex of newborn piglets: the role of nuclear Ca2+ -influx
Neurochemical research, v 32(3), pp 401-405
Mar 2007
PMID: 17268855
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
In previous studies, we have shown that cerebral hypoxia results in increased activity of caspase-9, the initiator caspase, and caspase-3, the executioner of programmed cell death. We have also shown that cerebral hypoxia results in high affinity Ca2+-ATPase-dependent increase in nuclear Ca2+ -influx in the cerebral cortex of newborn piglets. The present study tests the hypothesis that inhibiting nuclear Ca2+ -influx by pretreatment with clonidine, an inhibitor of high affinity Ca2+ -ATPase, will prevent the hypoxia-induced increase in caspase-9 and caspase-3 activity in the cerebral cortex of newborn piglets. Thirteen newborn piglets were divided into three groups, normoxic (Nx, n=4), hypoxic (Hx, n=4), and hypoxic treated with clonidine (100 mg/kg) (Hx-Cl, n=5). Anesthetized, ventilated animals were exposed to an FiO2 of 0.21 (Nx) or 0.07 (Hx) for 60 min. Cerebral tissue hypoxia was documented biochemically by determining levels of ATP and phosphocreatine (PCr). Caspase-9 and -3 activity were determined spectrofluoro-metrically using specific fluorogenic synthetic substrates. ATP (micromoles/g brain) was 4.6 +/- 0.3 in Nx, 1.7 +/- 0.4 in Hx (P < 0.05 vs. Nx), and 1.5 +/- 0.2 in Hx-Cl (P < 0.05 vs. Nx). PCr (micromoles/g brain) was 3.6 +/- 0.4 in Nx, 1.1 +/- 0.3 in Hx (P < 0.05 vs. Nx), and 1.0 +/- 0.2 in Hx-Cl (P < 0.05 vs. Nx). Caspase-9 activity (nmoles/mg protein/h) was 0.548 +/- 0.0642 in Nx and increased to 0.808 +/- 0.080 (P < 0.05 vs. Nx and Hx-Cl) in the Hx and 0.562 +/- 0.050 in the Hx-Cl group (p = NS vs. Nx). Caspase-3 activity (nmoles/mg protein/h) was 22.0 +/- 1.3 in Nx and 32 +/- 6.3 in Hx (P < 0.05 vs. Nx) and 18.8 +/- 3.2 in the Hx-Cl group (P < 0.05 vs. Hx). The data demonstrate that clonidine administration prior to hypoxia prevents the hypoxia-induced increase in the activity of caspase-9 and caspase-3. We conclude that the high afinity Ca2+ -ATPase-dependent increased nuclear Ca2+ during hypoxia results in increased caspase-9 and caspase-3 activity.
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Details
- Title
- Mechanism of activation of caspase-9 and caspase-3 during hypoxia in the cerebral cortex of newborn piglets: the role of nuclear Ca2+ -influx
- Creators
- Maria Delivoria-Papadopoulos - Drexel UniversityOm P Mishra - Drexel University
- Publication Details
- Neurochemical research, v 32(3), pp 401-405
- Publisher
- Springer Nature
- Grant note
- HD-38079 / NICHD NIH HHS HD-20337 / NICHD NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pediatrics
- Web of Science ID
- WOS:000244315200003
- Scopus ID
- 2-s2.0-33847167553
- Other Identifier
- 991019168654504721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Biochemistry & Molecular Biology
- Neurosciences