Journal article
Hypoxia-induced Activation of Epidermal Growth Factor Receptor (EGFR) Kinase in the Cerebral Cortex of Newborn Piglets: The Role of Nitric Oxide
Neurochemical research, v 35(9), pp 1471-1477
01 Sep 2010
PMID: 20532621
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The present study aims to investigate the mechanism of EGFR kinase activation during hypoxia and tests the hypothesis that hypoxia-induced increased activation of EGFR kinase in the cerebral cortical membrane fraction of newborn piglets is mediated by nitric oxide (NO) derived from neuronal nitric oxide synthase (nNOS). Fifteen newborn piglets were divided into normoxic (Nx, n = 5), hypoxic (Hx, n = 5) and hypoxic-treated with nNOS inhibitor (Hx-nNOSi, n = 5). Hypoxia was induced by an FiO2 of 0.07 for 60 min. nNOS inhibitor I (selectivity [2,500 vs. endothelial NOS, eNOS, and[500 vs. inducible NOS, iNOS) was administered (0.4 mg/kg, i.v.) 30 min prior to hypoxia. EGFR kinase tyrosine phosphorylation at Tyr1173, an index of activation of EGFR kinase, was determined by Western blot analysis using an anti-phospho (pTyr 1173)-EGFR kinase antibody. Protein bands were analyzed by imaging densitometry and expressed as absorbance (OD 9 mm 2). EGFR kinase activity was determined radiochemically using immunopurified enzyme. EGFR kinase activity was expressed as pmols/mg protein/hr. Density of phosphor (pTyr 1173)-EGFR kinase (OD 9 mm 2) was 60.2 +/- 9.8 in Nx, 177.0 +/- 26.9 in Hx (P<0.05 vs. Nx) and 79.9 +/- 15.7 in Hx-nNOSi (P<0.05 vs. Hx, P = NS vs. Nx). Activity of EGFR kinase (pmoles/mg protein/hr) was 4,603 +/- 155 in Nx, 8,493 +/- 427 in Hx (P<0.05 vs. Nx) and 4,516 +/- 104 in Hx-nNOSi (P<0.05 vs. Hx, P = NS vs. Nx). Pretreatment with nNOS inhibitor prevented the hypoxia-induced increased phosphorylation and increased activity of EGFR kinase. We conclude that the mechanism of hypoxia-induced increased activation of EGFR kinase is mediated by nNOS-derived NO.
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Details
- Title
- Hypoxia-induced Activation of Epidermal Growth Factor Receptor (EGFR) Kinase in the Cerebral Cortex of Newborn Piglets: The Role of Nitric Oxide
- Creators
- Om Prakash Mishra - Drexel UniversityQazi M. Ashraf - Drexel UniversityMaria Delivoria-Papadopoulos - Drexel University
- Publication Details
- Neurochemical research, v 35(9), pp 1471-1477
- Publisher
- Springer Nature
- Number of pages
- 7
- Grant note
- HD-38079; HD-20337 / National Institute of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01HD038079 / EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH &HUMAN DEVELOPMENT; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pediatrics
- Web of Science ID
- WOS:000280729700019
- Scopus ID
- 2-s2.0-77957831547
- Other Identifier
- 991019168293804721
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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