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Journal article
Nitric-oxide Synthase-2 Linkage to Focal Adhesion Kinase in Neutrophils Influences Enzyme Activity and beta(2) Integrin Function
The Journal of biological chemistry, v 288(7), pp 4810-4818
15 Feb 2013
PMID: 23297409
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
This investigation was to elucidate the basis for augmentation of nitric-oxide synthesis in neutrophils exposed to hyperbaric oxygen. Hyperoxia increases synthesis of reactive species leading to S-nitrosylation of beta-actin, which causes temporary inhibition of beta(2) integrin adherence. Impaired beta(2) integrin function and actin S-nitrosylation do not occur in neutrophils from mice lacking type-2 nitric-oxide synthase (iNOS) or when incubated with 1400W, an iNOS inhibitor. Similarly, effects of hyperoxia were abrogated in cells depleted of focal adhesion kinase (FAK) by treatment with small inhibitory RNA and those exposed to a specific FAK inhibitor concurrent with hyperoxia. Nitric oxide production doubles within 10 min exposure to hyperoxia but declines to approximately half-maximum production over an additional 10 min. Elevated nitric oxide production did not occur after FAK depletion or inhibition, or when filamentous actin formation was inhibited by cytochalasin D. Intracellular content of iNOS triples over the course of a 45-min exposure to hyperoxia and iNOS dimers increase in a commensurate fashion. Confocal microscopy and immunoprecipitation demonstrated that co-localization/linkage of FAK, iNOS, and filamentous actin increased within 15 min exposure to hyperoxia but then decreased below the control level. Using isolated enzymes in ex vivo preparations an association between iNOS and filamentous actin mediated by FAK could be demonstrated and complex formation was impeded when actin was S-nitrosylated. We conclude that iNOS activity is increased by an FAK-mediated association with actin filaments but peak nitric oxide production is transient due to actin S-nitrosylation during exposure to hyperoxia.
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Details
- Title
- Nitric-oxide Synthase-2 Linkage to Focal Adhesion Kinase in Neutrophils Influences Enzyme Activity and beta(2) Integrin Function
- Creators
- Stephen R. Thom - University of PennsylvaniaVeena M. Bhopale - Institute for Environmental Medicine, University of Pennsylvania Medical Center and School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, Pennsylvania 19104Tatyana N. Milovanova - Institute for Environmental Medicine, University of Pennsylvania Medical Center and School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, Pennsylvania 19104Ming Yang - Institute for Environmental Medicine, University of Pennsylvania Medical Center and School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, Pennsylvania 19104Marina Bogush - Institute for Environmental Medicine, University of Pennsylvania Medical Center and School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, Pennsylvania 19104Donald G. Buerk - Drexel University
- Publication Details
- The Journal of biological chemistry, v 288(7), pp 4810-4818
- Publisher
- Amer Soc Biochemistry Molecular Biology Inc
- Number of pages
- 9
- Grant note
- Office of Naval Research
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000315340400030
- Scopus ID
- 2-s2.0-84874088795
- Other Identifier
- 991019168069904721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology