Journal article
Augmented EGF receptor tyrosine kinase activity impairs vascular function by NADPH oxidase-dependent mechanism in type 2 diabetic mouse
Biochimica et biophysica acta. Molecular cell research, Vol.1853(10), pp.2404-2410
10/01/2015
DOI: 10.1016/j.bbamcr.2015.05.032
PMCID: PMC4855834
PMID: 26036345
Abstract
We previously determined that augmented EGFR tyrosine kinase (EGFRtk) impairs vascular function in type 2 diabetic mouse (TD2). Here we determined that EGFRtk causes vascular dysfunction through NADPH oxidase activity in TD2.
Mesenteric resistance arteries (MRA) from C57/BL6 and db(-)/db(-) mice were mounted in a wired myograph and pre-incubated for 1 h with either EGFRtk inhibitor (AG1478) or exogenous EGF. The inhibition of EGFRtIc did not affect the contractile response to phenylephrine-(PE) and thromboxane-(U46619) or endothelium-dependent relaxation (EDR) to acetylcholine in MRA from control group. However, in TD2 mice, AG1478 reduced the contractile response to U46619, improved vasodilatation and reduced p22phox-NADPH expression, but had no effect on the contractile response to PE. The incubation of MRA with exogenous EGF potentiated the contractile response to PE in MRA from control and diabetic mice. However, EGF impaired the EDR and potentiated the vasoconstriction to 1346619 only in the control group. Interestingly, NADPH oxidase inhibition in the presence of EGF restored the normal contraction to PE and improved the EDR but had no effect on the potentiated contraction to U46619. Vascular function improvement was associated with the rescue of eNOS and Alct and reduction in phosphorylated Rho-kinase, NOX4 mRNA levels, and NADPH oxidase activity. MRA from p47(phox-/-) incubated with EGF potentiated the contraction to 1346619 but had no effect to PE or ACh responses.
The present study provides evidence that augmented EGFRtk impairs vascular function by NADPH oxidase-dependent mechanism. Therefore, EGFRtk and oxidative stress should be potential targets to treat vascular dysfunction in TD2. (C) 2015 Elsevier B.V. All rights reserved.
Details
- Title: Subtitle
- Augmented EGF receptor tyrosine kinase activity impairs vascular function by NADPH oxidase-dependent mechanism in type 2 diabetic mouse
- Creators
- Modar Kassan - Eastern Virginia Medical SchoolKarima Ait-Aissa - Eastern Virginia Medical SchoolMaha Ali - Eastern Virginia Medical SchoolMohamed Trebak - Assiut UniversityKhalid Matrougui - Eastern Virginia Medical School
- Resource Type
- Journal article
- Publication Details
- Biochimica et biophysica acta. Molecular cell research, Vol.1853(10), pp.2404-2410
- DOI
- 10.1016/j.bbamcr.2015.05.032
- PMID
- 26036345
- PMCID
- PMC4855834
- NLM abbreviation
- Biochim Biophys Acta Mol Cell Res
- ISSN
- 0167-4889
- eISSN
- 1879-2596
- Publisher
- Elsevier
- Number of pages
- 7
- Grant note
- R01HL097111 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) HL095566; HL097111 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 10/01/2015
- Academic Unit
- Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984359576702771
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