| Impairment of gastric nitrergic and NRF2 system in apolipoprotein E knockout mice. | |
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MedLine Citation:
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PMID: 22302246 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND AND AIM: Gastric motility dysfunction is most commonly seen in diabetic and idiopathic gastroparesis patients. Recently we reported that impaired nitrergic relaxation and a reduced NO (nitric oxide) bioavailability were responsible for gastric motility dysfunction in diabetic female rats. One of the main factors involved in the inactivation of the nitrergic system is oxidative stress commonly seen in diabetic patients. Hyperlipidemia may also be one of the detrimental causes for impaired gastric motility associated with diabetes. In the current study, we investigated whether apolipoprotein E knockout mice (ApoE-KO), an oxidative stress animal model with a hyperlipidemia burden, also displays an impaired nitrergic system. To test this, nitrergic relaxation (AUC/mg tissue) was measured at 2 Hz through electric field stimulation using gastric pyloric strips prepared from C57BL WT or ApoE-KO female mice. Protein expression was determined by Western blots. RESULTS: Nitrergic relaxation was reduced in gastric strips from ApoE-KO versus WT mice. Protein levels of nNOS (neuronal nitric oxide synthase), GCH-1 (GTP cyclohydrolase 1), Nrf2 (nuclear factor E-2 related factor 2) and GCSc (glutamate-cysteine ligase catalytic) were also reduced in ApoE-KO compared to controls, with no significant change in GCSm (glutamate-cysteine ligase modifier) and HO-1 (heme oxygenase 1). The activities of DHFR (dihydrofolate reductase) and antioxidant enzymes were also reduced in ApoE-KO mice. CONCLUSIONS: This novel study is the first to reveal that a deficiency in ApoE impairs gastric motility functions, and that hyperlipidemia and the suppression of selective antioxidants may be an underlying mechanism for this pathological change. |
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Authors:
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Kalpana Ravella; Hong Yang; Pandu R R Gangula |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Digestive diseases and sciences Volume: 57 ISSN: 1573-2568 ISO Abbreviation: Dig. Dis. Sci. Publication Date: 2012 Jun |
Date Detail:
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Created Date: 2012-07-11 Completed Date: 2012-07-31 Revised Date: 2013-04-04 |
Medline Journal Info:
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Nlm Unique ID: 7902782 Medline TA: Dig Dis Sci Country: United States |
Other Details:
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Languages: eng Pagination: 1504-9 Citation Subset: AIM; IM |
Affiliation:
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Department of Physiology, Meharry Medical College, Nashville, TN 37208, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Analysis of Variance Animals Apolipoproteins E / deficiency*, metabolism Blotting, Western Disease Models, Animal Female Gastric Mucosa / metabolism, pathology Hyperlipidemias / metabolism, physiopathology Mice Mice, Inbred C57BL Mice, Knockout NF-E2-Related Factor 2 / metabolism* Nitrergic Neurons / physiology Nitric Oxide / metabolism Nitric Oxide Synthase Type I / genetics, metabolism* Oxidative Stress / physiology* Pylorus / metabolism*, physiopathology Random Allocation Sensitivity and Specificity Stomach / metabolism, physiopathology Superoxide Dismutase / genetics, metabolism Tetrahydrofolate Dehydrogenase / analysis, metabolism Tissue Culture Techniques |
| Grant Support | |
ID/Acronym/Agency:
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G12RR03032/RR/NCRR NIH HHS; P60DK020593/DK/NIDDK NIH HHS; R21 DK076704/DK/NIDDK NIH HHS; R21DK076704/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Apolipoproteins E; 0/NF-E2-Related Factor 2; 10102-43-9/Nitric Oxide; EC 1.14.13.39/Nitric Oxide Synthase Type I; EC 1.14.13.39/Nos1 protein, mouse; EC 1.15.1.-/superoxide dismutase 1; EC 1.15.1.1/Superoxide Dismutase; EC 1.5.1.-/dihydrofolate reductase type II; EC 1.5.1.3/Tetrahydrofolate Dehydrogenase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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