| Mechanisms related to NO-induced motility in differentiated rat aortic smooth muscle cells. | |
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MedLine Citation:
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PMID: 21037226 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Nitric oxide (NO) is thought to play an important role as an inhibitor of vascular cell proliferation, motility, and neointima formation. This effect is mediated, in part, via the upregulation of protein tyrosine phosphatase (PTP)1B. Conversely, studies have reported that in presumably hyperinsulinemic mice fed a high-fat diet, NO enhances vascular remodeling, whereas a deficit of NO attenuates vascular remodeling. We have reported that in differentiated cultured smooth muscle cells treated with insulin, NO induces a motogenic effect that is dependent on Src homology-2 domain PTP 2 (SHP2) upregulation. In the present study, we describe novel mechanisms relevant to the motogenic effect of NO. Treatment of cultured cells with the selective angiontensin type 1 receptor antagonist losartan, but not with the selective angiotensin type 2 receptor antagonist PD-123319, blocked the comotogenic capacity of NO and insulin. Insulin and NO increased the secretion of ANG II into the culture media by 2- and 2.5-fold (P < 0.05), respectively, whereas treatment of cells with ANG II uncovered the motogenic effect of NO (1.4-fold above control, P < 0.05) and decreased the levels of PTP1B to 45% of control (P < 0.05). Suppression of PTP1B function was sufficient to uncover the motogenic effect of NO. The capacity of insulin to suppress PTP1B activity was blocked by losartan, implicating ANG II function in mediating this effect. Both insulin and ANG II induced the upregulation of phosphatidyl inositol 3-kinase (PI3K)-δ by two- to threefold (P < 0.05), and this effect was both necessary and sufficient to uncover NO-induced motogenesis. Finally, suppression of PTP1B function potentiated, whereas overexpression of PTP1B inhibited, SHP2-induced motogenesis. These results support the hypothesis that the comotogenic effect of insulin and NO occurs via an ANG II-mediated effect involving the suppression of PTP1B and upregulation of PI3K-δ and SHP2. |
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Authors:
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Qinghua Pu; Daming Zhuang; Shalini Thakran; Aviv Hassid |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-10-29 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 300 ISSN: 1522-1539 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-01-04 Completed Date: 2011-01-28 Revised Date: 2012-01-02 |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H101-8 Citation Subset: IM |
Affiliation:
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Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Analysis of Variance Angiotensin II / metabolism Angiotensin II Type 1 Receptor Blockers / pharmacology Angiotensin II Type 2 Receptor Blockers / pharmacology Animals Aorta, Thoracic / cytology, drug effects, metabolism* Cell Movement / drug effects, physiology* Cells, Cultured Enzyme-Linked Immunosorbent Assay Imidazoles / pharmacology Insulin / metabolism, pharmacology* Losartan / pharmacology Male Muscle, Smooth, Vascular / cytology, drug effects, metabolism* Myocytes, Smooth Muscle / cytology, drug effects, metabolism* Nitric Oxide / metabolism, pharmacology* Phosphatidylinositol 3-Kinases / metabolism Protein Tyrosine Phosphatase, Non-Receptor Type 11 / metabolism Pyridines / pharmacology RNA, Small Interfering Rats Rats, Sprague-Dawley Up-Regulation |
| Grant Support | |
ID/Acronym/Agency:
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HL-63886/HL/NHLBI NIH HHS; HL-72902/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Angiotensin II Type 1 Receptor Blockers; 0/Angiotensin II Type 2 Receptor Blockers; 0/Imidazoles; 0/Insulin; 0/Pyridines; 0/RNA, Small Interfering; 10102-43-9/Nitric Oxide; 11128-99-7/Angiotensin II; 114798-26-4/Losartan; 130663-39-7/PD 123319; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 3.1.3.48/Protein Tyrosine Phosphatase, Non-Receptor Type 11 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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