| Nox4-derived reactive oxygen species mediate cardiomyocyte injury in early type 1 diabetes. | |
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MedLine Citation:
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PMID: 22031600 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Oxidative stress contributes to diabetic cardiomyopathy. This study explored the role of the NADPH oxidase Nox4 as a source of reactive oxygen species (ROS) involved in the development of diabetic cardiomyopathy. Phosphorothioated antisense (AS) or sense (S) oligonucleotides for Nox4 were administered for 2 wk to rats made diabetic by streptozotocin. NADPH oxidase activity, ROS generation, and the expression of Nox4, but Nox1 or Nox2, were increased in left ventricular tissue of the diabetic rats. Expression of molecular markers of hypertrophy and myofibrosis including fibronectin, collagen, α-smooth muscle actin, and β-myosin heavy chain were also increased. These parameters were attenuated by the administration of AS but not S Nox4. Moreover, the impairment of contractility observed in diabetic rats was prevented in AS- but not S-treated animals. Exposure of cultured cardiac myocytes to 25 mM glucose [high glucose (HG)] increased NADPH oxidase activity, the expression of Nox4, and molecular markers of cardiac injury. These effects of HG were prevented in cells infected with adenoviral vector containing a dominant negative form of Nox4. This study provides strong evidence that Nox4 is an important source of ROS in the left ventricle and that Nox4-derived ROS contribute to cardiomyopathy at early stages of type 1 diabetes. |
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Authors:
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Rita M Maalouf; Assaad A Eid; Yves C Gorin; Karen Block; Gladys Patricia Escobar; Steven Bailey; Hanna E Abboud |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-10-26 |
Journal Detail:
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Title: American journal of physiology. Cell physiology Volume: 302 ISSN: 1522-1563 ISO Abbreviation: Am. J. Physiol., Cell Physiol. Publication Date: 2012 Feb |
Date Detail:
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Created Date: 2012-01-25 Completed Date: 2012-03-25 Revised Date: 2012-05-15 |
Medline Journal Info:
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Nlm Unique ID: 100901225 Medline TA: Am J Physiol Cell Physiol Country: United States |
Other Details:
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Languages: eng Pagination: C597-604 Citation Subset: IM |
Affiliation:
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Dept. of Medicine, Division of Cardiology, Univ. of Texas Health Science Center, San Antonio, TX 78229-3900, USA. rita.maalouf@ndu.edu.lb |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Actins
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biosynthesis Animals Cells, Cultured Collagen / biosynthesis Diabetes Mellitus, Experimental / complications, metabolism Diabetes Mellitus, Type 1 / complications, metabolism* Diabetic Cardiomyopathies / metabolism*, pathology Fibronectins / biosynthesis Glucose / pharmacology Heart Ventricles / metabolism* Humans Male Membrane Glycoproteins / biosynthesis Myocytes, Cardiac / metabolism*, pathology* NADH, NADPH Oxidoreductases / biosynthesis NADPH Oxidase / biosynthesis, metabolism* Oligonucleotides, Antisense / pharmacology Oxidative Stress Rats Rats, Sprague-Dawley Reactive Oxygen Species / metabolism* Ventricular Myosins / biosynthesis |
| Grant Support | |
ID/Acronym/Agency:
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R01 DK079996/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Actins; 0/Fibronectins; 0/Membrane Glycoproteins; 0/Oligonucleotides, Antisense; 0/Reactive Oxygen Species; 50-99-7/Glucose; 9007-34-5/Collagen; EC 1.6.-/Cybb protein, rat; EC 1.6.-/NADH, NADPH Oxidoreductases; EC 1.6.-/Nox4 protein, rat; EC 1.6.3.1/NADPH Oxidase; EC 1.6.99.-/NADPH oxidase 1; EC 3.6.1.-/Ventricular Myosins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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