| Carbonylation of myosin heavy chains in rat heart during diabetes. | |
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MedLine Citation:
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PMID: 20359464 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cardiac inotropy progressively declines during diabetes mellitus. To date, the molecular mechanisms underlying this defect remain incompletely characterized. This study tests the hypothesis that ventricular myosin heavy chains (MHC) undergo carbonylation by reactive carbonyl species (RCS) during diabetes and these modifications contribute to the inotropic decline. Male Sprague-Dawley rats were injected with streptozotocin (STZ). Fourteen days later the animals were divided into two groups: one group was treated with the RCS blocker aminoguanidine for 6 weeks, while the other group received no treatment. After 8 weeks of diabetes, cardiac ejection fraction, fractional shortening, left ventricular pressure development (+dP/dt) and myocyte shortening were decreased by 9%, 16%, 34% and 18%, respectively. Ca(2+)- and Mg(2+)-actomyosin ATPase activities and peak actomyosin syneresis were also reduced by 35%, 28%, and 72%. MHC-alpha to MHC-beta ratio was 12:88. Mass spectrometry and Western blots revealed the presence of carbonyl adducts on MHC-alpha and MHC-beta. Aminoguanidine treatment did not alter MHC composition, but it blunted formation of carbonyl adducts and decreases in actomyosin Ca(2+)-sensitive ATPase activity, syneresis, myocyte shortening, cardiac ejection fraction, fractional shortening and +dP/dt induced by diabetes. From these new data it can be concluded that in addition to isozyme switching, modification of MHC by RCS also contributes to the inotropic decline seen during diabetes. |
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Authors:
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Chun-Hong Shao; George J Rozanski; Ryoji Nagai; Frank E Stockdale; Kaushik P Patel; Mu Wang; Jaipaul Singh; William G Mayhan; Keshore R Bidasee |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-03-30 |
Journal Detail:
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Title: Biochemical pharmacology Volume: 80 ISSN: 1873-2968 ISO Abbreviation: Biochem. Pharmacol. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-05-10 Completed Date: 2010-05-26 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 0101032 Medline TA: Biochem Pharmacol Country: England |
Other Details:
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Languages: eng Pagination: 205-17 Citation Subset: IM |
Copyright Information:
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2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5800, United States. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Diabetes Mellitus, Experimental / metabolism* Enzyme Inhibitors / pharmacology Guanidines / pharmacology Heart Diseases / metabolism* Heart Ventricles / chemistry, metabolism Hemodynamics / drug effects Male Myocardial Contraction / drug effects, physiology* Myocytes, Cardiac / drug effects, pathology, physiology Myosin Heavy Chains / chemistry, metabolism* Organometallic Compounds / chemistry, metabolism* Oxidative Stress Protein Carbonylation* Rats Rats, Sprague-Dawley Streptozocin |
| Grant Support | |
ID/Acronym/Agency:
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AA 01128/AA/NIAAA NIH HHS; HL 090657/HL/NHLBI NIH HHS; HL-066446/HL/NHLBI NIH HHS; HL085061/HL/NHLBI NIH HHS; NS-39751/NS/NINDS NIH HHS; R01 HL085061-02/HL/NHLBI NIH HHS; R01 HL085061-03/HL/NHLBI NIH HHS; R01 HL085061-04/HL/NHLBI NIH HHS; R01 NS039751-01/NS/NINDS NIH HHS; R01 NS039751-02/NS/NINDS NIH HHS; R01 NS039751-03/NS/NINDS NIH HHS; R01 NS039751-04/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 0/Guanidines; 0/Myosin Heavy Chains; 0/Organometallic Compounds; 18883-66-4/Streptozocin; 79-17-4/pimagedine |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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