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pubmed-article:21760968pubmed:dateCreated2011-7-15lld:pubmed
pubmed-article:21760968pubmed:abstractTextWe tested the hypothesis that exercise ameliorates contractile dysfunction by interfering with homocysteine - ?2-adrenergic receptor (AR) interactions, inducing ?2-adrenergic response and Gs (stimulatory G adenylyl cyclase dependent protein kinase), and lowering homocysteine level in diabetes. The effect of homocysteine on ?2-AR was determined by (a) scoring the ?2-AR in the cardiomyocytes treated with high dose of homocysteine using flow cytometry, and (b) co-localizing homocysteine with Gs (an inducer of ?2-AR) in the cardiomyocytes obtained from C57BL/ 6J (WT) and db/ db mice using confocal microscopy. The effect of exercise on the protein-protein interactions of homocysteine and ?2-AR in diabetes was evaluated by co-immunoprecipitation in the four groups of db/db mice: (1) sedentary, (2) treated with salbutamol (a ?2-AR agonist), (3) swimming exercise, and (4) swimming + salbutamol treatment. The effect of exercise on ?2-AR was determined by RT-PCR and Western blotting while cardiac dysfunction was assessed by echocardiography, and contractility and calcium transient of cardiomyocytes from the above four groups. The results revealed that elevated level of homocysteine decreases the number of ?2-AR and inhibits Gs in diabetes. However, exercise mitigates the interactions of homocysteine with ?2-AR and induces ?2-AR. Exercise also ameliorates cardiac dysfunction by enhancing the calcium transient of cardiomyocytes. To our knowledge, this is the first report showing mechanism of homocysteine mediated attenuation of ?2-AR response in diabetes and effect of exercise on homocysteine - ?2-AR interactions.lld:pubmed
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pubmed-article:21760968pubmed:authorpubmed-author:TyagiSuresh...lld:pubmed
pubmed-article:21760968pubmed:authorpubmed-author:JoshuaIrving...lld:pubmed
pubmed-article:21760968pubmed:authorpubmed-author:MishraParas...lld:pubmed
pubmed-article:21760968pubmed:authorpubmed-author:MetreveliNair...lld:pubmed
pubmed-article:21760968pubmed:authorpubmed-author:QipshidzeNati...lld:pubmed
pubmed-article:21760968pubmed:authorpubmed-author:AweOlubusayoOlld:pubmed
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pubmed-article:21760968pubmed:pagination97-106lld:pubmed
pubmed-article:21760968pubmed:year2011lld:pubmed
pubmed-article:21760968pubmed:articleTitleExercise mitigates homocysteine - ?2-adrenergic receptor interactions to ameliorate contractile dysfunction in diabetes.lld:pubmed
pubmed-article:21760968pubmed:publicationTypeJournal Articlelld:pubmed