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Int J Physiol Pathophysiol Pharmacol 2011;3(2):97-106.
Original Article
Exercise mitigates the homocysteine - beta2-adrenergic receptor interactions to
ameliorate contractile dysfunction in diabetes
Paras Kumar Mishra, Olubusayo Awe, Naira Metreveli, Natia Quipshidze, Irving G. Joshua, Suresh C. Tyagi
Department of Physiology & Biophysics, School of Medicine, University of Louisville, Louisville, Kentucky 40202, USA
Received April 22, 2011; accepted April, 2011; Epub April, 2011; Published June 15, 2011
Abstract: We tested the hypothesis that exercise ameliorates contractile dysfunction by interfering with the homocysteine – beta2-
adrenergic receptor (AR) interactions, inducing beta2-adrenergic response and Gs (stimulatory G adenylyl cyclase dependent protein
kinase), and lowering homocysteine level in diabetes. The effect of homocysteine on beta2-AR was determined by (a) scoring the
beta2-AR in the cardiomyocytes treated with high dose of homocysteine using flow cytometry, and (b) co-localizing homocysteine and
Gs (an inducer of beta2-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 beta2-AR in diabetes was evaluated by co-
immunoprecipitation in the four groups of db/db mice: (1) sedentary (DB), (2) treated with salbutamol (DBS), (3) swimming exercise
(DBE), and (4) swimming + salbutamol treatment. The effect of exercise on beta2-AR was determined by RT-PCR and Western blotting
while cardiac dysfunction was assessed by echocardiography, and contractility and calcium handling of cardiomyocytes from the above
four groups. The results revealed that elevated level of homocysteine decreases the number of beta2-AR and inhibits Gs in diabetes.
However, exercise mitigates the interactions of homocysteine with beta2-AR and induces beta2-AR. Exercise also ameliorates cardiac
dysfunction by enhancing the calcium handling of cardiomyocytes. To our knowledge, this is the first report showing mechanism of
homocysteine mediated attenuation of beta2-AR response in diabetes and effect of exercise on homocysteine - beta2-AR interactions.
(IJPPP1104002).
Key words: Cardiomyopathy, heart failure, echocardiogram, Gs, HL1, db/db
Full Text PDF
Address all correspondence to:
Paras Kumar Mishra, PhD
Department of Physiology & Biophysics
University of Louisville School of Medicine
500 South Preston Street, HSC-A, Room-1216,
Louisville, KY 40202, USA
Tel: 502-852-3627
Fax: 502-852-6239
E-mail: pkmish01@louisville.edu
Original Article
Exercise mitigates the homocysteine - beta2-adrenergic receptor interactions to
ameliorate contractile dysfunction in diabetes
Paras Kumar Mishra, Olubusayo Awe, Naira Metreveli, Natia Quipshidze, Irving G. Joshua, Suresh C. Tyagi
Department of Physiology & Biophysics, School of Medicine, University of Louisville, Louisville, Kentucky 40202, USA
Received April 22, 2011; accepted April, 2011; Epub April, 2011; Published June 15, 2011
Abstract: We tested the hypothesis that exercise ameliorates contractile dysfunction by interfering with the homocysteine – beta2-
adrenergic receptor (AR) interactions, inducing beta2-adrenergic response and Gs (stimulatory G adenylyl cyclase dependent protein
kinase), and lowering homocysteine level in diabetes. The effect of homocysteine on beta2-AR was determined by (a) scoring the
beta2-AR in the cardiomyocytes treated with high dose of homocysteine using flow cytometry, and (b) co-localizing homocysteine and
Gs (an inducer of beta2-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 beta2-AR in diabetes was evaluated by co-
immunoprecipitation in the four groups of db/db mice: (1) sedentary (DB), (2) treated with salbutamol (DBS), (3) swimming exercise
(DBE), and (4) swimming + salbutamol treatment. The effect of exercise on beta2-AR was determined by RT-PCR and Western blotting
while cardiac dysfunction was assessed by echocardiography, and contractility and calcium handling of cardiomyocytes from the above
four groups. The results revealed that elevated level of homocysteine decreases the number of beta2-AR and inhibits Gs in diabetes.
However, exercise mitigates the interactions of homocysteine with beta2-AR and induces beta2-AR. Exercise also ameliorates cardiac
dysfunction by enhancing the calcium handling of cardiomyocytes. To our knowledge, this is the first report showing mechanism of
homocysteine mediated attenuation of beta2-AR response in diabetes and effect of exercise on homocysteine - beta2-AR interactions.
(IJPPP1104002).
Key words: Cardiomyopathy, heart failure, echocardiogram, Gs, HL1, db/db
Full Text PDF
Address all correspondence to:
Paras Kumar Mishra, PhD
Department of Physiology & Biophysics
University of Louisville School of Medicine
500 South Preston Street, HSC-A, Room-1216,
Louisville, KY 40202, USA
Tel: 502-852-3627
Fax: 502-852-6239
E-mail: pkmish01@louisville.edu
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