Exercise mitigates homocysteine - β2-adrenergic receptor interactions to ameliorate contractile dysfunction in diabetes

Paras Kumar Mishra, Olubusayo Awe, Naira Metreveli, Natia Qipshidze, Irving G. Joshua, Suresh C. Tyagi

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

We tested the hypothesis that exercise ameliorates contractile dysfunction by interfering with homocysteine - β2-adrenergic receptor (AR) interactions, inducing β2-adrenergic response and Gs (stimulatory G adenylyl cyclase dependent protein kinase), and lowering homocysteine level in diabetes. The effect of homocysteine on β2-AR was determined by (a) scoring the β2-AR in the cardiomyocytes treated with high dose of homocysteine using flow cytometry, and (b) co-localizing homocysteine with Gs (an inducer of β2-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 β2-AR in diabetes was evaluated by co-immunoprecipitation in the four groups of db/db mice: (1) sedentary, (2) treated with salbutamol (a β2-AR agonist), (3) swimming exercise, and (4) swimming + salbutamol treatment. The effect of exercise on β2-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 β2-AR and inhibits Gs in diabetes. However, exercise mitigates the interactions of homocysteine with β2-AR and induces β2-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 β2-AR response in diabetes and effect of exercise on homocysteine - β2-AR interactions.

Original languageEnglish (US)
Pages (from-to)97-106
Number of pages10
JournalInternational Journal of Physiology, Pathophysiology and Pharmacology
Volume3
Issue number2
StatePublished - Jul 14 2011
Externally publishedYes

Fingerprint

Homocysteine
Adrenergic Receptors
Cardiac Myocytes
Albuterol
Calcium
Adrenergic Agonists
Immunoprecipitation
Adenylyl Cyclases
Confocal Microscopy
Adrenergic Agents
Protein Kinases
Echocardiography
Flow Cytometry
Proteins
Western Blotting
Polymerase Chain Reaction

Keywords

  • Cardiomyopathy
  • Echocardiogram
  • Gs
  • HL1
  • Heart failure
  • db/db

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Physiology
  • Physiology (medical)

Cite this

Exercise mitigates homocysteine - β2-adrenergic receptor interactions to ameliorate contractile dysfunction in diabetes. / Mishra, Paras Kumar; Awe, Olubusayo; Metreveli, Naira; Qipshidze, Natia; Joshua, Irving G.; Tyagi, Suresh C.

In: International Journal of Physiology, Pathophysiology and Pharmacology, Vol. 3, No. 2, 14.07.2011, p. 97-106.

Research output: Contribution to journalArticle

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