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Related Experiment Video

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Isolation, Culture and Transduction of Adult Mouse Cardiomyocytes
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Cardiomyocyte Ogt is essential for postnatal viability.

Lewis J Watson1, Bethany W Long, Angelica M DeMartino

  • 1Department of Physiology and Biophysics, University of Louisville, Louisville, Kentucky; and.

American Journal of Physiology. Heart and Circulatory Physiology
|November 5, 2013
PubMed
Summary

Cardiomyocyte O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase (Ogt) is crucial for heart maturation. Loss of Ogt in adult cardiomyocytes leads to progressive heart failure, highlighting its essential role in maintaining cardiac function.

Keywords:
O-linked-β-N-acetylglucosamine transferasecardiac functionhypertrophymetabolismremodelinguridine diphospho-N-acetylglucosamine:polypeptide β-N-acetylglucosaminyltransferase

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Area of Science:

  • Cardiovascular Biology
  • Molecular Cardiology
  • Developmental Biology

Background:

  • O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase (Ogt) is vital for embryonic development.
  • Acute increases in O-GlcNAcylation show cardioprotective effects.
  • The role of Ogt in cardiac function and maturation is largely unknown due to lethality of global knockouts.

Purpose of the Study:

  • To investigate the role of cardiomyocyte Ogt in cardiac maturation and function.
  • To characterize the effects of constitutive and inducible cardiomyocyte-specific Ogt deletion on heart development and physiology.

Main Methods:

  • Generation and characterization of constitutive cardiomyocyte-specific Ogt knockout (c-cmOGT KO) mice.
  • Assessment of cardiac morphology, function, fibrosis, apoptosis, and hypertrophy in KO mice.
  • Analysis of gene expression, mitochondrial respiration, and endoplasmic reticulum stress markers.
  • Utilizing inducible deletion models to study long-term Ogt loss in adult cardiomyocytes.

Main Results:

  • Constitutive c-cmOGT KO mice exhibited reduced survival, smaller size, dilated hearts, and signs of heart failure.
  • KO hearts showed increased fibrosis, apoptosis, hypertrophy, and elevated glycolytic gene expression.
  • Evidence of endoplasmic reticulum stress was observed, with increased GRP78 and PDI expression.
  • Inducible deletion resulted in progressive cardiomyopathy over time, confirming Ogt's necessity in adult hearts.

Conclusions:

  • Cardiomyocyte Ogt is essential for proper mammalian heart maturation.
  • Loss of Ogt in adult cardiomyocytes leads to progressive ventricular dysfunction and cardiomyopathy.
  • Targeting Ogt may offer therapeutic potential for heart failure, but its role in mature cardiac function needs further elucidation.