Excessive O-GlcNAcylation of proteins suppresses spontaneous cardiogenesis in ES cells

Hoe-Suk Kim1, Sang Yoon Park, Yu Rim Choi

  • 1Medical Research Center, Seoul National University, Seoul, Republic of Korea. hoeskim@hotmail.com

FEBS Letters
|July 14, 2009
PubMed

Insights

Excessive O-linked N-acetylglucosamine (O-GlcNAc) modification impairs cardiac cell differentiation. This study shows that altering O-GlcNAcylation levels in embryonic stem cells affects cardiomyocyte development.

Area of Science:

  • Biochemistry
  • Developmental Biology
  • Cardiovascular Research

Background:

  • Aberrant protein O-linked N-acetylglucosamine (O-GlcNAc) modification is linked to diabetic cardiomyopathy.
  • Embryonic stem (ES) cells offer a model to study early developmental processes, including cardiac differentiation.

Purpose of the Study:

  • To investigate the role of O-GlcNAcylation in cardiomyocyte development using Nkx2.5GFP knock-in ES cells.
  • To determine how modulating O-GlcNAcylation impacts cardiac differentiation and gene expression.

Main Methods:

  • Utilized Nkx2.5GFP knock-in ES cells to track cardiomyocyte differentiation.
  • Manipulated O-GlcNAcylation levels using glucosamine, streptozotocin, PUGNAc, and 6-diazo-5-oxo-norleucine.
  • Assessed cardiomyocyte precursor numbers and cardiac-specific gene expression.

Main Results:

  • O-GlcNAcylation and O-GlcNAc transferase expression decreased during ES cell differentiation.
  • Increased O-GlcNAcylation reduced cardiomyocyte precursor numbers and cardiac gene expression.
  • Decreased O-GlcNAcylation enhanced cardiomyocyte precursor formation.

Conclusions:

  • Excessive O-GlcNAcylation negatively impacts cardiac cell differentiation in ES cells.
  • O-GlcNAcylation is a critical regulator of early cardiac development.
  • Findings suggest a potential therapeutic target for conditions involving impaired cardiac development.

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