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(Circulation Research. 2005;96:925.)
© 2005 American Heart Association, Inc.

Editorials

A Bittersweet Modification

O-GlcNAc and Cardiac Dysfunction

Steven P. Jones

From the Institute of Molecular Cardiology, University of Louisville, Louisville, Ky.

Correspondence to: Steven P. Jones, PhD, Institute of Molecular Cardiology, Department of Medicine, University of Louisville, 570 S. Preston St, Baxter I-119, Louisville, KY 40202. E-mail Steven.P.Jones@Louisville.edu

See related article, pages 1006–1013

Key Words: glycosylation • post-translational modification • glucose

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Data from the Framingham Study indicate that cardiac dysfunction in diabetic patients may occur without documented cardiovascular disease.¹ Given the profound metabolic disturbance underlying diabetes, such dysfunction may not be surprising. Although it would be tempting to ascribe such dysfunction to simple energetic disturbances, a study in the current issue of Circulation Research² suggests a specific and rather unusual suspect in cardiac biology.

The inability to handle glucose properly is a hallmark of diabetes. Of course, during any dialogue of glucose handling, discussants often focus on glycolysis or glycogen storage. Although up to 99% of intracellular glucose is destined for such fates, a small fraction (1% to 5%) of intracellular glucose is diverted to the hexosamine biosynthetic pathway which culminates in the formation of low millimolar levels of cytoplasmic uridine diphospho-N-acetylglucosamine (UDP-GlcNAc). Cells use cytoplasmic stores of UDP-GlcNAc for a variety of cell processes, but the present discussion focuses on one particular function: beta O-linkage of GlcNAc (O-GlcNAc) to intracellular proteins.

Unlike Golgi-mediated cotranslational modifications associated with the serial N-linkage of sugars, the O-linkage of GlcNAc occurs posttranslationally and is highly dynamic.³ There are 2 known enzymes regulating the presence of O-GlcNAc on proteins. Using UDP-GlcNAc as the monosaccharide donor, O-GlcNAc transferase (OGT) adds GlcNAc to proteins at serine or threonine residues whereas O-GlcNAcase removes the sugar moiety. Alterations in intracellular glucose flux can directionally change levels of the O-GlcNAc modification. Thus, a modified monosaccharide originating from glucose can . . . [Full Text of this Article]

Related Article:

Adenovirus-Mediated Overexpression of O-GlcNAcase Improves Contractile Function in the Diabetic Heart

Ying Hu, Darrell Belke, Jorge Suarez, Eric Swanson, Raymond Clark, Masahiko Hoshijima, and Wolfgang H. Dillmann
Circ. Res. 2005 96: 1006-1013. [Abstract] [Full Text] [PDF]

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