New Insights into Metabolic Signaling and Cell Survival: The Role of β-O-Linkage ofN-Acetylglucosamine
- 3 September 2008
- journal article
- review article
- Published by American Society for Pharmacology & Experimental Therapeutics (ASPET) in Journal of Pharmacology and Experimental Therapeutics
- Vol. 327 (3), 602-609
- https://doi.org/10.1124/jpet.108.143263
Abstract
The involvement of glucose in fundamental metabolic pathways represents a core element of biology. Late in the 20th century, a unique glucose-derived signal was discovered, which appeared to be involved in a variety of cellular processes, including mitosis, transcription, insulin signaling, stress responses, and potentially, Alzheimer's disease, and diabetes. By definition, this glucose-fed signaling system was a post-translational modification to proteins. However, unlike classical cotranslational N-glycosylation occurring in the endoplasmic reticulum and Golgi apparatus, this process occurs elsewhere throughout the cell in a highly dynamic fashion, similar to the quintessential post-translational modification, phosphorylation. This more recently described post-translational modification, the β-O-linkage of N-acetylglucosamine (i.e., O-GlcNAc) to nucleocytoplasmic proteins, represents an under-investigated area of biology. This signaling system operates in all of the tissues examined and seems to have persisted throughout all multicellular eukaryotes. Thus, it comes with little surprise that O-GlcNAc signaling is an integral system and viable target for biomedical investigation. This system may be a boundless source for insight into a variety of diseases and yield numerous opportunities for drug design. This Perspective will address recent insights into O-GlcNAc signaling in the cardiovascular system as a paradigm for its involvement in other biological systems.Keywords
This publication has 78 references indexed in Scilit:
- Non-canonical glycosyltransferase modulates post-hypoxic cardiac myocyte death and mitochondrial permeability transitionJournal of Molecular and Cellular Cardiology, 2008
- Increased proteinO-GlcNAc modification inhibits inflammatory and neointimal responses to acute endoluminal arterial injuryAmerican Journal of Physiology-Heart and Circulatory Physiology, 2008
- Glucosamine protects neonatal cardiomyocytes from ischemia-reperfusion injury via increased protein O-GlcNAc and increased mitochondrial Bcl-2American Journal of Physiology-Cell Physiology, 2008
- AMP-activated Protein Kinase and p38 MAPK Activate O-GlcNAcylation of Neuronal Proteins during Glucose DeprivationJournal of Biological Chemistry, 2008
- IncreasedO-GlcNAc levels during reperfusion lead to improved functional recovery and reduced calpain proteolysisAmerican Journal of Physiology-Heart and Circulatory Physiology, 2007
- Glucosamine cardioprotection in perfused rat hearts associated with increasedO-linkedN-acetylglucosamine protein modification and altered p38 activationAmerican Journal of Physiology-Heart and Circulatory Physiology, 2007
- Reduction ofO-GlcNAc protein modification does not prevent insulin resistance in 3T3-L1 adipocytesAmerican Journal of Physiology-Endocrinology and Metabolism, 2007
- Role of protein O-linked N-acetyl-glucosamine in mediating cell function and survival in the cardiovascular systemCardiovascular Research, 2007
- Glutamine-induced protection of isolated rat heart from ischemia/reperfusion injury is mediated via the hexosamine biosynthesis pathway and increased protein O-GlcNAc levelsJournal of Molecular and Cellular Cardiology, 2007
- Caenorhabditis elegans ortholog of a diabetes susceptibility locus: oga-1 ( O -GlcNAcase) knockout impacts O -GlcNAc cycling, metabolism, and dauerProceedings of the National Academy of Sciences of the United States of America, 2006