Under normal conditions, the ubiquitously expressed αB-crystallin functions as a chaperone. αB-crystallin has been implicated in a variety of pathologies, consistent with a build-up of protein aggregates, such as neuromuscular disorders, myofibrillar myopathies, and cardiomyopathies. αB-crystallins' cardioprotection is partially attributed to its translocation and binding to cytoskeletal elements in response to stress. The triggers for this translocation are not clearly understood. In the heart, αB-crystallin undergoes at least three significant post-translational modifications: phosphorylation at ser-45 and 59 and O-GlcNAcylation (O-linked attachment of the monosaccharide β-N-acetyl-glucosamine) at thr-170. Whether phosphorylation status drives translocation remains controversial. Therefore, we evaluated the role of αB-crystallins' O-GlcNAcylation in its stress-induced translocation and cytoprotection in cardiomyocytes under stress. Immunoblotting and precipitation experiments with anti-O-GlcNAc antibody (CTD110.6) and glycoprotein staining (Pro-Q Emerald) both demonstrate robust stress-induced O-GlcNAcylation of αB-crystallin. A non-O-GlcNAcylatable αB-crystallin mutant (αB-T170A) showed diminished translocation in response to heat shock and robust phosphorylation at both ser-45 and ser-59. Cell survival assays show a loss of overexpression-associated cytoprotection with the non-glycosylatable mutant to multiple stresses. While ectopic expression of wild-type αB-crystallin strongly stabilized ZsProSensor, a fusion protein rapidly degraded by the proteasome, the non-O-GlcNAcylatable version did not. Therefore, we believe the O-GlcNAcylation of αB-crystallin is a dynamic and important regulator of both its localization and function.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1007/s11010-013-1627-5 | DOI Listing |
Prev Nutr Food Sci
December 2024
Aging and Metabolism Research Group, Food Functionality Research, Korea Food Research Institute, Wanju 55365, Korea.
Vascular smooth muscle cells (VSMCs) undergo metabolic pathway transitions, including aerobic glycolysis, fatty acid oxidation, and amino acid metabolism, which are important for their function. Metabolic dysfunction in VSMCs can lead to age-related vascular diseases. -GlcNAcylation, a nutrient-dependent posttranslational modification linked specifically to glucose metabolism, plays an important role in this context.
View Article and Find Full Text PDFCell Biochem Biophys
January 2025
Department of Obstetrics, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, 361003, China.
O-linked N-acetylglucosamine transferase (OGT)-catalyzed O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation) is closely associated with diabetes progression. This study aims to investigate the mechanism of OGT in regulating endothelial dysfunction in gestational diabetes mellitus (GDM). Expressions of OGT, O-linked N-acetylglucosamine (O-GlcNAc), enhancer of zeste homolog 2 (EZH2), and HEK27me3 in human umbilical vein endothelial cells (HUVECs) and GDM-derived HUVECs (GDM-HUVECs) were assessed by western blot.
View Article and Find Full Text PDFAlzheimers Dement (N Y)
December 2024
Eli Lilly and Company Indianapolis Indiana USA.
Introduction: The aggregation and spread of hyperphosphorylated, pathological tau in the human brain is hypothesized to play a key role in Alzheimer's disease (AD) as well as other neurogenerative tauopathies. O-GlcNAcylation, an important post-translational modification of tau and many other proteins, is significantly decreased in brain tissue of AD patients relative to healthy controls. Increased tau O-GlcNAcylation has been shown to reduce tau pathology in mouse in vivo tauopathy models.
View Article and Find Full Text PDFFront Immunol
January 2025
Department of Clinical Laboratory Medicine, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, China.
PLoS One
December 2024
Department of Gastroenterology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Ulcerative colitis (UC) is an immune-related inflammatory bowel disease, with its underlying mechanisms being a central area of clinical research. O-GlcNAcylation plays a critical role in regulating immunity progression and the occurrence of inflammatory diseases and tumors. Yet, the mechanism of O-GlcNAc-associated colitis remains to be elucidated.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!