Glycobiology Advance Access published online on April 15, 2005
Glycobiology, doi:10.1093/glycob/cwi061
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1 Department of Biochemistry and Molecular Biology; The Oklahoma Center for Medical Glycobiology; College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104; College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190
* To whom correspondence should be addressed. Cystic Fibrosis (CF) is the most lethal genetic disorder in Caucasians and is characterized by production of excessive amounts of viscous mucus secretions in the airways of patients, leading to airway obstruction, chronic bacterial infections, and respiratory failure. Previous studies indicate that CF-derived airway mucins are glycosylated and sulfated differently compared to mucins from non-diseased (ND) individuals. To address unresolved questions about mucin glycosylation and sulfation we examined O-glycan structures in mucins purified from mucus secretions of two CF donors versus two non-diseased ND donors. All mucins contained galactose (Gal), N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc), fucose (Fuc), and sialic acid (Neu5Ac). However, CF mucins had higher sugar content and more O-glycans compared to ND mucins. Both ND and CF mucins contained GlcNAc-6-Sulfate, Gal-6-Sulfate, and Gal-3-Sulfate, but CF mucins had higher amounts of the 6-sulfated species. O-glycans were released from CF- and ND-mucins and derivatized with 2-aminobenzamide, separated by ion exchange chromatography, and quantified by fluorescence. There was nearly a two-fold increase in sulfation and sialylation in CF- compared to ND-mucin. HPLC profiles of glycans showed differences between the two CF samples compared to the two ND samples. Glycan compositions were defined by MALDI-TOF mass spectrometry. Unexpectedly, 260 compositional types of O-glycans were identified, and CF mucins contained a higher proportion of sialylated and sulfated O-glycans compared to ND mucins. These profound structural differences in mucin glycosylation in CF patients may contribute to inflammatory responses and increased pathogenesis by Pseudomonas aeruginosa.
Received October 13, 2004
Revised March 31, 2005
Accepted April 1, 2005
Article
Altered O-Glycosylation and Sulfation of Airway Mucins Associated with Cystic Fibrosis
2 Pediatric Pulmonary and Cystic Fibrosis Center; Department of Pediatrics; College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104
3 College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190
4 The Oklahoma Center for Medical Glycobiology; College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190
5 Department of Biochemistry and Molecular Biology; The Oklahoma Center for Medical Glycobiology; College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104
Richard D. Cummings, E-mail: richard-cummings{at}ouhsc.edu
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