title: Increased O-GlcNAcylation of NF-κB Enhances Retinal Ganglion Cell Death in Streptozotocin-induced Diabetic Retinopathy.
abstract: OBJECTIVE
  Hyperglycemia results in increased flux through the hexoxamine biosynthetic pathway. We examined whether hyperglycemia increases O-GlcNAcylation in the diabetic retina and whether elevated O-GlcNAcylation of nuclear factor (NF)-κB increases apoptosis of retinal ganglion cells (RGCs) in diabetic retinopathy (DR).
  
  
  METHODS
  Diabetes was induced in C57BL/6 mice by five consecutive intraperitoneal injections of 55 mg/kg streptozotocin. All mice were killed 2 months after injections and expression levels of O-GlcNAcylated proteins, O-linked N-acetylglucosamine transferase (OGT), β-d-N-acetylglucosaminidase and NF-κB, and the extent of RGC death were examined. Immunoprecipitations were performed to investigate whether O-GlcNAcylation of NF-κB led to its activation and RGC death in DR.
  
  
  RESULTS
  The expression levels of O-GlcNAcylated proteins and OGT were markedly higher in diabetic retinas than in control retinas. OGT colocalized with NeuN, a RGC-specific marker, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells in the ganglion cell layer of diabetic retinas. The p65 subunit of NF-κB was O-GlcNAcylated and the level of O-GlcNAcylated p65 was higher in diabetic retinas than in control retinas.
  
  
  CONCLUSIONS
  The present data suggest that hyperglycemia increases O-GlcNAcylation in DR and that O-GlcNAcylation of the p65 subunit of NF-κB is involved in hyperglycemia-induced NF-κB activation and RGC death in DR.
authors.affiliation: a Department of Ophthalmology , School of Medicine, Gyeongsang National University , Jinju , Korea .|b Institute of Health Science, Gyeongsang National University , Jinju , South Korea and.
authors.forename: Seong-Jae
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: a Department of Ophthalmology , School of Medicine, Gyeongsang National University , Jinju , Korea .
authors.forename: Woong-Sun
authors.initials: WS
authors.lastname: Yoo
authors.affiliation: b Institute of Health Science, Gyeongsang National University , Jinju , South Korea and.|c Department of Anatomy and Neurobiology , School of Medicine, Gyeongsang National University , Jinju , Korea.
authors.forename: Meeyoung
authors.initials: M
authors.lastname: Choi
authors.affiliation: a Department of Ophthalmology , School of Medicine, Gyeongsang National University , Jinju , Korea .|b Institute of Health Science, Gyeongsang National University , Jinju , South Korea and.
authors.forename: Inyoung
authors.initials: I
authors.lastname: Chung
authors.affiliation: a Department of Ophthalmology , School of Medicine, Gyeongsang National University , Jinju , Korea .|b Institute of Health Science, Gyeongsang National University , Jinju , South Korea and.
authors.forename: Ji-Myong
authors.initials: JM
authors.lastname: Yoo
authors.affiliation: b Institute of Health Science, Gyeongsang National University , Jinju , South Korea and.|c Department of Anatomy and Neurobiology , School of Medicine, Gyeongsang National University , Jinju , Korea.
authors.forename: Wan-Sung
authors.initials: WS
authors.lastname: Choi
mesh_terms: D000118:Acetylglucosaminidase / Q000378:metabolism*; D000215:Acylation; D000818:Animals; D017209:Apoptosis; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D003930:Diabetic Retinopathy / Q000378:metabolism* / Q000473:pathology; D006943:Hyperglycemia / Q000378:metabolism; D047468:Immunoprecipitation; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000473:pathology*; D051996:Transcription Factor RelA / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D017351:N-Acetylglucosaminyltransferases; C063057:UDP-N-acetylglucosamine-peptide beta-N-acetylglucosaminyltransferase; D000118:Acetylglucosaminidase
keywords: Diabetes; NF-κB; O-GlcNAcylation; ganglion cell death; retinopathy