Role of O-GlcNAc glycosylation in diabetic cataract

Abstract

AIM:To analyze the expression changes of O-linked N-acetylglucosamine(O-GlcNAc)glycoprotein in the lens capsule of age-related cataract and diabetic cataract and investigate the role of O-GlcNAc glycoprotein in diabetic cataract.METHODS: The lens capsules of 54 patients(56 eyes)with diabetic cataract and 115 patients(120 eyes )with age-related cataract were studied. Immunoblotting was used to detect the expression level of O-GlcNAc protein in the lens capsules of age-related and diabetic cataracts, and mass spectrometry was used to identify the O-GlcNAc glycoproteins in lens capsules.RESULTS: Immunoblotting results showed that the expression level of O-GlcNAc protein in the lens capsule of diabetic cataracts was significantly higher than in the age-related cataracts(P<0.01). With the level of glycosylated hemoglobin increasing, the expression level of O-GlcNAc protein also increased(P<0.01). Totally 5 O-GlcNAc proteins with up-regulated expression(FABP5, KRT16, PGK1, CTSD and S100A7), and 18 O-GlcNAc proteins with down-regulated expression(CRYβB1, etc.)were identified in the lens capsule of patients with diabetic cataract by mass spectrometry. Three new O-GlcNAc glycosylation sites were identified in this study. They were O-GlcNAcylation at T1730 position and S1738 position of PTPRQ and O-GlcNAcylation at T61 position of ATP5MC2.CONCLUSION:O-GlcNAc glycosylation may be involved in the formation and development of diabetic cataract. The differential O-GlcNAc glycoprotein identified by mass spectrometry provided the data for further study about pathogenesis of diabetic cataract.

Keywords

• o-linked n-acetylglucosamine(o-glcnac)glycosylation
• diabetic cataract
• age-related cataract
• lens capsule
• mass spectrometry