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A distinctive histidine residue is essential for in vivo glycation-inactivation of human CD59 transgenically expressed in mice erythrocytes: Implications for human diabetes complications
- Source :
- American Journal of Hematology. 92:1198-1203
- Publication Year :
- 2017
- Publisher :
- Wiley, 2017.
-
Abstract
- Clinical and experimental evidences support a link between the complement system and the pathogenesis of diabetes complications. CD59, an extracellular cell membrane-anchored protein, inhibits formation of the membrane attack complex (MAC), the main effector of complement-mediated tissue damage. This complement regulatory activity of human CD59 (hCD59) is inhibited by hyperglycemia-induced ɛ-amino glycation of Lys41 . Biochemical and structural analyses of glycated proteins with known three-dimensional structure revealed that glycation of ɛ-amino lysyl residues occurs predominantly at "glycation motives" that include lysyl/lysyl pairs or proximity of a histidyl residue, in which the imidazolyl moiety is ≈ 5A from the ɛ-amino group. hCD59 contains a distinctive Lys41 /His44 putative glycation motif within its active site. In a model of transgenic diabetic mice expressing in erythrocytes either the wild type or a H44Q mutant form of hCD59, we demonstrate in vivo that the His44 is required for Lys41 glycation and consequent functional inactivation of hCD59, as evidenced using a mouse erythrocytes hemolytic assay. Since (1) the His44 residue is not present in CD59 from other animal species and (2) humans are particularly prone to develop complications of diabetes, our results indicate that the Lys41 /His44 glycation motif in human CD59 may confer humans a higher risk of developing vascular disease in response to hyperglycemia.
- Subjects :
- Blood Glucose
0301 basic medicine
Erythrocytes
Glycosylation
Lysine
CD59 Antigens
Mice, Transgenic
CD59
Biology
Hemolysis
Article
Diabetes Mellitus, Experimental
Diabetes Complications
Mice
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Glycation
Animals
Humans
Histidine
Effector
Erythrocyte Membrane
Wild type
Hematology
Complement system
030104 developmental biology
Gene Expression Regulation
chemistry
Biochemistry
030220 oncology & carcinogenesis
Mutation
Complement membrane attack complex
Subjects
Details
- ISSN :
- 03618609
- Volume :
- 92
- Database :
- OpenAIRE
- Journal :
- American Journal of Hematology
- Accession number :
- edsair.doi.dedup.....1a42764d587f2afc26e7b1e34e439b2f