Associations of dicarbonyl stress with complement activation: the CODAM study
Ying Xin1,2,3, Elisabeth Hertle1,2, Carla J H van der Kallen1,2
1Department of Internal Medicine, Maastricht University Medical Centre, Universiteitssingel 50, PO Box 616, 6200 MD, Maastricht, the Netherlands.
Diabetologia
|January 30, 2020
Summary
Dicarbonyl stress, linked to AGEs, impacts complement regulators. Some dicarbonyl markers inversely correlated with complement activation, while pentosidine positively associated with sC5b-9, indicating varied biological roles.
Area of Science:
- Biochemistry and Molecular Biology
- Immunology
- Metabolic Disease Research
Background:
- Reactive α-dicarbonyl compounds are key precursors to advanced glycation end products (AGEs).
- Glycation of complement regulatory proteins can alter their ability to inhibit complement activation.
- The relationship between dicarbonyl stress and complement activation in humans requires further investigation.
Purpose of the Study:
- To investigate the association between dicarbonyl stress and complement activation in a human cohort.
- To explore the impact of specific dicarbonyl stress markers and AGEs on complement activation products C3a and sC5b-9.
- To evaluate the role of glyoxalase 1 (GLO1) gene polymorphisms in modulating complement activation.
Main Methods:
- Measured circulating concentrations of α-dicarbonyls (MGO, GO, 3-DG), free and protein-bound AGEs (CML, CEL, pentosidine, MG-H1), and complement activation products (C3a, sC5b-9) in 530 participants.
- Employed multiple linear regression analyses to assess associations between standardized dicarbonyl stress and complement activation, adjusting for confounders.
- Examined associations of GLO1 polymorphisms (rs1049346, rs2736654) with C3a and sC5b-9 levels.
Main Results:
- Plasma glyoxal (GO) was inversely associated with sC5b-9, and protein-bound Nε-(carboxyethyl)lysine (CEL) inversely associated with C3a.
- Protein-bound pentosidine showed a positive association with sC5b-9.
- GLO1 rs1049346 polymorphism was associated with lower sC5b-9 concentrations, but rs2736654 showed no significant association with complement products.
Conclusions:
- Dicarbonyl stress markers exhibit distinct associations with complement activation products.
- The positive association of pentosidine with sC5b-9 suggests a specific role in complement activation.
- These findings highlight the complex biological relationships between individual dicarbonyl stress markers and complement system activity.
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