title: Reactive carbonyl compounds (RCCs) cause aggregation and dysfunction of fibrinogen.
abstract: Fibrinogen is a key protein involved in coagulation and its deposition on blood vessel walls plays an important role in the pathology of atherosclerosis. Although the causes of fibrinogen (fibrin) deposition have been studied in depth, little is known about the relationship between fibrinogen deposition and reactive carbonyl compounds (RCCs), compounds which are produced and released into the blood and react with plasma protein especially under conditions of oxidative stress and inflammation. Here, we investigated the effect of glycolaldehyde on the activity and deposition of fibrinogen compared with the common RCCs acrolein, methylglyoxal, glyoxal and malondialdehyde. At the same concentration (1 mmol/L), glycolaldehyde and acrolein had a stronger suppressive effect on fibrinogen activation than the other three RCCs. Fibrinogen aggregated when it was respectively incubated with glycolaldehyde and the other RCCs, as demonstrated by SDS-PAGE, electron microscopy and intrinsic fluorescence intensity measurements. Staining with Congo Red showed that glycolaldehyde- and acrolein-fibrinogen distinctly formed amyloid-like aggregations. Furthermore, the five RCCs, particularly glycolaldehyde and acrolein, delayed human plasma coagulation. Only glycolaldehyde showed a markedly suppressive effect on fibrinogenesis, none did the other four RCCs when their physiological blood concentrations were employyed, respectively. Taken together, it is glycolaldehyde that suppresses fibrinogenesis and induces protein aggregation most effectively, suggesting a putative pathological process for fibrinogen (fibrin) deposition in the blood.
authors: State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors: Ya-Jie
authors: YJ
authors: Xu
authors: Min
authors: M
authors: Qiang
authors: Jin-Ling
authors: JL
authors: Zhang
authors: Ying
authors: Y
authors: Liu
authors: Rong-Qiao
authors: RQ
authors: He
mesh_terms: D000079:Acetaldehyde / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry; D000171:Acrolein / Q000097:blood / Q000737:chemistry; D001777:Blood Coagulation; D003224:Congo Red; D004591:Electrophoresis, Polyacrylamide Gel; D005340:Fibrinogen / Q000737:chemistry* / Q000378:metabolism; D006037:Glyoxal / Q000097:blood / Q000737:chemistry; D006801:Humans; D008315:Malondialdehyde / Q000737:chemistry; D058105:Polymerization; D050050:Protein Carbonylation; D011765:Pyruvaldehyde / Q000097:blood / Q000737:chemistry; D012996:Solutions; D013050:Spectrometry, Fluorescence; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013917:Thrombin / Q000737:chemistry
chemical_list: D012996:Solutions; D003224:Congo Red; D008315:Malondialdehyde; D006037:Glyoxal; D011765:Pyruvaldehyde; D000171:Acrolein; D005340:Fibrinogen; D013917:Thrombin; D000079:Acetaldehyde; C010972:glycolaldehyde