title: Myeloperoxidase-mediated oxidation targets serum apolipoprotein A-I in diabetic patients and represents a potential mechanism leading to impaired anti-apoptotic activity of high density lipoprotein.
abstract: BACKGROUND
  It is demonstrated that levels of protein-bound chlorotyrosine, nitrotyrosine and myeloperoxidase (MPO), a protein that catalyzes generation of chlorinating and nitrating oxidants, serve as independent predictors of cardiovascular disease.
  
  
  METHODS
  Immunoprecipitation and Western blot were used to analyze protein concentration, nitration and chlorination. LC-MS/MS was used to identify nitrated and chlorinated sites of Tyr from immunoprecipitated serum proteins.
  
  
  RESULTS
  Apolipoprotein A-I (apoA-I), the primary protein constituent of high density lipoprotein (HDL), was identified as a selective target for MPO-catalyzed nitration and chlorination in patients with type 2 diabetes. The serum proteins from diabetic subjects showed that the levels of apoA-I nitration and chlorination were clearly increased, whereas apoA-I concentration and cholesterol efflux activity were significantly decreased. MPO as a likely mechanism for oxidative modification of apoA-I in vivo was apparently facilitated by MPO binding to apoA-I. Subsequently, it was found that Tyr 192 was the major nitration and chlorination site in apoA-I from diabetic serum. Further studies in vitro revealed that besides the classic inhibition in cholesterol efflux activities, MPO-catalyzed oxidation could result in a loss of anti-apoptotic activity of lipoprotein.
  
  
  CONCLUSIONS
  ApoA-I undergoes MPO-mediated oxidation in serum from diabetic patients compared to non-diabetic subjects and MPO-catalyzed modification may impair the anti-apoptotic properties of HDL in vitro.
authors.affiliation: Key Laboratory of Functional Small Organic Molecule, Ministry of Education and College of Life Science, Jiangxi Normal University, 99 Ziyang Road, Nanchang, Jiangxi 330022, China. Electronic address: naihaolu@gmail.com.
authors.forename: Naihao
authors.initials: N
authors.lastname: Lu
authors.affiliation: Key Laboratory of Green Chemistry, Jiangxi Province and College of Chemistry and Chemical Engineering, Jiangxi Normal University, 99 Ziyang Road, Nanchang, Jiangxi, 330022, China.
authors.forename: Shiliang
authors.initials: S
authors.lastname: Xie
authors.affiliation: Key Laboratory of Green Chemistry, Jiangxi Province and College of Chemistry and Chemical Engineering, Jiangxi Normal University, 99 Ziyang Road, Nanchang, Jiangxi, 330022, China.
authors.forename: Jiayu
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Green Chemistry, Jiangxi Province and College of Chemistry and Chemical Engineering, Jiangxi Normal University, 99 Ziyang Road, Nanchang, Jiangxi, 330022, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Tian
authors.affiliation: Key Laboratory of Functional Small Organic Molecule, Ministry of Education and College of Life Science, Jiangxi Normal University, 99 Ziyang Road, Nanchang, Jiangxi 330022, China; Key Laboratory of Green Chemistry, Jiangxi Province and College of Chemistry and Chemical Engineering, Jiangxi Normal University, 99 Ziyang Road, Nanchang, Jiangxi, 330022, China. Electronic address: yiyuanpeng@yahoo.com.
authors.forename: Yi-Yuan
authors.initials: YY
authors.lastname: Peng
mesh_terms: D016632:Apolipoprotein A-I / Q000097:blood / Q000302:isolation & purification / Q000378:metabolism*; D017209:Apoptosis; D055162:Biocatalysis; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D008075:Lipoproteins, HDL / Q000097:blood / Q000302:isolation & purification / Q000378:metabolism*; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
chemical_list: C505693:APOA1 protein, human; D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; D009195:Peroxidase
keywords: Apolipoprotein A-I; Diabetes; Free radicals; MPO; Oxidative modification