PMID- 14669859
OWN - NLM
STAT- MEDLINE
DCOM- 20040406
LR  - 20190516
IS  - 0886-022X (Print)
IS  - 0886-022X (Linking)
VI  - 25
IP  - 6
DP  - 2003 Nov
TI  - Serum protein-bound 3,4-dihydroxyphenylalanine and related products of protein 
      oxidation and chronic hemodialysis.
PG  - 997-1009
AB  - INTRODUCTION: Protein-bound dihydroxyphenylalanine (PB-DOPA) and its oxidation 
      products are formed by free radical and oxidative attack on proteins. 
      Hemodialysis and uremic toxins can activate leukocytes leading to overproduction 
      of reactive oxygen species such as hydrogen peroxide and hypochlorous acid (HOCl) 
      that increases protein oxidation. METHODS: We have used a sensitive fluorometric 
      method to measure PB-DOPA and its oxidation products in proteins after 
      gamma-irradiation and incubation with HOCl and in serum from hemodialysis 
      patients and healthy controls. These PB-DOPA concentrations were compared with 
      those measured by HPLC (PB-DOPAHPLC). RESULTS: Fluorescent PB-DOPA increased 
      linearly with increasing amounts of human serum and with increasing amounts of 
      gamma-irradiated bovine serum albumin. Concentrations of fluorescent PB-DOPA 
      paralleled PB-DOPAHPLC levels but were approximately 60-70 times higher. 
      Incubation of BSA and human serum albumin (HSA) with HOCl (39.4 mM) significantly 
      (P < 0.0001) increased fluorescent PB-DOPA by 5 fold and 10 fold respectively and 
      PB-DOPAHPLC by 6-fold for both proteins Fluorescent PB-DOPA concentration 
      increased significantly (P < 0.0001) by 16-fold in human serum incubated with 
      HOCl (39.4 mM). Mean serum fluorescent PB-DOPA was significantly (P < 0.0001) 
      higher in 19 hemodialysis patients (57.7 +/- 16.1 microM) compared with 21 
      healthy controls (33.5 +/- 3.7 microM). Mean PB-DOPAHPLC was 4.45 +/- 1.63 microM 
      in the healthy controls and 12 hemodialysis patients had values within the range 
      of values in these controls while five patients had values that were outside 
      eight SDs of the mean for healthy subjects. Serum fluorescent PB-DOPA was not 
      correlated significantly with PB-DOPAHPLC in these subjects. CONCLUSIONS: The 
      results of this study suggest that fluorophores of the type, which are derived 
      from DOPA can be reproducibly measured in delipidated serum protein and that HOCl 
      can increase levels of these fluorophores-generating proteins and may potentially 
      contribute to the high levels in serum from hemodialysis patients. This high 
      level of fluorescent PB-DOPA compounds is only partially due to authentic PB-DOPA 
      and might also be derived from other related protein oxidation products including 
      those from DOPA oxidation.
FAU - Sutherland, Wayne H F
AU  - Sutherland WH
AD  - Department of Medical and Surgical Sciences, University of Otago, Dunedin, New 
      Zealand. wayne.Sutherland@stonebow.otago.ac.nz
FAU - Gieseg, Steven P
AU  - Gieseg SP
FAU - Walker, Robert J
AU  - Walker RJ
FAU - de Jong, Sylvia A
AU  - de Jong SA
FAU - Firth, Carole A
AU  - Firth CA
FAU - Scott, Nicola
AU  - Scott N
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - England
TA  - Ren Fail
JT  - Renal failure
JID - 8701128
RN  - 0 (Biomarkers)
RN  - 0 (Free Radicals)
RN  - 63-84-3 (Dihydroxyphenylalanine)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Biomarkers/blood
MH  - Case-Control Studies
MH  - Chromatography, High Pressure Liquid
MH  - Dihydroxyphenylalanine/analysis/*metabolism
MH  - Female
MH  - Fluorometry
MH  - Free Radicals/analysis
MH  - Humans
MH  - Kidney Failure, Chronic/diagnosis/*therapy
MH  - Male
MH  - Middle Aged
MH  - Oxidative Stress
MH  - Probability
MH  - Prognosis
MH  - Protein Binding/*physiology
MH  - Reference Values
MH  - Renal Dialysis/*adverse effects/*methods
MH  - Risk Assessment
MH  - Sampling Studies
MH  - Statistics, Nonparametric
EDAT- 2003/12/13 05:00
MHDA- 2004/04/07 05:00
CRDT- 2003/12/13 05:00
PHST- 2003/12/13 05:00 [pubmed]
PHST- 2004/04/07 05:00 [medline]
PHST- 2003/12/13 05:00 [entrez]
AID - 10.1081/jdi-120026035 [doi]
PST - ppublish
SO  - Ren Fail. 2003 Nov;25(6):997-1009. doi: 10.1081/jdi-120026035.