Effect of non-genetic factors on paraoxonase 1 activity in patients undergoing hemodialysis.
OBJECTIVE
Hemodialyzed patients have lower paraoxonase 1 (PON1) activity. Higher mortality risk from cardiovascular disease observed in these patients could be due to the low antiathetrogenic activity of PON1. Understanding the mechanism that causes lower PON1 activity could provide the possibility for modulation of enzyme activity in purpose of preventing and/or decreasing development of atherosclerosis.


METHODS
87 healthy individuals and 71 hemodialyzed patients were enrolled in this study.


RESULTS
Hemodialyzed patients had reduced PON1 paraoxonase and arylesterase activity, concentrations of HDL, HDL(3) and HDL(2) and concentrations of free thiol groups. Distribution of HDL subfractions and distribution of PON1 phenotypes as well as concentrations of MDA were not different between two study groups. In the in vitro experiment high concentrations of urea, creatinine, uric acid and addition of patient's sera ultrafiltrate did not significantly affect PON1 paraoxonase activity.


CONCLUSIONS
Decreased HDL concentration as well as lower PON1 concentration (shown indirectly by the enzyme arylesterase activity) might contribute, at least partly, to the reduced PON1 activity observed in hemodialyzed patients. Decreased concentration of free thiol groups in sera suggest that free thiol group (Cys284) in PON1 might also be oxidized, which can affect PON1 activity.
Rajković
Marija Grdić
MG
Department of Medical Biochemistry and Hematology, University of Zagreb Faculty of Pharmacy and Biochemistry, Zagreb, Croatia. m_grdic@yahoo.com
Rumora
Lada
L
Juretić
Dubravka
D
Grubisić
Tihana Zanić
TZ
Flegar-Mestrić
Zlata
Z
Vrkić
Nada
N
Sinjeri
Zeljko
Z
Barisić
Karmela
K
D000368:Aged; D043303:Aryldialkylphosphatase / Q000235:genetics / Q000378:metabolism*; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000401:mortality; D003404:Creatinine / Q000097:blood; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000628:therapy; D008075:Lipoproteins, HDL / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D006435:Renal Dialysis / Q000009:adverse effects*; D013438:Sulfhydryl Compounds / Q000097:blood; D014508:Urea / Q000097:blood
D008075:Lipoproteins, HDL; D013438:Sulfhydryl Compounds; D008315:Malondialdehyde; D014508:Urea; D003404:Creatinine; D002265:Carboxylic Ester Hydrolases; C019734:arylesterase; D043303:Aryldialkylphosphatase