Decreased paraoxonase-1 activity is associated with alterations of high-density lipoprotein particles in chronic liver impairment.
BACKGROUND
Paraoxonase-1 (PON1), a lactonase synthesized by the liver, circulates in blood bound to high-density lipoproteins (HDL). This enzyme is thought to degrade oxidized phospholipids and play an important role in the organism's antioxidant and anti-inflammatory system. Chronic liver diseases are characterized by decreased serum PON1 activity. The aim of the present study was to investigate the compositional changes in HDL that could influence PON1 activity in liver impairment.


METHODS
The study was performed in samples from five patients with advanced liver cirrhosis and with preserved renal function, chosen on the basis of having low serum PON1 activity and high serum PON1 concentration. As a control group, we accessed five healthy volunteers from among our hospital staff. Lipid and protein compositional analysis of lipoprotein particles were done by high-performance liquid chromatography, gel electrophoresis, and Western-Blot.


RESULTS
HDL particles from cirrhotic patients had an increased phospholipid content that was inversely correlated to PON1 activity. The HDL particles contained high levels of PON1 that corresponded, in part, to an immunoreactive protein of high molecular weight (55 kDa) not present in control subjects. This protein was identified as glycosylated PON1 and was also present in biopsies from patients with steatosis and from rats with CCl(4)-induced hepatic impairment. These changes were associated with an increased plasma concentration of markers of oxidative stress, inflammation and fibrogenesis.


CONCLUSIONS
Abnormalities in the composition of lipids and proteins of HDL particles, including PON1 glycosylation, are associated with the decrease in serum PON1 activity in patients with liver disease. These alterations may adversely affect the protective role of HDL against oxidative stress and inflammation in these patients.
Marsillach
Judit
J
Centre de Recerca Biomèdica, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, C, Sant Joan s/n, 43201 Reus, Catalunya, Spain.
Aragonès
Gerard
G
Mackness
Bharti
B
Mackness
Michael
M
Rull
Anna
A
Beltrán-Debón
Raúl
R
Pedro-Botet
Juan
J
Alonso-Villaverde
Carlos
C
Joven
Jorge
J
Camps
Jordi
J
D000818:Animals; D043303:Aryldialkylphosphatase / Q000737:chemistry / Q000378:metabolism*; D016022:Case-Control Studies; D002623:Chemistry Techniques, Analytical; D002908:Chronic Disease; D006031:Glycosylation; D006801:Humans; D007249:Inflammation; D008075:Lipoproteins, HDL / Q000032:analysis* / Q000737:chemistry; D008107:Liver Diseases / Q000378:metabolism*; D015336:Molecular Probe Techniques; D008970:Molecular Weight; D018384:Oxidative Stress; D020011:Protective Agents; D051381:Rats
D008075:Lipoproteins, HDL; D020011:Protective Agents; D043303:Aryldialkylphosphatase
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