Paraoxonase and atherosclerosis-related cardiovascular diseases

In humans, three paraoxonase (PON1, PON2, and PON3) genes are clustered on chromosome 7 at a locus that spans a distance around 170 kb. These genes are highly homologous to each other and have a similar protein structural organization. PON2 is the intracellular enzyme, which is expressed in many tis...

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Bibliographic Details
Published in:Biochimie 2017-01, Vol.132, p.19-27
Main Authors: Chistiakov, Dimitry A., Melnichenko, Alexandra A., Orekhov, Alexander N., Bobryshev, Yuri V.
Format: Article
Language:English
Subjects:
Aryldialkylphosphatase - genetics
Aryldialkylphosphatase - metabolism
Atheroprotective properties
Atherosclerosis
Atherosclerosis - enzymology
Atherosclerosis - genetics
Atherosclerosis - metabolism
Cardiovascular Diseases - enzymology
Cardiovascular Diseases - genetics
Cardiovascular Diseases - metabolism
Humans
Lipoproteins, HDL - metabolism
Lipoproteins, LDL - metabolism
Models, Biological
Paraoxonase
Polymorphism, Genetic
PON1
PON2
PON3
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Summary:In humans, three paraoxonase (PON1, PON2, and PON3) genes are clustered on chromosome 7 at a locus that spans a distance around 170 kb. These genes are highly homologous to each other and have a similar protein structural organization. PON2 is the intracellular enzyme, which is expressed in many tissues and organs, while two other members of PON gene family are produced by liver and associate with high density lipoprotein (HDL). The lactonase activity is the ancestral. Besides lactones and organic phosphates, PONs can hydrolyze and therefore detoxify oxidized low density lipoprotein and homocysteine thiolactone, i.e. two cytotoxic compounds with a strong proatherogenic action. Indeed, PONs possess numerous atheroprotective properties, which include antioxidant activity, anti-inflammatory action, preserving HDL function, stimulation of cholesterol efflux, anti-apoptosis, anti-thrombosis, and anti-adhesion. PON genetic polymorphisms contribute to susceptibility/protection from atherosclerosis-related diseases. The bright antiatherogenic activity of the PON cluster makes it a promising target for the development of new therapeutic strategies. •Three human paraoxonase PON1, PON2, and PON3 genes are clustered on chromosome 7.•PONs possess numerous atheroprotective properties.•PON polymorphisms contribute to susceptibility/protection from atherosclerosis.•PON properties make PON to be a promising target for therapeutic strategies.
ISSN:0300-9084
1638-6183
DOI:10.1016/j.biochi.2016.10.010