Pharmacogenetics of paraoxonases: a brief review

@article{Draganov2004PharmacogeneticsOP,
  title={Pharmacogenetics of paraoxonases: a brief review},
  author={Dragomir I Draganov and Bert N. La Du},
  journal={Naunyn-Schmiedeberg's Archives of Pharmacology},
  year={2004},
  volume={369},
  pages={78-88}
}
  • D. Draganov, B. La Du
  • Published 2004
  • Biology, Medicine
  • Naunyn-Schmiedeberg's Archives of Pharmacology
The human paraoxonase (PON) gene family consists of three members, PON1, PON2, and PON3, aligned next to each other on chromosome 7. By far the most-studied member of the family is the serum paraoxonase 1 (PON1), a high-density lipoprotein-associated esterase/lactonase. Early research focused on its capability to hydrolyze toxic organophosphates, and its name derives from one of its most commonly used in vitro substrates, paraoxon. Studies in the last 2 decades have demonstrated PON1’s ability… Expand
The human paraoxonase gene cluster as a target in the treatment of atherosclerosis.
TLDR
Evidence is provided that the PON cluster is a prospective target for the treatment of atherosclerosis and clinical observations focusing on gene polymorphisms indicate that PON1, PON2, and PON3 are protective against coronary artery disease. Expand
The Role of Paraoxonase in Cardiovascular Diseases
TLDR
There is a certain relation between PON1 polymorphism and HDL and LDL particles, and the PON1192RR genotype is associated with lower HDL levels and higher LDL levels. Expand
CHAPTER 67 – Paraoxonase (PON1) and Detoxication of Nerve Agents
Publisher Summary PON1 is a member of a family of proteins that also includes PON2 and PON3, the genes of which are clustered in tandem on the long arms of human chromosome 7 (q21.22). ParaoxonaseExpand
Human paraoxonase 2
TLDR
The number of investigations concerning the relationship between two common PON2 polymorphisms and CVD among different ethnic groups and regions is rapidly growing and emerging evidence has proposed that Pon2 is an anti-atherosclerotic and may be associated with cardiovascular disease (CVD). Expand
Paraoxonase, a cardioprotective enzyme: continuing issues
TLDR
PON1 mass and activity in the plasma significantly influence the risk of developing cardiovascular disease and the role of PON2 and PON3 in atherosclerosis and their antioxidant properties with respect to LDL and macrophages also merit further investigation. Expand
Paraoxonase and atherosclerosis-related cardiovascular diseases.
TLDR
The bright antiatherogenic activity of the PON cluster makes it a promising target for the development of new therapeutic strategies, which include antioxidant activity,Anti-inflammatory action, preserving HDL function, stimulation of cholesterol efflux, anti-apoptosis, anti -thrombosis, and anti-adhesion. Expand
Paraoxonases-1, -2 and -3: What are their functions?
TLDR
Both PON2 and PON3 are upregulated in cancer, favoring tumor progression through mitochondrial protection against oxidative stress and apoptosis, and both are susceptible to obesity, gallstone formation and atherosclerosis. Expand
Structure-reactivity studies of serum paraoxonase PON1 suggest that its native activity is lactonase.
PON1 is the best-studied member of a family of enzymes called serum paraoxonases, or PONs, identified in mammals (including humans) and other vertebrates as well as in invertebrates. PONs exhibit aExpand
Determination of Paraoxonase 1 Status Without the Use of Toxic Organophosphate Substrates
TLDR
Paraoxonase 1 is a member of a tandem 3-gene family localized on human chromosome 7q21-22 and was initially characterized and named for its ability to hydrolyze paraoxon, the toxic oxon metabolite of parathion. Expand
Paraoxonase 1 (PON1) as a genetic determinant of susceptibility to organophosphate toxicity.
TLDR
Evidence is slowly emerging that a low PON1 status may increase susceptibility to OP toxicity in humans, as shown by animal and human studies. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 102 REFERENCES
Paraoxonase genes and disease.
  • R. Hegele
  • Biology, Medicine
  • Annals of medicine
  • 1999
TLDR
Emerging evidence from biochemical and genetic experiments is providing clues about the role(s) of the products of these genes, including PON1, PON2 and PON3, which are located on chromosome 7q21.3-22.1. Expand
The human serum paraoxonase/arylesterase gene (PON1) is one member of a multigene family.
TLDR
Evidence that the human genome contains two PON1-like genes, designated PON2 and PON3, is presented here and will have important implications for future experiments designed to discover the individual functions, catalytic properties, and physiological roles of the paraoxonases. Expand
Determination of paraoxonase (PON1) status requires more than genotyping.
TLDR
A two-dimensional, microtitre plate reader-based enzyme analysis that provides a high-throughput assessment of PON1 status and an accurate inference of Pon1 genotype is reported here. Expand
Effects of 5' regulatory-region polymorphisms on paraoxonase-gene (PON1) expression.
TLDR
The results presented here indicate that the L55M effect of lowered activity is not due to the amino acid change but is, rather, largely due to linkage disequilibrium with the -108 regulatory-region polymorphism. Expand
Polymorphisms in the human paraoxonase (PON1) promoter.
TLDR
A deletion analysis of the PON1 promoter region in transient transfection assays found that cell-type specific promoter elements for liver and kidney are present in the first 200bp upstream of the coding sequence. Expand
Promoter polymorphisms of human paraoxonase PON1 gene and serum paraoxonase activities and concentrations.
  • I. Leviev, R. James
  • Biology, Medicine
  • Arteriosclerosis, thrombosis, and vascular biology
  • 2000
TLDR
A genetic basis for variations in serum Pon levels and, consequently, serum PON activity is firmly established, consistent with the suggestion that variations in a major antioxidant function of high density lipoprotein are, to an important degree, genetically determined. Expand
On the physiological role(s) of the paraoxonases.
TLDR
This Third International Meeting on Esterases Reacting with Organophosphorus Compounds focuses on the organophosphatase activities of paraoxonase and related enzymes and it is important to also briefly review some of the current directions in several laboratories searching for additional functions of the paraox onases to extend the understanding of the properties of this family of enzymes. Expand
Does paraoxonase play a role in susceptibility to cardiovascular disease?
  • M. Aviram
  • Biology, Medicine
  • Molecular medicine today
  • 1999
TLDR
Experimental studies suggest that protection against atherosclerosis is associated with the ability of PON1 to hydrolyze specific lipid peroxides in oxidized lipoproteins, and interventions that preserve or enhance PON 1 activity, as well as manipulations of Pon1 polymorphisms, might help delay the onset of CHD. Expand
Decreased stability of the M54 isoform of paraoxonase as a contributory factor to variations in human serum paraoxonase concentrations.
TLDR
Evidence is provided for lesser stability of the M54 isoform of PON, apparently involving greater susceptibility to proteolysis and implications for the antioxidant capacity of HDL. Expand
Paraoxonase Status in Coronary Heart Disease: Are Activity and Concentration More Important Than Genotype?
TLDR
It is found that lower PON1 activity and concentration and, therefore, the reduced ability to prevent LDL lipid peroxidation may be more important in determining the presence of CHD than paraoxonase genetic polymorphisms. Expand
...
1
2
3
4
5
...