Disease relevance of Pon1

• The higher A-esterase activity with chlorpyrifos-oxon than paraoxon may be a major determinant in the observed lower acute toxicity of chlorpyrifos than parathion [1].
• Hepatic paraoxonase activity alterations and free radical production in rats with experimental cirrhosis [2].
• In spite of the technical difficulties of this study and the possible interference of the postmortem changes in the results, this article represents the first systematic approach to the characterization of human liver paraoxonase [3].
• Effects of cholesterol supplementation on antioxidant enzyme activities in rat hepatic tissues: possible implications of hepatic paraoxonase in atherogenesis [4].
• CONCLUSIONS: Our results suggest that an abnormal lipid profile and decreased PON1 activity may have a role in the pathogenesis of acute pancreatitis in which HDL-associated antioxidant defense is impaired [5].

Psychiatry related information on Pon1

• After 20 d, blood was obtained after overnight food deprivation and PON1 activity was determined [6].
• Paraoxonase 1 gene polymorphisms and dementia in humans [7].
• Light, but not heavy alcohol drinking, stimulates paraoxonase by upregulating liver mRNA in rats and humans [8].

High impact information on Pon1

• Proteins pb and ib thus seem identical with proteins p and i previously identified in rat adrenal cortex and corpus luteum (Krueger, R.J., and Orme-Johnson, N. R. (1983) J. Biol. Chem. 258, 10159-10167, and Pon, L.A., and Orme-Johnson, N.R. (1986) J. Biol. Chem. 261, 6594-6599) [9].
• RESULTS: Vitamin D-binding protein, paraoxonase, cellular retinol-binding protein, malate dehydrogenase, F-protein, and purine nucleoside phosphorylase were identified as empirically confirmed serum markers for hepatic effects in drug-treated rats [10].
• Paraoxonase (paraoxon hydrolase), an enzyme that hydrolyses paraoxon (O,O-diethyl O-p-nitrophenyl phosphate), is located in mammals primarily in the serum and liver [11].
• In addition, down-regulation of the chaperone-like protein, glucose-regulated protein 78, was consistent with the decreased expression of the secretory proteins serum paraoxonase, serum albumin, and peroxiredoxin IV [12].
• These data indicate that hyperleptinemia induced by exogenous leptin administration markedly decreases plasma PON1 activity and induces oxidative stress [13].

Chemical compound and disease context of Pon1

• Carboxylesterase and A-esterase activities during maturation and aging: relationship to the toxicity of chlorpyrifos and parathion in rats [14].
• Oxidative stress and serum paraoxonase activity in experimental hypothyroidism: effect of vitamin E supplementation [15].
• Since data on the oxidative status of hypothyroidism are limited and controversial, we investigated the oxidant and antioxidant status and serum paraoxonase/arylesterase activities in propylthiouracil-induced hypothyroidism and examined the effect of vitamin E supplementation on this experimental model [15].

Biological context of Pon1

• The purpose of the present study was to test the hypothesis that lipid peroxidation modifies the activity and protein mass of PON1 in humans and rats [16].
• The current data indicate that PON1 localization in microsomes and HDL3 could represent a selective cellular and lipoprotein response to oxidative stress [16].
• An at-'risk haplotype' could be constructed including the Gln192 and the T-107 alleles, suggesting that subjects at risk have lower plasma paraoxonase levels and this enzyme is less active [7].
• The active metabolites (oxons) of phosphorothionate insecticides can be detoxified via A-esterase hydrolysis [17].
• Plotting chlorpyrifos-oxonase activity vs paraoxonase activity for a human population using the new assay conditions provided an excellent resolution of low activity homozygotes from heterozygotes for this allele [18].

Anatomical context of Pon1

• The kinetic constants for heat inactivation evaluated for paraoxonase in rat plasma and liver microsomal fraction indicate that paraoxonase tends to inactivate faster in rat liver microsomes than in rat plasma [19].
• Similar CYP- and PON1-mediated metabolic profiles were demonstrated in microsomes from liver or isolated intestinal enterocytes [20].
• The effect of peroxisome proliferator-activated receptors alpha (PPARalpha) agonist, fenofibrate, on lipid peroxidation, total antioxidant capacity, and plasma paraoxonase 1 (PON 1) activity [21].
• Our results confirm that HDL-PON inhibited LDL oxidation, destroyed oxidized LDL, and inhibited its uptake by macrophages [8].
• On the basis of the tissue distribution observed for PON1, it is proposed that this enzyme might have a function related to the inactivation of oxidative stress by-products (either at a cellular level or blood-vessel wall) and other environmental chemicals [22].

Associations of Pon1 with chemical compounds

• Serum PON1 activity in tripalmitin-fed rats was comparable to that of controls (67 +/- 9) [6].
• Serum PON1 activity [micromol/(L.min)] was significantly (P: < 0.05) higher in triolein (98 +/- 6) and lower in fish oil (41 +/- 4), compared with tripalmitin-fed rats (63 +/- 11) [6].
• No effects of CR or gender were observed in triglyceride, total cholesterol concentration and PON1 mRNA levels [23].
• Serum and liver paraoxonase and arylesterase activities, serum triglyceride, total and HDL cholesterol concentrations, serum PON1, apoA-I and apoJ contents and liver PON1 mRNA levels were measured [23].
• Concomitant with iron-ascorbate-mediated lipid peroxidation, there was a decline in PON1 activity and protein in both HDL3 and microsomes, which was attenuated by butylated hydroxytoluene antioxidant treatment [16].

Other interactions of Pon1

• Paraoxonase 1 (PON1) associates to specific high-density lipoproteins (HDLs)--those containing apolipoprotein A-I (apoA-I) and apolipoprotein J (apoJ)--and is largely responsible for their antiatherogenic properties [23].
• Leptin decreases plasma paraoxonase 1 (PON1) activity and induces oxidative stress: the possible novel mechanism for proatherogenic effect of chronic hyperleptinemia [13].
• We conclude that prior inhibition of carboxylesterase activity impacts toxicity of subsequent exposure to PS more than CPF because of more active detoxification of CPO by A-esterase [24].
• The total esterase was further differentiated to A esterase (E.C. 1.1.2) by using E 600 (Paraoxan), and a circadian rhythm for this enzyme also has been observed [25].
• Spinal cord tissue and blood malonyldialdehyde and plasma homocysteine levels, plasma glutathione peroxidase, superoxide dismutase, paraoxonase activities were assayed [26].

Analytical, diagnostic and therapeutic context of Pon1

• Effects of caloric restriction and gender on rat serum paraoxonase 1 activity [23].
• Confirmation was obtained by the determination of PON1 expression by Western blot [16].
• The impact of two polymorphisms in PON1 (Gln192Arg associated with enzyme activity and T-107C associated with enzyme concentration) was examined in a case-control study [7].
• PON1 activity toward paraoxon, phenyl acetate, gamma-decanolactone and homogentisic acid lactone was lower in leptin-treated than in control group by 30.4, 30.8, 34.5 and 62%, respectively [13].
• In the present study, we have investigated the cellular localization of PON1 by immunohistochemistry in different rat tissues [22].

References