PON2
Serum paraoxonase/arylesterase 2 (EC 3.1.1.2) (EC 3.1.1.81) (PON 2) (Aromatic esterase 2) (A-esterase 2) (Serum aryldialkylphosphatase 2)
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A Mediterranean diet rich in olive oil has been associated with health benefits in humans. It is unclear if and to what extent olive oil phenolics may mediate these health benefits. In this study, we fed senescence-accelerated mouse-prone 8 (SAMP8, n=11 per group) semisynthetic diets with 10% olive oil containing either high (HP) or low amounts of olive oil phenolics (LP) for 4.5 months. Mice consuming the HP diet had significantly lower concentrations of the oxidative damage markers thiobarbituric acid-reactive substances and protein carbonyls in the heart, whereas proteasomal activity was similar in both groups. Nrf2-dependent gene expression may be impaired during the aging process. Therefore, we measured Nrf2 and its target genes glutathione-S-transferase (GST), γ-glutamyl cysteine synthetase (γ-GCS), nicotinamide adenine dinucleotide phosphate [NAD(P)H]:quinone oxidoreductase (NQO1), and paraoxonase-2 (PON2) in the hearts of these mice. Nrf2 as well as GST, γ-GCS, NQO1, and PON2 mRNA levels were significantly higher in heart tissue of the HP as compared to the LP group. The HP-fed mice had significantly higher PON1 activity in serum compared to those receiving the LP diet. Furthermore, HP feeding increased relative SIRT1 mRNA levels. Additional mechanistic cell culture experiments were performed, and they suggest that the olive oil phenolic hydroxytyrosol present in the HP oil may be responsible for the induction of Nrf2-dependent gene expression and the increase in PON activity. In conclusion, a diet rich in olive oil phenolics may prevent oxidative stress in the heart of SAMP8 mice by modulating Nrf2-dependent gene expression.
MeSH Terms
- Aging
- Animal Feed
- Animals
- Antioxidants
- Cellular Senescence
- Female
- Gene Expression Regulation
- Iron
- Lipid Peroxidation
- Mice
- Myocardium
- NF-E2-Related Factor 2
- Olive Oil
- Oxidants
- Oxidative Stress
- Phenol
- Plant Oils
- Spectrophotometry
Paraoxonase 1 (PON1) is a high-density lipoprotein-associated enzyme that is believed to be involved in the protection against oxidative stress. There is evidence that paraoxonase activity is reduced in patients with diabetes and cataract. In the current study, we analyzed mRNA expression of PON1 as well as other members of the paraoxonase family, PON2 and PON3, in human cataractous lens samples. Our results indicate that only PON1 is expressed at the gene and protein levels in human lens tissues. We quantified MDA levels and measured PON1 (paraoxonase/arylesterase) enzymatic activities in subjects suffering from cataract due to aging and diabetes. Decreased PON1 activity was more pronounced in diabetic patients (p< 0.001) compared to senile subjects, which may be due to glycation and increased oxidative insult. To examine the structural alterations that occur in response to glycation, we constructed a three-dimensional model of PON1 and its glycated variant. Glycation at Lys70 and Lys75 is predicted to cause hindrance in binding of substrate to the active site of the enzyme.
MeSH Terms
- Aged
- Aging
- Aryldialkylphosphatase
- Cataract
- Diabetes Mellitus, Type 2
- Esterases
- Female
- Gene Expression Regulation
- Glycation End Products, Advanced
- Humans
- Immunohistochemistry
- Lens, Crystalline
- Lipid Peroxidation
- Male
- Malondialdehyde
- Middle Aged
- Models, Chemical
- Oxidative Stress
- Substrate Specificity