The Molecular Bases of Anti-Oxidative and Anti-Inflammatory Properties of Paraoxonase 1
The anti-oxidative and anti-inflammatory properties of high-density lipoprotein (HDL) are thought to be mediated by paraoxonase 1 (PON1), a calcium-dependent hydrolytic enzyme carried on a subfraction of HDL that also carries other anti-oxidative and anti-inflammatory proteins. In humans and mice, l...
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MDPI AG
2024-10-01
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| Series: | Antioxidants |
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| author | Hieronim Jakubowski |
| author_facet | Hieronim Jakubowski |
| author_sort | Hieronim Jakubowski |
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| description | The anti-oxidative and anti-inflammatory properties of high-density lipoprotein (HDL) are thought to be mediated by paraoxonase 1 (PON1), a calcium-dependent hydrolytic enzyme carried on a subfraction of HDL that also carries other anti-oxidative and anti-inflammatory proteins. In humans and mice, low PON1 activity is associated with elevated oxidized lipids and homocysteine (Hcy)-thiolactone, as well as proteins that are modified by these metabolites, which can cause oxidative stress and inflammation. PON1-dependent metabolic changes can lead to atherothrombotic cardiovascular disease, Alzheimer’s disease, and cancer. The molecular bases underlying these associations are not fully understood. Biochemical, proteomic, and metabolic studies have significantly expanded our understanding of the mechanisms by which low PON1 leads to disease and high PON1 is protective. The studies discussed in this review highlight the changes in gene expression affecting proteostasis as a cause of the pro-oxidative and pro-inflammatory phenotypes associated with attenuated PON1 activity. Accumulating evidence supports the conclusion that PON1 regulates the expression of anti-oxidative and anti-inflammatory proteins, and that the disruption of these processes leads to disease. |
| format | Article |
| id | doaj-art-fa0e35e6de1c40cd91b60258f1f8c74c |
| institution | OA Journals |
| issn | 2076-3921 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | MDPI AG |
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| series | Antioxidants |
| spelling | doaj-art-fa0e35e6de1c40cd91b60258f1f8c74c2025-08-20T02:26:54ZengMDPI AGAntioxidants2076-39212024-10-011311129210.3390/antiox13111292The Molecular Bases of Anti-Oxidative and Anti-Inflammatory Properties of Paraoxonase 1Hieronim Jakubowski0Department of Biochemistry and Biotechnology, University of Life Sciences, 60-637 Poznań, PolandThe anti-oxidative and anti-inflammatory properties of high-density lipoprotein (HDL) are thought to be mediated by paraoxonase 1 (PON1), a calcium-dependent hydrolytic enzyme carried on a subfraction of HDL that also carries other anti-oxidative and anti-inflammatory proteins. In humans and mice, low PON1 activity is associated with elevated oxidized lipids and homocysteine (Hcy)-thiolactone, as well as proteins that are modified by these metabolites, which can cause oxidative stress and inflammation. PON1-dependent metabolic changes can lead to atherothrombotic cardiovascular disease, Alzheimer’s disease, and cancer. The molecular bases underlying these associations are not fully understood. Biochemical, proteomic, and metabolic studies have significantly expanded our understanding of the mechanisms by which low PON1 leads to disease and high PON1 is protective. The studies discussed in this review highlight the changes in gene expression affecting proteostasis as a cause of the pro-oxidative and pro-inflammatory phenotypes associated with attenuated PON1 activity. Accumulating evidence supports the conclusion that PON1 regulates the expression of anti-oxidative and anti-inflammatory proteins, and that the disruption of these processes leads to disease.https://www.mdpi.com/2076-3921/13/11/1292PON1 physiological substrateshomocysteine thiolactone5-(3′,4′-dihydroxyphenyl)-γ-valerolactonePON1 proteomicsanti-oxidant proteinsanti-inflammatory proteins |
| spellingShingle | Hieronim Jakubowski The Molecular Bases of Anti-Oxidative and Anti-Inflammatory Properties of Paraoxonase 1 Antioxidants PON1 physiological substrates homocysteine thiolactone 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone PON1 proteomics anti-oxidant proteins anti-inflammatory proteins |
| title | The Molecular Bases of Anti-Oxidative and Anti-Inflammatory Properties of Paraoxonase 1 |
| title_full | The Molecular Bases of Anti-Oxidative and Anti-Inflammatory Properties of Paraoxonase 1 |
| title_fullStr | The Molecular Bases of Anti-Oxidative and Anti-Inflammatory Properties of Paraoxonase 1 |
| title_full_unstemmed | The Molecular Bases of Anti-Oxidative and Anti-Inflammatory Properties of Paraoxonase 1 |
| title_short | The Molecular Bases of Anti-Oxidative and Anti-Inflammatory Properties of Paraoxonase 1 |
| title_sort | molecular bases of anti oxidative and anti inflammatory properties of paraoxonase 1 |
| topic | PON1 physiological substrates homocysteine thiolactone 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone PON1 proteomics anti-oxidant proteins anti-inflammatory proteins |
| url | https://www.mdpi.com/2076-3921/13/11/1292 |
| work_keys_str_mv | AT hieronimjakubowski themolecularbasesofantioxidativeandantiinflammatorypropertiesofparaoxonase1 AT hieronimjakubowski molecularbasesofantioxidativeandantiinflammatorypropertiesofparaoxonase1 |