The Molecular Bases of Anti-Oxidative and Anti-Inflammatory Properties of Paraoxonase 1

cris.virtual.author-orcid0000-0001-5845-4409
cris.virtualsource.author-orcid4dde7a12-8c22-4e89-9d57-7c74b050ccc5
dc.abstract.enThe 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.
dc.affiliationWydział Rolnictwa, Ogrodnictwa i Biotechnologii
dc.affiliation.instituteKatedra Biochemii i Biotechnologii
dc.contributor.authorJakubowski, Hieronim
dc.date.access2025-04-09
dc.date.accessioned2025-05-23T10:33:22Z
dc.date.available2025-05-23T10:33:22Z
dc.date.copyright2024-10-25
dc.date.issued2024
dc.description.abstract<jats:p>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.</jats:p>
dc.description.accesstimeat_publication
dc.description.additionalSpecial Issue Antioxidant Role of High-Density Lipoprotein
dc.description.bibliographyil., bibliogr.
dc.description.financepublication_nocost
dc.description.financecost0,00
dc.description.if6,0
dc.description.number11
dc.description.points100
dc.description.versionfinal_published
dc.description.volume13
dc.identifier.doi10.3390/antiox13111292
dc.identifier.issn2076-3921
dc.identifier.urihttps://sciencerep.up.poznan.pl/handle/item/2810
dc.identifier.weblinkhttps://www.mdpi.com/2076-3921/13/11/1292
dc.languageen
dc.relation.ispartofAntioxidants
dc.relation.pagesart. 1292
dc.rightsCC-BY
dc.sciencecloudnosend
dc.share.typeOPEN_JOURNAL
dc.subject.enPON1 physiological substrates
dc.subject.enhomocysteine thiolactone
dc.subject.en5-(3′
dc.subject.en4′-dihydroxyphenyl)-γ- valerolactone
dc.subject.enPON1 proteomics
dc.subject.enanti-oxidant proteins
dc.subject.enanti-inflammatory proteins
dc.subject.encardiovascular disease
dc.subject.enAlzheimer’s disease
dc.subject.encancer
dc.titleThe Molecular Bases of Anti-Oxidative and Anti-Inflammatory Properties of Paraoxonase 1
dc.typeJournalArticle
dspace.entity.typePublication
oaire.citation.issue11
oaire.citation.volume13