title: Modulation of paraoxonase 2 (PON2) in mouse brain by the polyphenol quercetin: a mechanism of neuroprotection?
abstract: Quercetin is a common flavonoid polyphenol which has been shown to exert neuroprotective actions in vitro and in vivo. Though quercetin has antioxidant properties, it has been suggested that neuroprotection may be ascribed to its ability of inducing the cell's own defense mechanisms. The present study investigated whether quercetin could increase the levels of paraoxonase 2 (PON2), a mitochondrial enzyme expressed in brain cells, which has been shown to have potent antioxidant properties. PON2 protein, mRNA, and lactonase activity were highest in mouse striatal astrocytes. Quercetin increased PON2 levels, possibly by activating the JNK/AP-1 pathway. The increased PON2 levels induced by quercetin resulted in decreased oxidative stress and ensuing toxicity induced by two oxidants. The neuroprotective effect of quercetin was significantly diminished in cells from PON2 knockout mice. These findings suggest that induction of PON2 by quercetin represents an important mechanism by which this polyphenol may exert its neuroprotective action.
authors.affiliation: Department of Environmental and Occupational Health Sciences, University of Washington, 4225 Roosevelt Way NE, Suite 100, Seattle, WA 98105, USA. lgcosta@u.washington.edu
authors.forename: Lucio G
authors.initials: LG
authors.lastname: Costa
authors.forename: Leah
authors.initials: L
authors.lastname: Tait
authors.forename: Rian
authors.initials: R
authors.lastname: de Laat
authors.forename: Khoi
authors.initials: K
authors.lastname: Dao
authors.forename: Gennaro
authors.initials: G
authors.lastname: Giordano
authors.forename: Claudia
authors.initials: C
authors.lastname: Pellacani
authors.forename: Toby B
authors.initials: TB
authors.lastname: Cole
authors.forename: Clement E
authors.initials: CE
authors.lastname: Furlong
mesh_terms: D000818:Animals; D043303:Aryldialkylphosphatase / Q000378:metabolism*; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000187:drug effects* / Q000201:enzymology; D051379:Mice; D018345:Mice, Knockout; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011794:Quercetin / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018696:Neuroprotective Agents; D011794:Quercetin; D043303:Aryldialkylphosphatase