title: Developmental expression of paraoxonase 2.
abstract: Paraoxonase 2 (PON2) is a member of the paraoxonase gene family also comprising PON1 and PON3. PON2 functions as a lactonase and exhibits anti-bacterial as well as antioxidant properties. At the cellular level, PON2 localizes to the mitochondrial and endoplasmic reticulum membranes where it scavenges reactive oxygen species. PON2 is of particular interest as it is the only paraoxonase expressed in brain tissue and appears to play a critical role in mitigating oxidative stress in the brain. The aim of this study was to investigate the expression of PON2 at the protein and mRNA level in the brain and liver of mice through development to identify potential age windows of susceptibility to oxidative stress, as well as to compare expression of hepatic PON2 to expression of PON1 and PON3. Overall, PON2 expression in the brain was lower in neonatal mice and increased with age up to postnatal day (PND) 21, with a significant decrease observed at PND 30 and 60. In contrast, the liver showed continuously increasing levels of PON2 with age, similar to the patterns of PON1 and PON3. PON2 protein levels were also investigated in brain samples from non-human primates, with PON2 increasing with age up to the infant stage and decreasing at the juvenile stage, mirroring the results observed in the mouse brain. These variable expression levels of PON2 suggest that neonatal and young adult animals may be more susceptible to neurological insult by oxidants due to lower levels of PON2 in the brain.
authors.affiliation: Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, United States. Electronic address: jacqueg@u.washington.edu.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Garrick
authors.affiliation: Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, United States.
authors.forename: Khoi
authors.initials: K
authors.lastname: Dao
authors.affiliation: Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, United States.
authors.forename: Rian
authors.initials: R
authors.lastname: de Laat
authors.affiliation: Department of Psychiatry, Yale University, New Haven, CT, United States.
authors.forename: John
authors.initials: J
authors.lastname: Elsworth
authors.affiliation: Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, United States; Center on Human Development and Disabilities, University of Washington, United States.
authors.forename: Toby B
authors.initials: TB
authors.lastname: Cole
authors.affiliation: Depts. of Medicine (Div. Medical Genetics) and of Genome Sciences, University of Washington, United States.
authors.forename: Judit
authors.initials: J
authors.lastname: Marsillach
authors.affiliation: Depts. of Medicine (Div. Medical Genetics) and of Genome Sciences, University of Washington, United States.
authors.forename: Clement E
authors.initials: CE
authors.lastname: Furlong
authors.affiliation: Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, United States; Dept. of Neuroscience, University of Parma, Italy.
authors.forename: Lucio G
authors.initials: LG
authors.lastname: Costa
mesh_terms: D000818:Animals; D043303:Aryldialkylphosphatase / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D000882:Haplorhini; D015151:Immunoblotting; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D012333:RNA, Messenger; D043303:Aryldialkylphosphatase; C560866:PON3 protein, mouse
keywords: Brain; Development; Liver; Oxidative stress; Paraoxonase 1; Paraoxonase 2; Paraoxonase 3