ArticleFree radical biology & medicine2013
Gender differences in brain susceptibility to oxidative stress are mediated by levels of paraoxonase-2 expression.
Article in Free radical biology & medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 111 citations in OpenAlex.
- Oxidative Stress as a Physiological Pain Response in Full-Term Newborns.Oxidative medicine and cellular longevity · 2017Trial
- Rodent Models of Alzheimer's Disease: Bridging the Translational Gap Through Systems-Level Integration.Biomedicines · 2026Review
- Metabolic Reprogramming of Oligodendrocytes in Intrauterine Growth Restriction.Developmental neuroscience · 2026Article
- Targeting PON2 with Vutiglabridin Restores Mitochondrial Integrity and Attenuates Oxidative Stress-Induced Senescence.Antioxidants (Basel, Switzerland) · 2025Article
- Neurotherapeutic effects of Vutiglabridin as a Paraoxonase-2 modulator in preclinical models of Parkinson's disease.Molecular neurodegeneration · 2025Article
- Sex-related differences in phenotype and nigro-striatal degeneration of c-relBiology of sex differences · 2025Article
- Role of paraoxonase 2 (PON2) as a potential biomarker and therapeutic target in cancer treatment.Journal of cancer research and clinical oncology · 2025Review
- The therapeutic mechanisms of quercetin on inflammatory diseases: an update.Inflammopharmacology · 2025Review
- Targeting signaling pathways in neurodegenerative diseases: Quercetin's cellular and molecular mechanisms for neuroprotection.Animal models and experimental medicine · 2025Review
- Oxidative Stress in Brain Function.Antioxidants (Basel, Switzerland) · 2025Review
- Neuroprotective Effects of Myrtle Berry By-Product Extracts on 6-OHDA-Induced Cytotoxicity in PC12 Cells.Antioxidants (Basel, Switzerland) · 2025Article
- Neuroendocrine contribution to sex-related variations in adverse air pollution health effects.Journal of toxicology and environmental health. Part B, Critical reviews · 2024Review
- The relationship between uric acid levels, cognition and inflammation in a cohort of elderly subjects.Journal of neural transmission (Vienna, Austria : 1996) · 2024Article
- Exposure to multiple ambient air pollutants changes white matter microstructure during early adolescence with sex-specific differences.Communications medicine · 2024Article
- Brain extended and closed forms glutathione levels decrease with age and extended glutathione is associated with visuospatial memory.NeuroImage · 2024Article
- Age-associated sex difference in the expression of mitochondria-based redox sensitive proteins and effect of pioglitazone in nonhuman primate brain.Biology of sex differences · 2023Article
- Neuroprotective Effect of Vitamin D on Behavioral and Oxidative Parameters of Male and Female Adult Wistar Rats Exposed to Mancozeb (manganese/zinc ethylene bis-dithiocarbamate).Molecular neurobiology · 2023Article
- Sex and Brain: The Role of Sex Chromosomes and Hormones in Brain Development and Parkinson's Disease.Cells · 2023Review
- Associations of Particulate Matter Exposures With Brain Gray Matter Thickness and White Matter Hyperintensities: Effect Modification by Low-Grade Chronic Inflammation.Journal of Korean medical science · 2023Article
- Paraoxonases at the Heart of Neurological Disorders.International journal of molecular sciences · 2023Review
8 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Paraoxonase 2 (PON2), a member of a gene family that also includes PON1 and PON3, is expressed in most tissues, including the brain. In mouse brain, PON2 levels are highest in dopaminergic areas (e.g., striatum) and are higher in astrocytes than in neurons. PON2 is primarily located in mitochondria and exerts a potent antioxidant effect, protecting mouse CNS cells against oxidative stress. The aim of this study was to characterize PON2 expression and functions in the brains of male and female mice. Levels of PON2 (protein, mRNA, and lactonase activity) were higher in brain regions and cells of female mice. Astrocytes and neurons from male mice were significantly more sensitive (by 3- to 4-fold) to oxidative stress-induced toxicity than the same cells from female mice. Glutathione levels did not differ between genders. Importantly, no significant gender differences in susceptibility to the same oxidants were seen in cells from PON2(-/-) mice. Treatment with estradiol induced a time- and concentration-dependent increase in the levels of PON2 protein and mRNA in male (4.5-fold) and female (1.8-fold) astrocytes, which was dependent on activation of estrogen receptor-α. In ovariectomized mice, PON2 protein and mRNA were decreased to male levels in brain regions and in liver. Estradiol protected astrocytes from wild-type mice against oxidative stress-induced neurotoxicity, but did not protect cells from PON2(-/-) mice. These results suggest that PON2 is a novel major intracellular factor that protects CNS cells against oxidative stress and confers gender-dependent susceptibility to such stress. The lower expression of PON2 in males may have broad ramifications for susceptibility to diseases involving oxidative stress, including neurodegenerative diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.