Ontogeny and aging of Nrf2 pathway genes in livers of rats

The Nrf2/Keap1 antioxidant system plays important roles in protecting against oxidative stress and toxic stimuli, which may vary in infants, elderly, and females. The constitutive expression of the Nrf2 genes during development and aging in both sexes would help our understanding of the Nrf2/Keap1 pathway in toxicological studies. Sprague Dawley rat livers were collected at 11 age points from prenatal (−2 d), neonatal (1, 7, 14 and 21 d), at puberty (28 and 35 d), at adulthood (60 and 180 d), to aging (540 and 800 d) from both sexes. Total RNA and proteins were extracted for real-time RT-PCR and Western-blot analysis. The abundant mRNA expression was in the order of Nrf2, Gclm, Nqo1, Gclc, Ho-1, and Keap1. The expression of these genes except Gclc was high in fetal livers, decreased at birth, reached the first peak at 7 days of age, and gradually decreased to adult levels till 180 days of age. All these genes remained high at 540 days of age, but declined at 800 days of age, with more increases with Nqo1 and Ho-1. Females had lower fetal, neonatal, and aged levels than males. Protein expressions of Nrf2, Nqo1, Ho-1, GCLC and GCLM agree with mRNA analysis. This study characterized the age- and sex-related changes of Nrf2-related gene/proteins in livers of rats, and higher expressions in newborns and aged rats could cope with increased oxidative stress in infants and elderly.