Effects Of Development, Age And Sex On MT And Transporter Oatp In Rat Liver And Its Significance

Objective: Metallothionein(MT) is a small, cysteine-rich, metal-binding protein that plays an important role in protecting against toxicity of heavy metals and oxidative stress. This study was aimed to examine physiological variations in m RNA levels of MT-1 and MT-2, including the development, ageing, gender, pregnancy and lactation. Methods: Livers from SD rats during development(-2, 1, 7, 14, 21, 28, 35, and 60 days) and ageing(28, 60, 180, 540 and 800 days) were collected. Total RNA was isolated, and subjected to real-time RT-PCR analysis. Results: The m RNA levels of MT-1 and MT-2 were detected in fetal livers(-2 days), slightly decreased at birth, but quickly peaked at 7 days of age. MTs were then decreased thereafter. For example, MT-1 m RNA in males decreased 10-fold at 21 days of age, and continued to decrease to 220-fold at 800 days, as compared to 7 days of age. MT-2 m RNA slightly increased at 60 days of age, then keeping decreases to 800 days of age. Males had higher MT m RNAs than females. In pregnancy and lactating rats, MT m RNAs decreased at late gestation days(GD14 and GD19). MT m RNA levels were rebound at birth, but again decreased during lactation. Conclusion: MT expression is significantly altered by physiological factors, such as the development, ageing, sex, pregnancy and lactation, which could impact the body defense against toxic stimuli and ageing.Objective: Organic anion-transporting polypeptides(Oatps) play important roles in transporting endogenous substances and xenobiotics into the liver. Many factors could influence their expression and result in changes in drug disposition. Methods: This study was aimed to examine the development-, aging-, and sex-dependent Oatps expression in livers of rats. The livers from SD rats during development(-2, 1, 7, 14, 21, 28, 35, and 60 d) and aging(28, 60, 180, 540 and/or 800 d) were collected and total RNAs were isolated, purified, and subjected to real-time PCR analysis. Total proteins were extracted for western-blot analysis. Results: It showed that Oatp1a1, Oatp1a4, Oatp1a5 and Oatp1b2 were all hardly detectable in fetal rat livers, low at birth, rapidly increased after weaning(21d), and reached the peak at 60 d. The Oatps remained stable during 60-180 d, and decreased at elderly(540 and/or 800 d). Oatp1a1, Oatp1a4, and Oatp1b2 were all highly expressed in liver, while Oatp1a5 expression was low. Oatp expressions are male-predominant in rat livers. In aged rat livers, the Oatp expression decreases and shares a consistent ontogeny pattern at the m RNA and protein level. Conclusion: This study showed that rat liver Oatp1a1, Oatp1a4, Oatp1a5 and Oatp1b2 gene expression is regulated by age and gender, which could provide a basis of individual variation in drug transport and metabolism in children and elderly.