title: Age- and sex-related differences of organic anion-transporting polypeptide gene expression in livers of rats.
abstract: Organic anion-transporting polypeptides (Oatps) play important roles in transporting endogenous substances and xenobiotics into the liver and are implicated in drug-drug interactions. Many factors could influence their expression and result in alterations in drug disposition, efficacy and toxicity. 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 (60, 180, 540 and/or 800 d) were collected and total RNAs were extracted, purified, and subjected to real-time PCR analysis. Total proteins were extracted for western-blot analysis. Results showed that Oatp1a1, Oatp1a4, Oatp1a5 and Oatp1b2 were all hardly detectable in fetal rat livers, low at birth, rapidly increased after weaning (21 d), and reached the peak at 60 d. The Oatps remained stable during the age between 60-180 d, and decreased at elderly (540 and/or 800 d). After birth, Oatp1a1, Oatp1a4, and Oatp1b2 were all highly expressed in liver, in contrast, Oatp1a5 expression was low. Oatp expressions are male-predominant in rat livers. In the livers of aged rats, the Oatp expression decreased and shared a consistent ontogeny pattern at the mRNA and protein level. In conclusion, this study showed that in rat liver, Oatp1a1, Oatp1a4, Oatp1a5 and Oatp1b2 gene expressions are influenced by age and gender, which could provide a basis of individual variation in drug transport, metabolism and toxicity in children, elderly and women.
authors.affiliation: Key Lab for Pharmacology of Ministry of Education, Zunyi Medical College, Zunyi 563003, China.
authors.forename: Wei-Yu
authors.initials: WY
authors.lastname: Hou
authors.affiliation: Key Lab for Pharmacology of Ministry of Education, Zunyi Medical College, Zunyi 563003, China.
authors.forename: Shang-Fu
authors.initials: SF
authors.lastname: Xu
authors.affiliation: Key Lab for Pharmacology of Ministry of Education, Zunyi Medical College, Zunyi 563003, China.
authors.forename: Qiong-Ni
authors.initials: QN
authors.lastname: Zhu
authors.affiliation: Key Lab for Pharmacology of Ministry of Education, Zunyi Medical College, Zunyi 563003, China.
authors.forename: Yuan-Fu
authors.initials: YF
authors.lastname: Lu
authors.affiliation: Department of Pharmaceutical Sciences, St. John's University, New York, NY 11439, USA.
authors.forename: Xing-Guo
authors.initials: XG
authors.lastname: Cheng
authors.affiliation: Key Lab for Pharmacology of Ministry of Education, Zunyi Medical College, Zunyi 563003, China. Electronic address: Jieliu@zmc.edu.cn.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
mesh_terms: D000367:Age Factors; D000375:Aging / Q000378:metabolism; D000818:Animals; D005333:Fetus / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D027361:Organic Anion Transporters / Q000235:genetics*; D029362:Organic Anion Transporters, Sodium-Independent / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3
chemical_list: D027361:Organic Anion Transporters; D029362:Organic Anion Transporters, Sodium-Independent; D012333:RNA, Messenger; C503597:Slco1a4 protein, rat; C421143:Slco1a5 protein, rat; C421207:Slco1b2 protein, rat; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3
keywords: Aging; Development; Gene expression; Oatps; Rat liver; Sex-difference