Gender-specific and developmental influences on the expression of rat organic anion transporters
Gender-specific and developmental influences on the expression of rat organic anion transporters
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DOI：
10.1124/jpet.301.1.145
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发表时间：
2002-04-01
影响因子：
3.5
通讯作者：
Klaassen, CD
中科院分区：
文献类型：
--
作者：
Buist, SCN;Cherrington, NJ;Klaassen, CD
大鼠有机阴离子转运蛋白1(Oat1)、Oat2和OAT3是有机阴离子转运蛋白家族的成员，它们通过细胞膜转运一些有机阴离子。此前，Oat1和Oat3mRNA在肾脏和Oat2在肝脏中的表达最高。然而，燕麦表达的性别和发育差异仍然未知。本研究描述了不同性别和年龄的大鼠有机阴离子转运体在不同组织中的表达模式。研究了成年雄性和雌性SD大鼠肾脏组织中燕麦基因的表达，同时检测了0至45天龄SD大鼠肾脏中的发育表达。用分枝DNA信号扩增技术定量检测基因的表达。Oat1mRNA主要在肾脏中表达。令人惊讶的是，Oat2mRNA在肾脏中的表达也高于在肝脏中的表达。此外，与男性相比，女性肾脏中的燕麦2水平明显更高。最后，OAT3mRNA在肾脏中的表达最高，而在肝脏中的表达以男性为主。出生时，所有肾脏燕麦的mRNA水平都很低。在整个发育过程中，肾脏Oat1的表达逐渐增加，在30日龄时接近成年水平，在第40天和45d时，男性的Oat1水平高于女性。Oat2在肾脏中的表达在第30天时最低，但在第35天时显著增加，仅在雌性。最后，OAT3mRNA在肾脏中的表达最早成熟，从出生到10日龄迅速增加。这些数据表明，Oat mRNA的表达主要定位于肾脏，观察到的表达模式可能解释了先前发现的与化学物质暴露相关的年龄和性别相关性毒性。
Rat organic anion transporter 1 (Oat1), Oat2, and Oat3, members of the organic anion transporter family, transport some organic anions across cellular membranes. Previously, highest Oat1 and Oat3 mRNA expression was reported in kidney and Oat2 in liver. However, gender and developmental differences in Oat expression remain unknown. This study describes gender- and age-specific patterns of rat organic anion transporter expression in various tissues. Oat mRNA expression was evaluated in adult male and female Sprague-Dawley rat tissues, and developmental expression was also determined in kidneys of Sprague-Dawley rats ranging in age from days 0 through 45. Expression was quantified using branched-DNA signal amplification. Oat1 mRNA expression was primarily observed in kidney. Surprisingly, Oat2 mRNA expression was also highest in kidney rather than in liver. Moreover, considerably higher Oat2 levels were seen in female kidney as compared with male. Finally, Oat3 mRNA expression was highest in kidney of both genders, whereas a male-predominant pattern was observed in liver. At birth, all kidney Oat mRNA levels were low. Renal Oat1 expression gradually increased throughout development, approaching adult levels at 30 days of age, where at days 40 and 45 Oat1 levels were greater in males than females. Oat2 expression in kidney was minimal through day 30 but increased dramatically at day 35 in females only. Lastly, Oat3 mRNA expression in kidney matured earliest, rapidly increasing from birth through day 10. These data indicate that Oat mRNA expression is primarily localized to the kidney, and observed expression patterns may explain some previously recognized age- and gender-dependent toxicities associated with chemical exposure.