ABC transporter (P-gp/ABCB1, MRP1/ABCC1, BCRP/ABCG2) expression in the developing human CNS.
ABC transporter (P-gp/ABCB1, MRP1/ABCC1, BCRP/ABCG2) expression in the developing human CNS.
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DOI：
10.1055/s-0028-1103272
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发表时间：
2008-08
期刊：
影响因子：
1.4
通讯作者：
Watchko JF
中科院分区：
文献类型：
--
作者：
Daood M;Tsai C;Ahdab-Barmada M;Watchko JF
P-糖蛋白（P-gp/ABCB 1）、多药耐药蛋白1（MRP 1/ABCC 1）和乳腺癌耐药蛋白（BCRP/ABCG 2）是限制细胞内大量亲脂性、两亲性异种和内生菌摄取和保留的质膜外排泵。P-gp/ABCB 1、MRP 1/ABCC 1和BCRP/ABCG 2在人类中枢神经系统（CNS）中的新生儿和发育表达知之甚少，因此，对妊娠220/7- 420/7周出生的婴儿和成人的死后CNS组织进行免疫染色，以确定其个体发育和细胞定位。早在220/7周时，在微血管内皮细胞中观察到P-gp/ABCB 1免疫染色，随着成熟，患病率和强度增加，妊娠后期在大锥体神经元中观察到P-gp/ABCB 1免疫染色。MRP 1/ABCC 1免疫染色在脉络丛和室管膜早期突出，随后在大锥体神经元中注意到。BCRP/ABCG 2表达仅限于微血管内皮细胞。P-gp/ABCB 1、MRP 1/ABCC 1和BCRP/ABCG 2在成人脑组织中与足月新生儿CNS相匹配，但免疫染色更强。我们的结论是，P-gp/ABCB 1，MRP 1/ABCC 1，和BCRP/ABCG 2的表达在一个发展，细胞特异性，在人类中枢神经系统的方式。血脑中P-gp/ABCB 1和BCRP/ABCG 2与血-CSF屏障中MRP 1/ABCC 1的互补模式可能限制新生儿CNS对药物和毒素的摄取和保留。
P-glycoprotein (P-gp/ABCB1), multidrug resistance protein 1 (MRP1/ABCC1), and breast cancer resistance protein (BCRP/ABCG2) are plasma membrane efflux pumps that limit the intracellular uptake and retention of numerous lipophilic, amphipathic xeno- and endobiotics. Little is known about the neonatal and developmental expression of P-gp/ABCB1, MRP1/ABCC1, and BCRP/ABCG2 in the human central nervous system (CNS), therefore postmortem CNS tissue from infants born 220/7- 420/7 week gestation and adults was immunostained to determine their ontogeny and cellular localization. P-gp/ABCB1 imunostaining was observed in microvessel endothelial cells as early as 220/7 weeks, increasing in prevalence and intensity with maturation, and later in gestation in large pyramidal neurons. MRP1/ABCC1 immunostaining was prominent early in the choroid plexus and ventricular ependyma, and noted later in large pyramidal neurons. BCRP/ABCG2 expression was limited to microvessel endothelial cells. P-gp/ABCB1, MRP1/ABCC1 and BCRP/ABCG2 in adult brain matched term newborn CNS but with more intense immunostaining. We conclude that P-gp/ABCB1, MRP1/ABCC1, and BCRP/ABCG2 are expressed in a developmental, cell specific, fashion in the human CNS. The complementary pattern of P-gp/ABCB1 and BCRP/ABCG2 at the blood-brain with MRP1/ABCC1 at the blood-CSF barriers may limit CNS uptake and retention of drugs and toxins in neonates.
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DOI：
10.1016/0005-2736(93)90083-c
发表时间：
1993-08-15
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
JETTE, L;TETU, B;BELIVEAU, R
通讯作者：
BELIVEAU, R
影响因子：
3.3
作者：
Nies, AT;Jedlitschky, G;Keppler, D
通讯作者：
Keppler, D
影响因子：
2.4
作者：
Ginn, PE
通讯作者：
Ginn, PE
影响因子：
3.8
作者：
Lazarowski, A;Lubieniecki, F;Taratuto, AL
通讯作者：
Taratuto, AL
影响因子：
7.3
作者：
Diestra, JE;Scheffer, GL;Izquierdo, MA
通讯作者：
Izquierdo, MA