L-Carnitine transport in human placental brush-border membranes is mediated by the sodium-dependent organic cation transporter OCTN2
L-Carnitine transport in human placental brush-border membranes is mediated by the sodium-dependent organic cation transporter OCTN2
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DOI：
10.1152/ajpcell.00333.2003
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发表时间：
2004-08-01
影响因子：
5.5
通讯作者：
Mitchell, GA
中科院分区：
文献类型：
--
作者：
Lahjouji, K;Elimrani, I;Mitchell, GA
L肉碱是一种将长链脂肪酸运送到线粒体进行氧化的分子，其母胎转运被认为对胎儿为产后高脂牛奶饮食做好准备具有重要作用。利用人足月胎盘刷状缘膜囊泡，我们发现L-卡尼汀的摄取是钠和温度依赖性的，对卡尼汀表现出很高的亲和力(表观K-m=11.09+/-1.32um；V-max=41.75+/-0.94pmol.mg蛋白(-1).min(-1))，在pH 5.5-8.5范围内不变。丙戊酸盐、维拉帕米、四乙基铵和吡拉胺以及L肉碱的结构类似物D-肉碱、乙酰基-D、L-肉碱、丙酰、丁酰基、辛酰基、异戊基和棕榈酰基-L肉碱均能抑制BBM囊泡摄取L肉碱。Western印迹分析表明，OCTN2是一种高亲和力、钠离子依赖的肉碱转运蛋白，存在于胎盘BBM中，但不存在于分离的基底膜囊泡中。已报道的OCTN_2的性质与观察到的胎盘BBM囊泡摄取L肉碱的特性相似，提示OCTN_2可能介导了大多数母胎肉碱在人类体内的转运。
Maternofetal transport of L-carnitine, a molecule that shuttles long-chain fatty acids to the mitochondria for oxidation, is thought to be important in preparing the fetus for its lipid-rich postnatal milk diet. Using brush-border membrane (BBM) vesicles from human term placentas, we showed that L-carnitine uptake was sodium and temperature dependent, showed high affinity for carnitine (apparent K-m = 11.09 +/- 1.32 muM; V-max = 41.75 +/- 0.94 pmol.mg protein(-1).min(-1)), and was unchanged over the pH range from 5.5 to 8.5. L-Carnitine uptake was inhibited in BBM vesicles by valproate, verapamil, tetraethylammonium, and pyrilamine and by structural analogs of L-carnitine, including D-carnitine, acetyl-D, L-carnitine, and propionyl-, butyryl-, octanoyl, isovaleryl-, and palmitoyl-L-carnitine. Western blot analysis revealed that OCTN2, a high-affinity, Na+-dependent carnitine transporter, was present in placental BBM but not in isolated basal plasma membrane vesicles. The reported properties of OCTN2 resemble those observed for L-carnitine uptake in placental BBM vesicles, suggesting that OCTN2 may mediate most maternofetal carnitine transport in humans.