Leptin-derived peptide, a targeting ligand for mouse brain-derived endothelial cells via macropinocytosis.
Leptin-derived peptide, a targeting ligand for mouse brain-derived endothelial cells via macropinocytosis.
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DOI：
10.1016/j.bbrc.2010.03.024
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发表时间：
2010-04
影响因子：
3.1
通讯作者：
Mina Tamaru;H. Akita;T. Fujiwara;Kazuaki Kajimoto;H. Harashima
中科院分区：
文献类型：
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作者：
Mina Tamaru;H. Akita;T. Fujiwara;Kazuaki Kajimoto;H. Harashima
瘦素是一种食欲调节激素，由脂肪组织分泌到血液循环中，并通过穿过血脑屏障（BBB）在中枢神经系统（即下丘脑）中发挥作用。在本研究中，我们研究了瘦素衍生肽（Lep 70 -89）作为小鼠脑源性内皮细胞（MBEC 4）的配体的功能。用聚乙二醇（PEG）间隔物制备的Lep 70 -89修饰的脂质体（Lep 70 -89-PEG-LP）表现出比肽未修饰的脂质体（PEG-LP）显著更高的细胞摄取。此外，阿米洛利抑制细胞摄取，而氯丙嗪和菲律宾III的存在下，没有观察到显着的抑制作用，表明巨胞饮在很大程度上有助于细胞摄取Lep 70 -89-PEG-LP。成像研究表明，Lep 70 -89-PEG-LP并未与核内体/溶酶体共定位，而中性右旋糖酐（70 kDa）主要与这些隔室共定位。这表明Lep 70 -89-PEG-LP通过巨胞饮作用被摄取，并进行非经典的细胞内运输，从而避免了内皮细胞中的溶酶体降解。
Leptin is an appetite regulatory hormone that is secreted into the blood circulation by adipose tissue, and functions in the central nerve system (i.e. hypothalamus) by crossing the blood brain barrier (BBB). In the present study, we investigated the function of a leptin-derived peptide (Lep70–89) as a ligand for mouse brain-derived endothelial cells (MBEC4). Lep70–89-modified liposomes, prepared with a polyethyleneglycol (PEG) spacer (Lep70–89-PEG-LPs) exhibited a significantly higher cellular uptake than peptide-unmodified liposomes (PEG-LPs). Furthermore, cellular uptake was inhibited by amiloride, while no significant inhibitory effect was observed by the presence of chlorpromazine and filipin III, suggesting that macropinocytosis largely contributed to the cellular uptake of Lep70–89-PEG-LPs. Imaging studies revealed that Lep70–89-PEG-LPs were not colocalized with endosome/lysosomes, whereas neutral dextran (70kDa) was predominantly colocalized with these compartments. This indicates that Lep70–89-PEG-LPs are taken up via macropinocytosis and are subject to non-classical intracellular trafficking, resulting in the circumvention of lysosomal degradation in endothelial cells.