ATP合成酶β链高表达通过非清道夫受体BI途径增加原代肝细胞对高密度脂蛋白的摄取

Adenovirus mediated over expression of ATP synthase 13-chain increases high-density lipoprotein uptake in primary hepatocytes via non-SR-BI pathway

采用含人C末端标记V5tag的ATPase-B1全长的腺病毒（Ad—ATPase—B1）感染肝细胞株HepG2及清道夫受体BI（SR-BI）敲除小鼠和野生型小鼠原代肝细胞，并观察肝细胞对荧光标记物DiI标记高密度脂蛋白（HDL；DiI—HDL）的摄取情况。Ad—ATPase-B1感染HepG2和原代肝细胞后，可显著上调ATPase．B1mRNA和蛋白水平，且野生型小鼠和SR-BI。原代肝细胞Dil-HDL摄取量均明显升高（P〈0．01）。小鼠肝细胞ATPase-B1可以作为HDL的替代受体，通过非SR-BI途径增加HDL摄取。这可能是一条HDL代谢的新途径．有望作为干预HDL代谢的潜在靶点。

Recombinant adenovirus （Ad） containing the full-length human ATP synthase β-chain （ ATPase- B1 ） tagged with V5 epitope at its C-terminus was constructed and infected to HepG2 cells and primary mouse hepatocytes of wild type and SR-BI knockout mouse. Human plasma high-density lipoprotein （HDL） was prepared and labeled with fluorescent agent DiI （ 1, 1 ＇-dioctadecyl-3, 3, 3＇ 3＇-tetramethylindocarbocyanine perchlorate ） , and incubated with cultured cells. Cellular uptake of DiI-HDL was counted under a fluorescent microscope. Over expression of mRNA and protein expression of Ad-ATPase-B1 were found in HepG2 cells and primary hepatocytes. The uptake of DiI-HDL was increased in freshly-isolated hepatocytes of both wild type and SR-BI knockout mouse （ P〈0.01 ）. ATPase-B1 serves as the receptor for HDL endocytosis via non-SR-BI pathway. ATPase-β1 may represent a potential target for regulation and intervention of HDL metabolism.