Le Marchand Y, Patzelt C, Assimacopoulos-Jeannet F, Loten E G, Jeanrenaud B
J Clin Invest. 1974 Jun;53(6):1512-7. doi: 10.1172/JCI107701.
Livers of normal mice were prefused in situ and the secretion of newly synthesized (i.e. labeled) proteins into the perfusate were measured. In control livers, the secretion of newly synthesized proteins was found to be linear with time. In marked contrast, when livers were perfused with vinblastine, vincristine, or colchicine, drugs known to interfere with the hepatic microtubular system, the release of newly synthesized proteins was either strongly inhibited or completely suppressed although total hepatic protein synthesis (estimated by the incorporation of labeled amino acids into hepatic plus perfusate proteins) remained unaltered. Chromatographic separation of the various secreted proteins showed that the release of albumin, globulins, and small polypeptides was decreased to a similar extent by vincristine or colchicine. In the particular case of albumin, it was further observed that total (i.e. liver plus perfusate) labeled amino acid incorporation into albumin was not altered by either vincristine or colchicine, whereas the incorporation of these amino acids into liver albumin was markedly increased but incorporation into perfusate albumin was decreased, suggesting that the translocation of this particular protein from the liver to the perfusate had been affected by the presence of these drugs. It is proposed that the functional integrity of microtubules is necessary for the intracellular movement and eventual release of albumin and other proteins by the liver, and suggested that microtubules might possibly be a site of regulation of hepatic protein secretion.
对正常小鼠的肝脏进行原位预灌注，并测量新合成（即标记）蛋白质向灌注液中的分泌情况。在对照肝脏中，发现新合成蛋白质的分泌与时间呈线性关系。与之形成显著对比的是，当用长春花碱、长春新碱或秋水仙碱灌注肝脏时（这些药物已知会干扰肝脏微管系统），尽管总的肝脏蛋白质合成（通过标记氨基酸掺入肝脏和灌注液蛋白质中来估算）保持不变，但新合成蛋白质的释放要么受到强烈抑制，要么完全被抑制。对各种分泌蛋白质进行色谱分离表明，长春新碱或秋水仙碱使白蛋白、球蛋白和小多肽的释放减少到相似程度。就白蛋白而言，进一步观察到，长春新碱或秋水仙碱均未改变总的（即肝脏加灌注液）标记氨基酸掺入白蛋白的情况，然而这些氨基酸掺入肝脏白蛋白的量显著增加，但掺入灌注液白蛋白的量减少，这表明这些药物的存在影响了这种特定蛋白质从肝脏向灌注液的转运。有人提出，微管的功能完整性对于肝脏细胞内白蛋白和其他蛋白质的移动以及最终释放是必要的，并表明微管可能是肝脏蛋白质分泌的一个调节位点。
