Walker P R, Whitfield J F
Proc Natl Acad Sci U S A. 1978 Mar;75(3):1394-8. doi: 10.1073/pnas.75.3.1394.
The uptake of amino acids (measured with alpha-aminoisobutyric acid) by hepatocytes stimulated to proliferate by partial hepatectomy followed a biphasic pattern, with an initial peak 8-10 hr after surgery followed by a release of amino acids between 10 and 16 hr and a further increase between 16 and 20 hr after the operation. The second period of increased uptake coincided with the increase in DNA synthesis by the hepatocytes. Colchicine, and other microtubule disrupters administered at the time of partial hepatectomy, abolished the first period of increased amino acid uptake and prevented the cells from initiating DNA synthesis. Pulse-labeling experiments with alpha-aminoisobutyric acid revealed that colchicine did not inhibit amino acid transport per se, but prevented the increased capacity for amino acid transport induced by partial hepatectomy. An injection of colchicine 14 hr after hepatectomy prevented the release of amino acids by the liver and also substantially reduced the initiation of DNA synthesis. The data suggest that the microtubules may play a role in proliferative activation and also in the initiation of DNA synthesis of hepatocytes in vivo and that changes in amino acid transport are linked to these microtubule-requiring processes.
用α-氨基异丁酸测量，部分肝切除刺激肝细胞增殖后对氨基酸的摄取呈双相模式，术后8 - 10小时出现初始峰值，随后在10至16小时之间氨基酸释放，术后16至20小时进一步增加。摄取增加的第二个时期与肝细胞DNA合成的增加相吻合。在部分肝切除时给予秋水仙碱和其他微管破坏剂，消除了氨基酸摄取增加的第一个时期，并阻止细胞开始DNA合成。用α-氨基异丁酸进行脉冲标记实验表明，秋水仙碱本身并不抑制氨基酸转运，但阻止了部分肝切除诱导的氨基酸转运能力的增加。肝切除后14小时注射秋水仙碱可阻止肝脏释放氨基酸，并大大减少DNA合成的起始。数据表明，微管可能在体内肝细胞的增殖激活以及DNA合成起始中起作用，并且氨基酸转运的变化与这些需要微管的过程相关。
