Cain K, Griffiths B L
Biochem J. 1984 Jan 1;217(1):85-92. doi: 10.1042/bj2170085.
The time course of hepatic zinc-isometallothionein synthesis was studied in the regenerating liver and compared with that produced after the parenteral injection of zinc (6 mg of Zn2+/kg). In the regenerating liver, zinc levels rose rapidly after partial hepatectomy and reached a maximum at approx. 14h before declining to approximately normal levels at 48h post-operation. During this 48h period most of the zinc was incorporated into metallothionein. Purification of the latter into the charge-separable isometallothioneins (i.e. MT1 and MT2) showed that, in the regenerating liver, there was an unequal distribution of zinc between the two isoproteins. Thus at operation the endogenous thionein had an MT2/MT1 ratio of 1; after regeneration this ratio increased, and all times during the time course there was more MT2 than MT1. In contrast, the intraperitoneal injection of zinc produced a biphasic uptake of zinc into the liver with maxima at 10h and 32h. During the first phase of zinc uptake, metallothionein synthesis increased rapidly and, unlike the regenerating liver, the MT2/MT1 ratio of 1 remained constant. Thereafter, this ratio increased in a manner analogous to that exhibited by the regenerating liver. Half-life determinations for thionein disappearance/degradation shows that MT2 and MT1 were degraded with half-lives (t1/2) of 26.18h and 16.44h respectively in the regenerating liver and 14.75h and 9.3h after zinc injection. Thus thionein disappearance/degradation in the regenerating liver was slower than that seen after zinc injection. However, in both situations MT2 was always removed at a slower rate than MT1. Calculation of the rates of thionein synthesis (assuming the above disappearance rates were constant throughout the time course) showed that, in the regenerating liver, the rate of MT2 synthesis was approximately twice that of MT1. This was not the case after zinc injection, where both isometallothioneins were synthesized in equal amounts. These results demonstrate that the rates of synthesis of MT2 and MT1 can be altered according to the metabolic status of the cell and suggest a specific role for MT2 during liver regeneration.
在再生肝中研究了肝锌 - 异金属硫蛋白合成的时间进程，并与经肠胃外注射锌（6mg Zn²⁺/kg）后产生的情况进行了比较。在再生肝中，部分肝切除术后锌水平迅速升高，约在14小时达到最高值，然后在术后48小时降至大致正常水平。在这48小时期间，大部分锌被整合到金属硫蛋白中。将后者纯化成分离电荷的异金属硫蛋白（即MT1和MT2）表明，在再生肝中，两种同工蛋白之间锌的分布不均。因此，在手术时内源性硫蛋白的MT2/MT1比值为1；再生后该比值增加，并且在整个时间进程中的所有时间MT2都比MT1多。相比之下，腹腔注射锌导致锌向肝脏的摄取呈双相性，在10小时和32小时达到最大值。在锌摄取的第一阶段，金属硫蛋白合成迅速增加，与再生肝不同，MT2/MT1比值保持恒定为1。此后，该比值以类似于再生肝的方式增加。硫蛋白消失/降解的半衰期测定表明，在再生肝中MT2和MT1的降解半衰期（t1/2）分别为26.18小时和16.44小时，注射锌后分别为14.75小时和9.3小时。因此，再生肝中硫蛋白的消失/降解比注射锌后慢。然而，在两种情况下MT2的去除速度总是比MT1慢。硫蛋白合成速率的计算（假设上述消失速率在整个时间进程中恒定）表明，在再生肝中，MT2的合成速率约为MT1的两倍。注射锌后情况并非如此，此时两种异金属硫蛋白的合成量相等。这些结果表明，MT2和MT1的合成速率可根据细胞的代谢状态而改变，并提示MT2在肝脏再生过程中具有特定作用。
