A comparison of isometallothionein synthesis in rat liver after partial hepatectomy and parenteral zinc injection

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Abstract
The time course of hepatic Zn-isometallothionein synthesis was studied in the regenerating liver and compared with that produced after the parenteral injection of Zn (6 mg of Zn2+/kg). In the regenerating liver Zn levels rose rapidly after partial hepatectomy and reached a maximum at .apprx. 14 h before declining to approximately normal levels at 48 h postoperation. During this 48 h period most of the Zn 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 Zn between the 2 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 as more MT2 than MT1. In contrast, the i.p. injection of Zn produced a biphasic uptake of Zn into the liver with maxima at 10h and 32h. During the 1st phase of Zn 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 26.18 h and 16.44 h, respectively, in the regenerating liver and 14.75 h and 9.3 h after Zn injection. Thus, thionein disappearance/degradatin in the regenerating liver was slower than that seen after Zn 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 Zn injection, where both isometallothioneins were synthesized in equal amounts. The rates of synthesis of MT2 and MT1 can apparently be altered according to the metabolic status of the cell. A specific role for MT2 during liver regeneration is suggested.