Kershaw W C, Klaassen C D
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City 66103.
Toxicol Appl Pharmacol. 1992 Jan;112(1):24-31. doi: 10.1016/0041-008x(92)90275-w.
Recently, our laboratory demonstrated that metallothionein-1 (MT-1) is degraded faster than metallothionein-2 (MT-2) in liver of Zn-treated adult rats; however, it is not clear whether this phenomenon is unique to Zn treatment or the age of the animal. Furthermore, many investigators maintain that the degradation of MT is regulated by its metal composition. The objective of this study was twofold: (1) to determine if MT-1 is more susceptible than MT-2 to proteolytic breakdown regardless of age or chemical pretreatment and (2) to examine the hypothesis that the amount and type of metals bound to MT influences its resistance to degradation. Pulse-labeling experiments were conducted to determine the half-lives of MT-1 and MT-2 in liver of adult rats (75-day-old), immature rats (1-day-old), and mature rats treated with single dosages of Zn (1 mmol/kg, sc), Cd (10 mumol/kg, sc), or ethanol (109 mmol/kg, po). Atomic absorption spectrometry was utilized to measure the Zn, Cu, and Cd contents of MT-1 and MT-2 obtained in selected experimental groups. MT-1 had a shorter half-life than MT-2 in Zn-treated adults (21 vs 33 hr) and in nontreated immature rats (49 vs 73 hr). In contrast, the half-life values of MT-1 and MT-2 were identical in nontreated adults (4 hr) and ethanol-treated adults (9 hr) and nearly identical in Cd-treated adults (58 and 61 hr, respectively). Both isoforms obtained from immature rats and adults treated with Zn or ethanol contained approximately 6.0 g atoms Zn/mol MT, trace levels of Cu, and nondetectable quantities of Cd. In Cd-treated rats, both isoforms contained approximately equal amounts of Zn and Cd (3.2 g atoms metal/mol MT) and trace levels of Cu. These results indicate that MT-1 is either as susceptible or more susceptible than MT-2 to intracellular degradation depending on age or chemical pretreatment. Furthermore, factors unrelated to the metal composition of MT appear to regulate the degradation of MT-1 and MT-2.
最近，我们实验室证明，在经锌处理的成年大鼠肝脏中，金属硫蛋白-1（MT-1）的降解速度比金属硫蛋白-2（MT-2）更快；然而，尚不清楚这种现象是锌处理所特有的，还是与动物年龄有关。此外，许多研究人员认为，MT的降解受其金属组成的调节。本研究的目的有两个：（1）确定无论年龄或化学预处理如何，MT-1是否比MT-2更容易受到蛋白水解破坏；（2）检验与MT结合的金属的数量和类型影响其抗降解能力这一假设。进行脉冲标记实验以确定成年大鼠（75日龄）、未成熟大鼠（1日龄）以及经单次剂量锌（1 mmol/kg，皮下注射）、镉（10 μmol/kg，皮下注射）或乙醇（109 mmol/kg，口服）处理的成熟大鼠肝脏中MT-1和MT-2的半衰期。利用原子吸收光谱法测量选定实验组中获得的MT-1和MT-2的锌、铜和镉含量。在经锌处理的成年大鼠（21小时对33小时）和未处理的未成熟大鼠（49小时对73小时）中，MT-1的半衰期比MT-2短。相比之下，在未处理的成年大鼠（4小时）和经乙醇处理的成年大鼠（9小时）中，MT-1和MT-2的半衰期值相同，在经镉处理的成年大鼠中（分别为58小时和61小时）几乎相同。从未成熟大鼠以及经锌或乙醇处理的成年大鼠中获得的两种亚型均含有约6.0克原子锌/摩尔MT、微量铜以及无法检测到的镉含量。在经镉处理的大鼠中，两种亚型所含的锌和镉量大致相等（3.2克原子金属/摩尔MT）以及微量铜。这些结果表明，根据年龄或化学预处理情况，MT-1对细胞内降解的敏感性与MT-2相当或更高。此外，与MT金属组成无关的因素似乎调节着MT-1和MT-2的降解。
