Giroux E, Lachmann P J
J Biol Chem. 1984 Mar 25;259(6):3658-62.
Intubation of rats with alpha-mercapto-beta-(2-furyl)-acrylic acid (MFA) for 5 days at 50 mg/kg caused a 7-fold increase in kidney copper concentration, a 2-fold increase in kidney zinc concentration, and a 20% increase in liver zinc concentration. The proteins which bound the increased metals were purified and identified as metallothioneins by their amino acid compositions. Two isoforms were isolated from each organ. Renal thioneins appeared identical to counterpart hepatic apoproteins, but the former bound Cu and Zn in a 2:1 mole ratio and the latter bound only Zn. Kidney contained over 10 times more metallothionein per g of tissue than did liver. In rats previously administered MFA, injection of cadmium sulfate resulted in rapid displacement of liver metallothionein-bound Zn by Cd under conditions where minimal metallothionein was found in Cd-dosed animals not administered MFA. We conclude that MFA induces metallothionein biosynthesis in kidney and liver of normal rats; this is a novel effect for an organic compound.
以50毫克/千克的剂量用α-巯基-β-(2-呋喃基)丙烯酸(MFA)给大鼠插管5天,导致肾脏铜浓度增加7倍,肾脏锌浓度增加2倍,肝脏锌浓度增加20%。结合增加的金属的蛋白质被纯化,并通过其氨基酸组成鉴定为金属硫蛋白。从每个器官中分离出两种亚型。肾脏硫蛋白似乎与相应的肝脏载脂蛋白相同,但前者以2:1的摩尔比结合铜和锌,而后者仅结合锌。每克组织中,肾脏含有的金属硫蛋白比肝脏多10倍以上。在先前给予MFA的大鼠中,在未给予MFA的镉给药动物中发现最低限度金属硫蛋白的条件下,注射硫酸镉导致肝脏金属硫蛋白结合的锌被镉迅速取代。我们得出结论,MFA诱导正常大鼠肾脏和肝脏中的金属硫蛋白生物合成;这是有机化合物的一种新作用。