Koropatnick J, Cherian M G
Department of Oncology, University of Western Ontario, London, Canada.
J Biochem Toxicol. 1988 Fall;3:159-72. doi: 10.1002/jbt.2570030304.
Cadmium (Cd) exposure in mice induces transcription of metallothionein (MT) mRNA and protein accumulation in both liver and kidney. Resistance to hepatotoxicity through chronic exposure to heavy metals is the result of this induction. However, the same chronic exposure results in damage to kidney. We report here that acute exposure of mice to Cd as cadmium sulfate (CdSO4), which resulted in preferential accumulation of metal in liver, or Cd-metallothionein (CdMT), which resulted in preferential metal accumulation in kidney, induced MT mRNA accumulation in both liver and kidney. However, MT mRNA accumulated to a level twofold higher in liver than in kidney in response to CdSO4. Equivalent doses of CdMT induced MT mRNA accumulation to an equal degree in kidney and liver. While MT mRNA accumulation in kidney was directly proportional to the amount of cadmium in the organ, this was not the case in liver. There, liver MT mRNA was elevated in the absence of elevated tissue cadmium levels. Interestingly, CdMT induced alphafetal protein (AFP) mRNA accumulation in kidney, but not liver. It appears that (a) maximal MT mRNA accumulation in kidney is less than in liver, and (b) liver is capable of accumulating MT mRNA in response to even very low cadmium exposure that may not result in elevated tissue cadmium.
小鼠接触镉(Cd)会诱导金属硫蛋白(MT)mRNA转录以及肝脏和肾脏中蛋白质的积累。通过长期接触重金属产生的对肝毒性的抗性就是这种诱导作用的结果。然而,同样的长期接触会导致肾脏受损。我们在此报告,小鼠急性接触硫酸镉(CdSO4)形式的镉,会使金属优先在肝脏中积累;而接触镉 - 金属硫蛋白(CdMT),则会使金属优先在肾脏中积累,这两种情况都会诱导肝脏和肾脏中MT mRNA的积累。然而,在接触CdSO4后,肝脏中MT mRNA积累的水平比肾脏中高两倍。等量的CdMT在肾脏和肝脏中诱导MT mRNA积累的程度相同。虽然肾脏中MT mRNA的积累与器官中镉的含量成正比,但在肝脏中并非如此。在肝脏中,即使组织镉水平未升高,肝脏MT mRNA也会升高。有趣的是,CdMT会诱导肾脏中α - 胎蛋白(AFP)mRNA的积累,但不会诱导肝脏中AFP mRNA的积累。似乎(a)肾脏中MT mRNA的最大积累量小于肝脏,并且(b)肝脏能够对即使可能不会导致组织镉水平升高的极低镉暴露做出反应,积累MT mRNA。