Lee M J, Saijoh K, Nestler E J, Duman R S, Sumino K
Department of Public Health, Kobe University School of Medicine, Japan.
Arch Toxicol. 1995;69(9):590-5. doi: 10.1007/s002040050218.
Osteonectin gene expression in relation to metallothionein mRNA expression was investigated in various tissues from Cd-treated rats. After a single 50 micromol/kg subcutaneous injection of CdCl2, Cd predominantly accumulated in the liver and metallothionein gene expression significantly increased concomitantly with Cd accumulation, but no alteration of osteonectin gene expression was observed. In the kidney and lung, both metallothionein and osteonectin mRNA increased significantly but the elevation of metallothionein mRNA levels (1 h after Cd administration) preceded that of osteonectin (3 h after administration). A significant elevation of osteonectin mRNA levels was also observed in the testis after 3 h, but that of metallothionein mRNA occurred after 6 h. Not only accumulation of Cd but also increments in both osteonectin and metallothionein mRNA were minimal in the brain, but a significant increase in gene expression was observed after 1 h for osteonectin and after 3 h for metallothionein. Since, except in the testis, metallothionein gene expression preceded osteonectin gene expression, the induced metallothionein might transpose Cd and thereby affect its levels immediately, thus reducing the levels of Cd available for accumulation in other tissues. Hence, the osteonectin-Cd interaction might be secondary to the metallothionein-Cd interaction. However, the fact that osteonectin mRNA was predominantly induced by Cd administration in the target tissues of Cd toxicity, such as the lung, kidney and testis, suggests the possible involvement of osteonectin in Cd intoxication/detoxication mechanisms.
研究了镉处理大鼠不同组织中骨连接蛋白基因表达与金属硫蛋白mRNA表达的关系。单次皮下注射50微摩尔/千克氯化镉后,镉主要蓄积在肝脏,金属硫蛋白基因表达随镉蓄积显著增加,但未观察到骨连接蛋白基因表达的改变。在肾脏和肺中,金属硫蛋白和骨连接蛋白mRNA均显著增加,但金属硫蛋白mRNA水平的升高(镉给药后1小时)先于骨连接蛋白(给药后3小时)。给药3小时后,睾丸中骨连接蛋白mRNA水平也显著升高,但金属硫蛋白mRNA在6小时后升高。镉的蓄积以及骨连接蛋白和金属硫蛋白mRNA的增加在脑中均最小,但骨连接蛋白基因表达在1小时后显著增加,金属硫蛋白在3小时后显著增加。由于除睾丸外,金属硫蛋白基因表达先于骨连接蛋白基因表达,诱导的金属硫蛋白可能转运镉,从而立即影响其水平,从而减少可在其他组织中蓄积的镉水平。因此,骨连接蛋白与镉的相互作用可能继发于金属硫蛋白与镉的相互作用。然而,在镉毒性的靶组织如肺、肾和睾丸中,骨连接蛋白mRNA主要由镉给药诱导,这一事实表明骨连接蛋白可能参与镉中毒/解毒机制。