Bylander J E, Li S L, Sens M A, Sens D A
Robert C. Byrd Health Sciences Center, Department of Pathology, West Virginia University, Morgantown 26506, USA.
Toxicol Lett. 1995 Apr;76(3):209-17. doi: 10.1016/0378-4274(95)80005-x.
Humans, in contrast to animals, have a complex expression of metallothionein (MT) genes which involves many MT isoforms encoded by a family of genes containing an upper limit of 12 possible functional genes. It is unknown if these human isoforms of MT have distinct functions or if they simply represent a non-essential duplication of gene function. In the present study, MT protein and mRNA for the MT-2A, MT-1A, B, E, F, and G genes was determined for 3 isolates of human proximal tubule (HPT) cells having distinct sensitivities to cadmium. For all 3 HPT isolates, the expression of MT protein and mRNA for the MT-2A, MT-1E, MT-1F and MT-1G isoforms was similar among the isolates and demonstrated no correlation to lethality. However, each isoform mRNA was expressed at different levels when compared to one another. In contrast, the expression of MT-1A mRNA differed in expression and correlated with the differing lethalities displayed by each isolate. The finding of different profiles of mRNA expression provides evidence that the MT isoforms may have unique functions and that mRNA for the MT-1A gene could be a potential marker for heavy metal exposure and/or toxicity.
与动物不同，人类金属硫蛋白（MT）基因的表达较为复杂，涉及由一个包含上限为12个可能功能基因的基因家族编码的多种MT异构体。目前尚不清楚这些人类MT异构体是否具有不同的功能，或者它们是否仅仅代表了基因功能的非必需重复。在本研究中，对3株对镉具有不同敏感性的人类近端小管（HPT）细胞分离株测定了MT-2A、MT-1A、B、E、F和G基因的MT蛋白和mRNA。对于所有3株HPT分离株，MT-2A、MT-1E、MT-1F和MT-1G异构体的MT蛋白和mRNA表达在分离株之间相似，且与致死率无关。然而，相互比较时，每种异构体mRNA的表达水平不同。相比之下，MT-1A mRNA的表达不同，且与各分离株表现出的不同致死率相关。mRNA表达谱不同的发现提供了证据，表明MT异构体可能具有独特功能，且MT-1A基因的mRNA可能是重金属暴露和/或毒性的潜在标志物。
