Zalups R K, Koropatnick J
Division of Basic Medical Sciences, Mercer University School of Medicine, Macon, Georgia, USA.
J Pharmacol Exp Ther. 2000 Oct;295(1):74-82.
Metallothioneins are encoded by a family of genes that are induced by inorganic mercury. Despite the well-characterized acute response of metallothionein (MT) genes in the kidneys and liver after a single exposure to inorganic mercury, relatively little is known about the activity of these genes and the content of MT protein during prolonged periods after exposure. Rats treated with inorganic mercury accumulate mercury rapidly in kidneys and liver during the first 24 h after exposure, but only in the kidneys does the content of mercury remain elevated throughout the initial 2 weeks. We report herein that transcription of MT genes in response to treatment with inorganic mercury differs dramatically between the kidneys and liver. MT gene transcription and levels of MT protein remained elevated in the kidneys throughout 14 days after treatment. In contrast, the initially high rates of MT gene transcription and enhanced content of MT protein in the liver fell to control levels by 14 days. In the liver, the rates of MT gene transcription and levels of MT protein were strongly correlated with each other and with the content of mercury. In the kidneys, however, these correlations were very weak or absent. Our data indicate that hepatic levels of MT protein are determined primarily by MT gene transcription, but that post-transcriptional events are important in determining the renal content of MT protein during the initial weeks after exposure. This has important implications in understanding differences in mechanisms controlling MT expression in the kidneys and liver.
金属硫蛋白由一组可被无机汞诱导的基因编码。尽管单次接触无机汞后肾脏和肝脏中金属硫蛋白（MT）基因的急性反应已得到充分表征，但对于这些基因在接触后的较长时期内的活性以及MT蛋白的含量却知之甚少。用无机汞处理的大鼠在接触后的最初24小时内，肾脏和肝脏中迅速积累汞，但仅在肾脏中，汞含量在最初的2周内一直保持升高。我们在此报告，肾脏和肝脏中无机汞处理后MT基因的转录存在显著差异。处理后14天内，肾脏中MT基因的转录和MT蛋白水平一直保持升高。相比之下，肝脏中最初较高的MT基因转录速率和MT蛋白含量增加在14天时降至对照水平。在肝脏中，MT基因的转录速率和MT蛋白水平彼此之间以及与汞含量都密切相关。然而，在肾脏中，这些相关性非常弱或不存在。我们的数据表明，肝脏中MT蛋白水平主要由MT基因转录决定，但转录后事件在接触后的最初几周内对决定肾脏中MT蛋白含量很重要。这对于理解控制肾脏和肝脏中MT表达的机制差异具有重要意义。
