INCREASE IN METALLOTHIONEIN PRODUCED BY CHEMICALS THAT INDUCE OXIDATIVE STRESS
INCREASE IN METALLOTHIONEIN PRODUCED BY CHEMICALS THAT INDUCE OXIDATIVE STRESS
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DOI：
10.1016/s0041-008x(05)80017-1
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发表时间：
1991-09-01
影响因子：
3.8
通讯作者：
KLAASSEN, CD
中科院分区：
文献类型：
--
作者：
BAUMAN, JW;LIU, J;KLAASSEN, CD
金属硫蛋白（MT）是一种低分子量蛋白质，具有高半胱氨酸含量，被认为在对抗氧化应激方面发挥作用。例如，MT已被证明是体外羟基自由基的清除剂，具有高水平MT的细胞对辐射具有抗性。然而，尚不清楚引起氧化应激的化合物是否会影响MT水平。因此，小鼠皮下注射11种化学品（叔丁基过氧化氢，百草枯，敌草快，甲萘醌，甲硝唑，阿霉素，3-甲基吲哚，顺铂，二酰胺，马来酸二乙酯，和佛尔酮），产生氧化应激的四个主要机制。MT定量的主要器官（肝，胰腺，脾，肾，肠，心脏和肺）的细胞质中的镉/血红蛋白放射性测定24小时后，管理的化学品。所有药物均显著增加至少一个器官中的MT水平。肝脏对这些药物的反应最大，因为所有11种化学物质都增加了肝脏中的MT浓度，马来酸二乙酯、百草枯和二酰胺增加了20至30倍。胰腺和肾脏是对这些化学物质反应最快的器官。对这些药物反应最小的器官是心脏，因为只有3种化合物引起心脏中MT浓度的显著增加。马来酸二乙酯和敌草快是最常见的MT诱导剂，因为它们在检查的7个器官中的6个中增加MT。没有处理导致任何器官中MT浓度的显著降低。总之，通过四种不同机制之一产生氧化应激的化学物质在增加各种器官中的MT浓度方面非常有效。这表明MT可能参与保护免受氧化应激。
Metallothionein (MT) is a low-molecular-weight protein with a high cysteine content that has been proposed to play a role in protecting against oxidative stress. For example, MT has been shown to be a scavenger of hydroxyl radicals in vitro, and cells with high levels of MT are resistant to radiation. However, it is not known if compounds that cause oxidative stress affect MT levels. Therefore, mice were injected subcutaneously with 11 chemicals (t-butyl hydroperoxide, paraquat, diquat, menadione, metronidazole, adriamycin, 3-methylindole, cisplatin, diamide, diethyl maleate, and phorone) that produce oxidative stress by four main mechanisms. MT was quantitated in the cytosol of major organs (liver, pancreas, spleen, kidney, intestine, heart, and lung) by the Cd/hemoglobin radioassay 24 hr after administration of the chemicals. All agents significantly increased MT levels in at least one organ. Liver was the most responsive to these agents in that all 11 chemicals increased MT concentrations in liver, with diethyl maleate, paraquat, and diamide producing 20- to 30-fold increases. Pancreas and kidney were the next most responsive organs to these chemicals. The organ least responsive to these agents was the heart, as only 3 compounds caused significant increases in MT concentrations in heart. Diethyl maleate and diquat were the most general inducers of MT in that they increased MT in six of the seven organs examined. No treatment resulted in a significant decrease in MT concentration in any organ. In conclusion, chemicals that produce oxidative stress by one of four distinct mechanisms are very effective at increasing MT concentrations in a variety of organs. This suggests that MT might be involved in protecting against oxidative stress.