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ARS Home » Plains Area » Grand Forks, North Dakota » Grand Forks Human Nutrition Research Center » Dietary Prevention of Obesity-related Disease Research » Research » Publications at this Location » Publication #71362
Title: EXPRESSION OF METALLOTHIONEIN IN THE LIVER OF RATS FED COPPER-DEFICIENT AIN-93 DIET

Author
item KANG, Y - U NORTH DAKOTA
item CHEN, YAN - U NORTH DAKOTA
item Saari, Jack

Submitted to: Trace Elements in Man and Animals International Symposium
Publication Type: Proceedings
Publication Acceptance Date: 5/19/1996
Publication Date: N/A
Citation: N/A

Interpretive Summary: Metallothionein is a protein that protects the body against such stressors as toxic effects of heavy metals and damaging effects of free radicals produced by normal metabolic reactions involving oxygen. Excessive intake of copper in the diet can cause, like other metals, increased production of metallothionein to combat the toxic effects of high tissue copper content. The purpose of the present study was to determine the effect of low dietary copper on metallothionein production. In livers of copper- deficient rats we found that the genetic message that tells the liver cells to produce metallothionein is increased, but that the amount of metallothionein produced is not changed. This indicates that a stressor produced by copper deficiency induces cells to produce additional metallothionein, but that the genetic message generated to do so is not being properly utilized. The stressor is unknown, but it may be high liver iron concentration or excessive production of oxygen-derived free radicals, both known to occur in copper deficiency. The reason that the liver ignores the genetic message is also unknown, but the molecular defect that prevents metallothionein production represents an additional pathological feature of dietary copper deficiency that further emphasizes the need for adequate intake of dietary copper.

Technical Abstract: Copper has a function in regulation of synthesis of metallothionein (MT) a low molecular weight and cysteine-rich protein. Copper-loading, in particular, has been shown to increase MT mRNA and protein concentrations in the liver and other organs of rodents. To assess whether copper is essential for this protein production, the effect of severe dietary copper deficiency on MT expression was determined in the present study. Weanling rats were fed the AIN-93G diet deficient in copper (0.4 ug/g diet) or containing adequate copper (5.7 ug/diet) for 4 weeks. Mineral analysis revealed that copper concentrations were severely depressed in the liver, heart and kidney of the animals fed the copper deficient diet. Iron concentrations were considerably increased in the copper-deficient liver, but slightly decreased in the heart or kidney. The mRNA content for MT-I was markedly elevated in the copper-deficient liver but not in the heart or kidney. The MT protein concentration, however, was not elevated in either liver or heart, and was decreased in the kidney of copper-deficient rats. The results suggest that iron elevation in copper deficient liver is likely to be responsible for the increased MT-I mRNA production. Copper may not be essential for MT transcription, but may be critical for the translation in the rat liver.