Metallothionein is an integral component of the mechanism that regulates the metabolism of cadmium and zinc. The synthesis of this protein can be "induced" by oral or parenteral administration of either metal. The metallothionein mRNA content of liver polysomes is increased shortly after an influx of small amounts of either metal into hepatocytes. After sufficient amounts of this poly (A+) RNA ...

Acquired drug resistance is one of the most important problems in cancer chemotherapy. One of the proposed mechanisms for these phenomena is the sequestration of alkylating agents by metallothionein in vivo. This research shows that metallothionein can covalently sequester phosphoramide mustard, the active form of cyclophosphamide in vitro. On-line electrospray mass spectrometry reveals that it...

There is a need to identify specific biological indicator(s) of cadmium exposure so that the renal damage can be prevented. Towards this end, we have examined the usefulness of urinary metallothionein as an indicator of cadmium body burden. It is found that, in both animals and humans, urinary metallothionein level is related to the hepatic and renal cadmium burdens. Significant correlations ar...

Lead is an environmental nephrotoxicant and probable human carcinogen. Elucidating factors predisposing populations to lead toxicity is an important public health issue. Recently, we found that metallothionein-I/-II double knockout (metallothionein-null) mice that are unable to produce the major forms of metallothionein do not produce lead inclusion bodies, which are thought to mitigate lead to...

Icefish (family Channichthyidae, suborder Nothothenioidei) are a group of Antarctic fish that have evolved unique phenotypes in order to adapt to the environment in which they live. Besides the lack of haemoglobin and the drastic reduction in the number of erythrocyte-like cells, another striking feature of the icefish is that their liver is devoid of metallothionein. These cysteine-rich heavy-...

Metallothionein concentrations in erythrocyte lysates derived from human subjects were measured by an ELISA procedure. IgG obtained from serum of sheep injected with human metallothionein 1 was used in this competitive assay. Subjects were fed a semipurified zinc-deficient diet (0.7 mg of zinc per kg of diet) for an 8-day depletion period after 3 days of acclimation. Fasting plasma zinc concent...

Senescence is accompanied by oxidative stress and cardiac dysfunction, although the link between the two remains unclear. This study examined the role of antioxidant metallothionein on cardiomyocyte function, superoxide generation, the oxidative stress biomarker aconitase activity, cytochrome c release, and expression of oxidative stress-related proteins, such as the GTPase RhoA and NADPH oxida...

Our investigation was centered on a possible relationship between the toxicity of cadmium and changes in its chemical forms in tissues. Two models have been studied: one is the renal damage induced by a single injection of cadmium-containing metallothionein and the other is the renal damage induced by repeated injections of cadmium salt. Parenteral loading of cadmium-containing metallothionein ...

Metallothionein is a low molecular weight, cysteine-rich, stress response protein that can act as an antioxidant and as an immunosuppressive agent in instances of antigen-dependent adaptive immunity. In this context, we assessed the therapeutic potential and mechanisms of action of metallothionein in a collagen-induced arthritis model. Repeated administration of metallothionein-I + II during th...

Recent reports have strongly implicated glucocorticoids in the induction of hepatic metallothionein synthesis and hypozincemia which occurs in certain pathophysiologic conditions. Studies were performed in rats to determine the effect of adrenalectomy and glucocorticoid treatment on the hepatic accumulation of metallothionein subsequent to the administration of cadmium and turpentine, two diver...