Regulation of Cell Fate by Cadmium and Zinc.

Abstract

Effects of the heavy metals cadmium and zinc on the regulation of cell destiny are reviewed in light of an apoptogenic metal of cadmium and the antiapoptotic nature of zinc. Exposure of renal cells to cadmium causes apoptotic features, DNA fragmentation and chromatin condensation in earlier stages of cadmium cytotoxicity than the cadmium-induced necrotic phase. The molecular mechanism of cadmium-induced apoptosis is poorly understood. Neither cadmium-metallothionein nor an immediate early gene such as c-myc is involved in the apoptotic pathway. In contrast, zinc can abolish cadmium-induced apoptosis. Although the mechanism underlying zinc inhibition of apoptosis remains uncertain, one possibility is that the ability of zinc to facilitate DNA synthesis might contribute to its protective effect on apoptosis.Key words ---apoptosis, cadmium, zinc *To whom correspondence should be addressed: Regional Environment Division, National Institute for Environmental Studies, Tsukuba 305-0053, Japan. Tel.: +81-298-50-2396; Fax: +81-298-50-2571; E-mail: ishidou@nies.go.jp Cadmium is a nephrotoxic metal.1) The proximal tubule of the mammalian kidney is a major target of chronic cadmium-induced toxicity.2) Cadmium chloride induces the synthesis of metallothionein in the liver, which, when released into circulation, is taken up by renal tubule cells.3) In the kidney, cadmium associated with metallothionein is degraded in lysosomal compartments, and the released cadmium in turn stimulates a cascade of toxic effects. 4)The development of cadmium-induced lesions in the kidney is characterized by proteinuria and excessive urinary excretion of other substrates such as enzymes, amino acids, and glucose.

Epitope-Tagged Metallothionein: Its Biochemical and Immunocytochemical Applications.

“…Recent discovery of the apoptogenic nature of cadmium has revealed that metallothionein would be involved in a necrotic phase for the metal detoxification, 16,[19][20][21][22][23] whereas a putative oncogene such as Bcl-2 but not c-MYC largely attenuated cadmium toxicity in an apoptotic phase. 16,24) For further toxicological study of metallothionein using the Flagmetallothionein, a stable clone must be established since the population of the expressed fusion proteins is low in a transient expression system (Fig.…”

Cytotoxicity of Heavy Metals to A Thyroid Carcinoma Cell Line

“…Many of the mechanisms of pollutant action are still incompletely understood. Multiple heavy metals can cause renal insufficiency and necrosis [1,2]. Although such illnesses are considered to be related to the action of proteins such as a metallothionein and to depend on the form of metal involved [2][3][4], details on the toxic mechanism are still lacking.…”

HSP70-Ran-RCC1 transport system during cadmium-induced apoptosis in porcine kidney LLC-PK₁ cells

“…Exposure of cells to cadmium evokes a number of responses that involve not only death-signaling reactions, but also reactions that protect the cells against toxicity (Ishido and Kunimoto, 2001). Accordingly, it has proven difficult to identify the pathways activated by the metal during cell death.…”