Analysis of cysteine and histidine residues required for zinc response of the transcription factor human MTF-1.

Metal responsive element (MRE)-binding transcription factor-1 (MTF-1) is a zinc finger (ZF) transcription factor that plays a key role in heavy metal homeostasis by regulating relevant genes in response to metals. MTF-1 is known to be activated by heavy metals such as Zn and Cd, but the mechanism of activation remains unclear. In the present study, Cys and His residues of human MTF-1 (hMTF-1), some of which may be involved in interaction with metals or with each other, were screened for their contribution to Zn-dependent transcription.

Cadmium-induced alterations of gene expression in human cells.

We have reported the changes in gene expression in human HeLa cells exposed to a low concentration (5μM) of Cd. In the present study, cells exposed to a higher concentration of Cd were analyzed using a DNA microarray with 9182 human cDNA probes, in an attempt to obtain a comprehensive view on the biological effects of Cd. After a 6h exposure to 50μM Cd, 48 genes were up-regulated 2.

Gene expression profile in human cells exposed to zinc.

Although Zn is an essential trace metal for humans, a comprehensive view of its effects on cellular functions has not been obtained. We used a DNA microarray to assess transcriptional alterations in human HeLa cells after exposure to a moderate concentration of Zn (100 muM ZnSO(4)). Out of 9,182 human genes, expression was increased in 7 genes and decreased in 4 genes twofold or greater.

Ultraviolet irradiation increases the sensitivity of cultured human skin cells to cadmium probably through the inhibition of metallothionein gene expression.

We previously developed an apparatus that can irradiate cultured cells with monochromatic ultraviolet (UV) rays to exactly assess the biological effects of UV components on mammalian cells. Using this device, we studied the effects of UV in and near the UVB region on the general as well as specific protein synthesis of the human skin-derived NB1RGB cells. We found that Cd-induced synthesis of metallothioneins (MTs), which are the proteins involved in the protection against heavy metals and oxidative stress, is inhibited by UV at 280 nm more extensively than total protein synthesis.

DNA microarray analysis of altered gene expression in cadmium-exposed human cells.

Cadmium (Cd) is a heavy metal known to be toxic and carcinogenic, but its mechanism of action remains to be elucidated. Development of the DNA microarray technology has recently made the comprehensive analysis of gene expression possible, and it could be a powerful tool also in toxicological studies. With microarray slides containing 7,000-9,000 genes, we have been studying the gene expression profiles of a human cell line exposed to Cd.

Effect of ultraviolet irradiation on the protein synthesis of human skin cells: a study with a monochromatic ultraviolet irradiation apparatus.

Human beings always suffer from serious risk of exposure to ultraviolet (UV) rays in general as well as in work environments but the health effects of UV are not yet fully understood. To enable fine analysis of the biological effects of UV at any given wavelength, we developed an apparatus that can experimentally irradiate cultured mammalian cells with monochromatic UV rays at any given wavelength. With this device, the effects of UV at 260, 280, 300 and 320 nm on the total protein synthesis of human skin-derived NB1RGB cells were examined.

DNA microarray analysis of human gene expression induced by a non-lethal dose of cadmium.

Cadmium (Cd) is a hazardous heavy metal present in working and living environments. Cd affects many cellular functions, but little is known about the mechanisms of its toxicity and cellular defense against it. Recently, advanced gene expression analysis employing DNA microarrays provided us the means to profile the expression of thousands of genes simultaneously.