Expression of stress-related genes in a cadmium-resistant A549 human cell line.
This study was designed to explain the basis for Cd-acquired tolerance of A549 cells cultured in the presence of Cd. Thirty-day exposure of cultured human pneumocytes (A549 cell line) to 10 microM Cd was previously found to induce an acquired resistance persisting over several weeks of culture. Moreover, these Cd-resistant cells (R-cells) were found to proliferate faster than controls. No difference was found between R-cells and control cells (S-cells) concerning the basal and Cd-induced level of metallothioneins expression. However, after exposure to Cd, cell glutathione levels were unchanged in R-cells while they were either increased (at 10 microM Cd) or decreased (at 25 microM Cd) in S-cells. cDNA array analysis showed that genes encoding for (GPx1) glutathione peroxidase, glutathione reductase, catalase, and superoxide dismutase were similarly expressed in R- and S-cells, whereas the gene of (GPx2) glutathione peroxidase was overexpressed in R-cells. Most genes encoding stress proteins were similarly expressed, except for HSP27 and GRP94 genes, which were respectively under- (ratio 0.5 +/- 0.1) and over- (1.8 +/- 0.5) expressed in R-cells. Acute exposure to Cd was found to trigger the upregulation of genes encoding the chaperone proteins HSP90A, HSP27, HSP40, GRP78, HSP72, and HO-1 in S-cells. In R-cells, only HO-1 and HSP72 were overexpressed but at a lower level. This suggests that the Cd-related adverse conditions, leading to protein misfolding, are lowered in R-cells. It is likely that the upregulation of GPx2 in R-cells leads to a higher antioxidant defense in these cells.
Croute
Françoise
F
Laboratoire de Biologie Cellulaire et Pollution, Faculté de Médecine Toulouse-Purpan, Toulouse, France. croute@cict.fr
Beau
Bernadette
B
Murat
Jean-Claude
JC
Vincent
Christian
C
Komatsu
Hiroyoshi
H
Obata
Fumiya
F
Soleilhavoup
Jean-Pierre
JP
D000230:Adenocarcinoma; D002104:Cadmium / Q000633:toxicity*; D000091342:Endoplasmic Reticulum Chaperone BiP; D020869:Gene Expression Profiling; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics*; D014407:Tumor Cells, Cultured
D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D002104:Cadmium; D005978:Glutathione