Implication of free radicals and glutathione in the mechanism of cadmium-induced expression of stress proteins in the A549 human lung cell-line

Cellular mechanisms underlying the expression of stress proteins (HSP) were studied in the human cell-line A549 submitted to a pollutant, cadmium, in the presence of several agents which modulate the glutathione level and, su pposedly, the effects of this metal in the cell. It was observed that HSP 9 0, HSP 72 and HSP 27 are significantly over-expressed after exposure to cad mium chloride for 24 h. Low cadmium concentrations (i.e. from 1 to 10 mu M) also triggered a slight accumulation of glutathione, whereas this compound was depleted after exposure to higher cadmium concentrations (25-100 mu M) When 50 CIM diethyl-maleate, which traps glutathione, was added together w ith cadmium, the over-expression of HSP 72 and HSP 90 was much stronger. Tr eatment of cells with 20 or 40 mM N-acetyl-L-cysteine, which traps free rad icals, was found to increase by 30% the glutathione level and to suppress t he HSP over-expression. From our results, it is suggested that HSP inductio n by cadmium in A549 cells is due, at least in part, to the oxidative stres s consisting in formation of reactive oxygen species and inhibition of pero xides detoxification. Due to this oxidative status within the cell, more pr oteins would be damaged inducing the HSP over-expression. (C) 2000 Elsevier Science B.V. All rights reserved.