CONCENTRATION-DEPENDENT DIFFERENTIAL-EFFECTS OF N-ACETYL-L-CYSTEINE ON THE EXPRESSION OF HSP70 AND METALLOTHIONEIN GENES INDUCED BY CADMIUMIN HUMAN AMNIOTIC CELLS
T. Abe et al., CONCENTRATION-DEPENDENT DIFFERENTIAL-EFFECTS OF N-ACETYL-L-CYSTEINE ON THE EXPRESSION OF HSP70 AND METALLOTHIONEIN GENES INDUCED BY CADMIUMIN HUMAN AMNIOTIC CELLS, Biochimica et biophysica acta (G). General subjects, 1380(1), 1998, pp. 123-132
Cadmium induces the expression of the 70 kDa heat shock: protein (HSP7
0) and metallothionein (MT), both of which are considered to be associ
ated with intracellular glutathione (GSH) metabolism in the cellular p
rotection mechanism against cadmium-induced cellular injury. We determ
ined the effects of N-acetyl-L-cysteine (NAG), which increases the int
racellular GSH levels, on the induction of HSP70 and MT gene expressio
n in a cultured cell line of human amniotic cells (WISH) exposed to Cd
Cl2,. The mRNA level of MT-II, a major isoform of MT genes, was more p
rominently increased than that of HSP70 when WISH cells were exposed t
o CdCl2 (5-15 mu M, for 6h). The treatment of WISH cells with 1.5 and
30mM NAC for 2h increased the intracellular GSH levels by 1.4- and 3.1
-fold, respectively. Pretreatment of cells with 30mM NAC significantly
reduced both HSP70 and MT-II mRNA levels in the cells exposed to 50 m
u M CdCl2,. This concentration of NAC also efficiently suppressed the
cadmium-induced lethality. On the contrary, pretreatment with 1.5mM NA
C suppressed only the induction of HSP70 gene expression in the 50 mu
M CdCl2-treated cells, and did not inhibit the metal toxicity. However
, this low concentration of NAC efficiently suppressed lipid peroxidat
ion which was increased by 50 mu M CdCl2,. Furthermore, this low conce
ntration of NAG: also decreased the CdCl2-induced gene expression of H
SP32 which represents a general response to oxidative stress. Taken to
gether, NAC seems to have at least two concentration-dependent functio
ns in WISH cells exposed to CdCl2,; the low concentration of NRC can s
uppress the induction of HSP70 gene expression as well as the increase
of lipid peroxidation via an antioxidant pathway, while the high conc
entration of NAC can suppress the induction of MT-II mRNA as well as c
admium-induced cell death. Our present data suggest that changes in in
tracellular redox status, as reflected by GSH concentration, have more
important effects on the induction of HSP70 mRNA rather than that of
MT-II mRNA in human amniotic cells exposed to cadmium. (C) 1998 Elsevi
er Science B.V.