Concentration-dependent differential effects of N-acetyl-L-cysteine on the expression of HSP70 and metallothionein genes induced by cadmium in human amniotic cells

被引:24
作者
Abe, T
Yamamura, K
Gotoh, S
Kashimura, M
Higashi, K
机构
[1] Univ Occupat & Environm Hlth, Sch Med, Dept Biochem, Yahatanishi Ku, Fukuoka 807, Japan
[2] Univ Occupat & Environm Hlth, Sch Med, Dept Obstet & Gynecol, Yahatanishi Ku, Fukuoka 807, Japan
来源
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS | 1998年 / 1380卷 / 01期
关键词
cadmium; HSP70; metallothionein; N-acetyl-L-cysteine; human amniotic cell;
D O I
10.1016/S0304-4165(97)00144-X
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cadmium induces the expression of the 70 kDa heat shock: protein (HSP70) and metallothionein (MT), both of which are considered to be associated with intracellular glutathione (GSH) metabolism in the cellular protection mechanism against cadmium-induced cellular injury. We determined the effects of N-acetyl-L-cysteine (NAG), which increases the intracellular GSH levels, on the induction of HSP70 and MT gene expression in a cultured cell line of human amniotic cells (WISH) exposed to CdCl2,. The mRNA level of MT-II, a major isoform of MT genes, was more prominently increased than that of HSP70 when WISH cells were exposed to 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 mu M CdCl2,. This concentration of NAC also efficiently suppressed the cadmium-induced lethality. On the contrary, pretreatment with 1.5mM NAC 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 peroxidation which was increased by 50 mu M CdCl2,. Furthermore, this low concentration of NAG: also decreased the CdCl2-induced gene expression of HSP32 which represents a general response to oxidative stress. Taken together, NAC seems to have at least two concentration-dependent functions in WISH cells exposed to CdCl2,; the low concentration of NRC can suppress the induction of HSP70 gene expression as well as the increase of lipid peroxidation via an antioxidant pathway, while the high concentration of NAC can suppress the induction of MT-II mRNA as well as cadmium-induced cell death. Our present data suggest that changes in intracellular 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 Elsevier Science B.V.
引用
收藏
页码:123 / 132
页数:10
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