Acute cadmium exposure induces stress-related gene expression in wild-type and metallothionein-I/II-null mice
Acute cadmium exposure induces stress-related gene expression in wild-type and metallothionein-I/II-null mice
复制标题
DOI：
10.1016/s0891-5849(01)00826-7
复制
发表时间：
2002-03-15
影响因子：
7.4
通讯作者：
Klaassen, CD
中科院分区：
文献类型：
--
作者：
Liu, J;Kadiiska, MB;Klaassen, CD
本研究探讨了急性镉对野生型和金属硫蛋白-I/II-null（MT-null）小鼠应激相关基因表达和自由基产生的影响。Atlas毒理学阵列表明，急性镉（40 μ mol/kg CdCl 2，ip 3 h）显着增加编码热休克蛋白，血红素加氧酶-1，和基因的基因在响应DNA损伤/修复的基因的表达。编码细胞色素P450酶，UDP-葡萄糖醛酸转移酶，锰-超氧化物歧化酶和过氧化氢酶的基因的表达被镉抑制。MT基因敲除小鼠比野生型小鼠对镉诱导的应激相关基因表达更敏感，这与转录因子AP-1和磷酸化JNK和ERK的更大激活雅阁。为了评估自由基的产生，小鼠同时给予自旋捕获剂N-叔丁基-α-苯基硝酮（PBN，250 mg DMSO/kg，ip）和镉，30 min后取出肝脏，用氯仿：甲醇（2：1）进行PBN捕获的自由基提取，并用电子自旋共振（ESR）检测。镉治疗引起可检测的ESR信号PBN加合物，以及在肝脏中的脂质过氧化反应类似的野生型和MT-null小鼠。因此，急性镉毒性的机制涉及多个方面，包括氧化损伤和基因表达异常，和NIT的缺乏加剧镉诱导的基因表达异常。(C)2002年爱思唯尔科技有限公司
This study examined the effect of acute cadmium on stress-related gene expression and free radical production in wild-type and metallothionein-I/II-null (MT-null) mice. Atlas Toxicology arrays showed that acute cadmium (40 mumol/kg as CdCl2, ip for 3 h) markedly increased the expression of genes encoding heat-shock proteins, heme oxygenase-1, and genes in response to DNA damage/repair. The expression of genes encoding cytochrome P450 enzymes, UDP-glucuronosyltransferases, Mn-superoxide dismutase, and catalase was suppressed by cadmium. MT-null mice were more sensitive than wild-type mice to cadmium-induced, stress-related gene expression, in accord with greater activation of transcription factor AP-1 and phosphorylated JNK and ERK. To evaluate free radical production, mice were simultaneously given the spin trap agent, N-tert-butyl-alpha-phenylnitrone (PBN, 250 mg in DMSO/kg, ip) with cadmium, and livers were removed 30 min later for PBN-trapped radical extraction with chloroform: methanol (2: 1), and detected with electron spin resonance (ESR). Cadmium treatment caused detectable ESR signals for PBN adducts as well as lipid peroxidation in the liver similarly in both wild-type and MT-null mice. Thus, the mechanism of acute cadmium toxicity involves multiple facets including oxidative damage and aberrant gene expression, and absence of NIT exacerbates Cd-induced aberrant gene expression. (C) 2002 Elsevier Science Inc.