A review of the evidence that ochratoxin A is an Nrf2 inhibitor: implications for nephrotoxicity and renal carcinogenicity.
A review of the evidence that ochratoxin A is an Nrf2 inhibitor: implications for nephrotoxicity and renal carcinogenicity.
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DOI：
10.3390/toxins6010371
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发表时间：
2014-01-20
期刊：
影响因子：
4.2
通讯作者：
Jennings P
中科院分区：
文献类型：
--
作者：
Limonciel A;Jennings P
几项研究表明，赭曲霉毒素A（OTA）抑制核因子，红细胞2样2（Nrf 2）氧化应激反应途径。在细胞水平，这将减弱（i）谷胱甘肽合成;（ii）氧化谷胱甘肽的再循环;（iii）氧化还原酶的活性;和（iv）II期代谢诱导。这些效应的结合将使细胞和组织更容易受到氧化应激的影响。事实上，Nrf 2敲除动物表现出对各种类型的化学诱导损伤的易感性增加。几项研究表明，OTA暴露可以抑制Nrf 2反应。这种作用最初会导致对生理和化学诱导的细胞应激的敏感性增加。然而，长期暴露于OTA也可能作为Nrf 2或其抑制剂Keap-1的体细胞突变的选择性压力，导致组成性Nrf 2激活。nrf 2过表达赋予生存优势，并且通常与癌细胞存活相关。在这里，我们审查的证据OTA的作用作为Nrf 2抑制剂，并讨论这种机制的影响，肾毒性和致癌性。
Several studies have demonstrated that ochratoxin A (OTA) inhibits the nuclear factor, erythroid 2-like 2 (Nrf2) oxidative stress response pathway. At the cellular level this would attenuate (i) glutathione synthesis; (ii) recycling of oxidised glutathione; (iii) activity of oxidoreductases; and (iv) phase II metabolism inducibility. The effects combined would render the cell and tissue more vulnerable to oxidative stress. Indeed, Nrf2 knock out animals exhibit increased susceptibility to various types of chemical-induced injury. Several studies have shown that OTA exposure can inhibit Nrf2 responses. Such an action would initially lead to increased susceptibility to both physiological and chemical-induced cell stress. However, chronic exposure to OTA may also act as a selective pressure for somatic mutations in Nrf2 or its inhibitor Keap-1, leading to constitutive Nrf2 activation. Nrf2 overexpression confers a survival advantage and is often associated with cancer cell survival. Here we review the evidence for OTA’s role as an Nrf2 inhibitor and discuss the implications of this mechanism in nephrotoxicity and carcinogenicity.
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DOI：
10.1111/j.1439-0396.2008.00838.x
发表时间：
2009-10-01
影响因子：
2.7
作者：
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通讯作者：
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影响因子：
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影响因子：
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作者：
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影响因子：
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