Methylmercury tolerance is associated with the humoral stress factor gene Turandot A.
Methylmercury tolerance is associated with the humoral stress factor gene Turandot A.
复制标题
DOI：
10.1016/j.ntt.2012.04.007
复制
发表时间：
2012-07
影响因子：
2.9
通讯作者：
Rand, Matthew D.
中科院分区：
文献类型：
--
作者：
Mahapatra, Cecon T.;Rand, Matthew D.
甲基汞（MeHg）是一种针对发育中的神经系统的环境神经毒物。为了了解甲基汞毒性的机制，我们使用果蝇模型确定了赋予甲基汞耐受性的候选基因。对MeHg耐受和不耐受果蝇发育中的幼虫大脑进行全基因组转录分析，发现Turandot A （TotA）是一种潜在的MeHg耐受基因。TotA是果蝇分泌的体液应激反应因子，是保守的先天免疫信号通路的直接靶点。在这里，我们描述了TotA在新产生的等基因系（等值线）中的表达，这些系来自于我们之前建立的mehg耐受和不耐受种群。TotA mRNA转录量和蛋白表达量在耐受性同品系中高于非耐受性同品系。在耐MeHg品系中，TotA表达的升高跨越了幼虫的所有发育阶段，这表明TotA基因在耐MeHg品系和不耐MeHg品系之间的调控存在差异。我们发现，相对于大脑和肠道组织，TotA在耐受果蝇的脂肪体（肝脏等量）中表达最高，并且在脂肪体中选择性上调。脂肪体特异性TotA转基因表达可引起甲基汞耐受性，这在食用甲基汞食物饲养的果蝇的发育中得到了增强。此外，基于细胞的实验表明，高TotA表达的C6细胞比低TotA表达的S2细胞对MeHg的耐受性更强。C6细胞中TotA的下调有降低甲基汞耐受性的趋势。TotA作为MeHg耐受基因的鉴定表明，保守的细胞因子/免疫信号通路在调节MeHg毒性中起作用。
Methylmercury (MeHg) is an environmental neurotoxicant that targets the developing nervous system. In an effort to understand mechanisms of MeHg toxicity we have identified candidate genes that confer tolerance to MeHg using a Drosophila model. Whole genome transcript profiling of developing larval brains of MeHg-tolerant and non-tolerant flies has identified Turandot A (TotA) as a potential MeHg tolerance gene. TotA is a secreted humoral stress response factor in Drosophila that is a direct target of conserved innate immunity signaling pathways. Here we characterize TotA expression in newly generated isogenic lines (isolines) of flies derived from our previously established MeHg-tolerant and non-tolerant populations. TotA mRNA transcript and protein expression is seen to be higher in the tolerant isolines than the non-tolerant lines. Elevated TotA expression in the tolerant lines was seen to span all the larval developmental stages pointing toward a difference in the TotA gene regulation between the MeHg tolerant and non-tolerant strains. We show that TotA is most highly expressed in the fat body (liver equivalent) and is selectively upregulated in the fat body of tolerant flies relative to brain and gut tissues. Fat body-specific transgenic expression of TotA invokes MeHg tolerance as seen by enhanced development of flies reared on MeHg food. In addition, cell based assays show that high TotA expressing C6 cells are more tolerant to MeHg than the low TotA expressing S2 cells. Knockdown of TotA in the C6 cells trends toward a reduction in MeHg tolerance. Identification of TotA as a MeHg tolerance gene suggests a role for conserved cytokine/immune signaling pathways in modulating MeHg toxicity.
登录
查看更多内容
影响因子：
2.9
作者：
Rand, Matthew D.
通讯作者：
Rand, Matthew D.
DOI：
10.1006/bbrc.2001.5067
发表时间：
2001-06-22
影响因子：
3.1
作者：
Ekengren, S;Hultmark, D
通讯作者：
Hultmark, D
DOI：
10.1073/pnas.110149597
发表时间：
2000-06-06
影响因子：
11.1
作者：
Clemens, JC;Worby, CA;Dixon, JE
通讯作者：
Dixon, JE
影响因子：
2.1
作者：
Brun, S;Vidal, S;Lemaitre, B
通讯作者：
Lemaitre, B
影响因子：
3.8
作者：
Mahapatra, Cecon T.;Bond, Jeffrey;Rand, Matthew D.
通讯作者：
Rand, Matthew D.