Southern California Coastal Water Research Project, Costa Mesa, CA 92626, United States; Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611, United States.
Department of Human Genetics, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, United States; Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611, United States.
Aquat Toxicol. 2014 Jul;152:186-94. doi: 10.1016/j.aquatox.2014.04.004. Epub 2014 Apr 15.
Cadmium is a heavy metal that can accumulate to toxic levels in the environment leading to detrimental effects in animals and humans including kidney, liver and lung injuries. Using a transcriptomics approach, genes and cellular pathways affected by a low dose of cadmium were investigated. Adult largemouth bass were intraperitoneally injected with 20μg/kg of cadmium chloride (mean exposure level - 2.6μg of cadmium per fish) and microarray analyses were conducted in the liver and testis 48h after injection. Transcriptomic profiles identified in response to cadmium exposure were tissue-specific with the most differential expression changes found in the liver tissues, which also contained much higher levels of cadmium than the testis. Acute exposure to a low dose of cadmium induced oxidative stress response and oxidative damage pathways in the liver. The mRNA levels of antioxidants such as catalase increased and numerous transcripts related to DNA damage and DNA repair were significantly altered. Hepatic mRNA levels of metallothionein, a molecular marker of metal exposure, did not increase significantly after 48h exposure. Carbohydrate metabolic pathways were also disrupted with hepatic transcripts such as UDP-glucose, pyrophosphorylase 2, and sorbitol dehydrogenase highly induced. Both tissues exhibited a disruption of steroid signaling pathways. In the testis, estrogen receptor beta and transcripts linked to cholesterol metabolism were suppressed. On the contrary, genes involved in cholesterol metabolism were highly increased in the liver including genes encoding for the rate limiting steroidogenic acute regulatory protein and the catalytic enzyme 7-dehydrocholesterol reductase. Integration of the transcriptomic data using functional enrichment analyses revealed a number of enriched gene networks associated with previously reported adverse outcomes of cadmium exposure such as liver toxicity and impaired reproduction.
镉是一种重金属，在环境中会积累到有毒水平，对动物和人类造成肾脏、肝脏和肺部损伤等有害影响。本研究采用转录组学方法，研究了低剂量镉暴露影响的基因和细胞途径。成年大口黑鲈经腹腔注射 20μg/kg 的氯化镉（平均暴露水平为每尾鱼 2.6μg 镉），注射后 48 小时在肝脏和睾丸进行微阵列分析。转录组谱分析确定了对镉暴露的反应具有组织特异性，肝脏组织的差异表达变化最大，其镉含量也明显高于睾丸。急性低剂量镉暴露在肝脏中诱导了氧化应激反应和氧化损伤途径。抗氧化剂如过氧化氢酶的 mRNA 水平增加，许多与 DNA 损伤和 DNA 修复相关的转录本发生了显著改变。金属暴露的分子标志物——肝金属硫蛋白的 mRNA 水平在 48 小时暴露后并未显著增加。碳水化合物代谢途径也被打乱，肝脏转录本如 UDP-葡萄糖、焦磷酸化酶 2 和山梨醇脱氢酶显著诱导。两种组织都表现出类固醇信号通路的破坏。在睾丸中，雌激素受体β和与胆固醇代谢相关的转录本受到抑制。相反，肝脏中与胆固醇代谢相关的基因高度增加，包括编码限速类固醇生成急性调节蛋白和催化酶 7-脱氢胆固醇还原酶的基因。使用功能富集分析整合转录组数据，揭示了与镉暴露的先前报道的不良后果（如肝毒性和生殖功能受损）相关的多个富集基因网络。
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