通过调节HDAC2,Pb抑制了C2C12髓母细胞的分化
Xiaozhen Gu1, Nan Shen1, Chengqing Huang1
1Engineering Research Center of Bio-process, Ministry of Education, Hefei University of Technology, 193 Tunxi Road, Hefei, Anhui 230009, PR China; School of Food and Biological Engineering, Hefei University of Technology, No. 193 of Tunxi Road, Baohe District, 230009 Hefei, China.
Toxicology
|October 5, 2023
概括
暴露会通过抑制C2C12神经细胞分化来损害骨肌肉的发育. 这一过程由表观遗传调节剂素脱乙酶-2 (HDAC2) 介导,突出了一个新的毒性途径.
科学领域:
- 细胞生物学 细胞生物学
- 毒理学 毒理学 毒理学
- 发展生物学 发展生物学
背景情况:
- 肌肉发育对于骨肌肉发育和恒常状态至关重要.
- (Pb) 暴露会对骨健康产生负面影响,特别是在儿童中.
- 对骨肌肉发育的具体影响仍然在很大程度上是未知的.
研究的目的:
- 研究 (Pb) 对C2C12核细胞增殖和分化的有毒作用.
- 为了阐明基因素脱乙酶-2 (HDAC2) 在Pb诱导的肌肉生成抑制中的作用.
主要方法:
- C2C12神经质被暴露于不同度的Pb (1,5,10微米).
- 进行了细胞活力测试以评估Pb的毒性.
- 分析了肌源性差异化标志物 (MCK,MYH4,MYOG,MYOD) 和HDAC2表达.
- 使用HDAC2敲击来确定它在Pb诱导的差异化缺陷中的作用.
主要成果:
- 在5微米和10微米的Pb暴露显著降低了C2C12细胞活力.
- 暴露于Pb (1-10μM) 显著抑制了肌细胞分化,减少了关键的肌原标记基因表达.
- 暴露于导致C2C12核细胞中组织脱乙酶-2 (HDAC2) 的上调.
- 击败HDAC2部分挽救了Pb诱导的C2C12髓细胞分化的抑制.
结论:
- 暴露于会通过损害C2C12神经细胞分化来抑制骨肌肉的发育.
- 表观遗传修饰剂基因组脱乙酸酶-2 (HDAC2) 在调解Pb诱导的神经发生缺陷方面发挥着关键作用.
- 这些发现揭示了毒性影响骨肌肉发育的新型机制.
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