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暴露于化会诱导除毒酶谷氨S转移酶M2的表观遗传修饰

Yu-Ting Kang^1,2, Wan-Jung Yang^1,3, Hsu Chih Huang^1,4

¹Institute of Medicine, Chung-Shan Medical University, Taichung, Taiwan.

Environmental toxicology

|December 5, 2023

概括

(Ni) 暴露会通过表观遗传变化抑制谷氨S转移酶M2 (GST-M2) 的表达,增加肺癌风险. 抗糖尿病药物梅特福明可以恢复GST-M2水平,为尼克尔诱导的损伤提供潜在的化学预防.

科学领域:

环境毒理学环境毒理学
癌症表观遗传学癌症表观遗传学
分子致癌症的产生.

背景情况:

(Ni) 是已知的人类致癌物,与基因毒性和表观毒性影响有关,增加癌症风险.
暴露通过表观遗传调节影响基因表达,影响诸如表皮-介质细胞过渡等途径.
谷氨S转移酶M2 (GST-M2) 对于细胞防御至关重要,其减少的表达与肺癌的不良预后相关.

研究的目的:

研究影响GST-M2表达的表观遗传机制.
评估甲胺作为一种潜在的化学预防剂,用于对抗尼克尔诱导的GST-M2抑制.

主要方法:

细胞暴露于化 (NiCl2) 和甲.
使用定量PCR和西式涂抹对GST-M2表达的分析.
使用甲基化特异性PCR和双硫酸盐测序评估DNA甲基化.
评估组织素乙化和转录因子结合 (Sp1).

主要成果:

化暴露抑制了GST-M2的表达,通过促进剂高甲基化和改变的基因素乙化.
甲胺和去甲基化剂恢复了GST-M2的表达.
化破坏了Sp1转录因子与GST-M2促进体的结合.
甲胺抵消了对组织素H3表达的抑制作用,并恢复了Sp1结合.

结论:

通过表观遗传修饰减少了GST-M2表达和转录活性,可能导致肺癌发生.
甲胺通过逆转诱导的表观遗传变化并恢复GST-M2表达,显示出化学预防潜力.

关键词:

表观遗传修饰是一种表观遗传修饰.谷氨 S-转移酶 M2 的作用.甲胺是一种甲胺.尼克尔尼克尔是什么意思特异性蛋白质 1 1 的特异性

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