乳酸作为主要的表观遗传碳来源通过核LDH代谢通过基因组素乙化
Yong Jin An1, Sihyang Jo1, Jin-Mo Kim1
1Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul, 08826, Korea.
Experimental & molecular medicine
|October 1, 2023
概括
乳酸盐是一种代谢副产品,通过提供碳单元来推动基因素乙化. 这一过程依赖于核乳酸脱酶 (LDHA),影响基因调节,在胰腺癌中具有重要意义.
科学领域:
- 生物化学 生物化学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 代谢途径 代谢途径
背景情况:
- 对于基因调节至关重要的基因乙化,通常使用低度代谢物.
- 高度代谢副产品在基因素乙化中的作用仍未得到充分研究.
研究的目的:
- 为了研究乳酸盐作为基因素乙化碳源.
- 阐明核乳酸脱酶 (LDHA) 在这个过程中的作用.
- 探索乳酸代谢在表观遗传学和疾病中的相关性.
主要方法:
- 在细胞和纯化的核系统中利用了13C3-乳酸盐追踪.
- 采用乳酸脱酶A (LDHA) 淘汰 (KO) 和异质表达模型.
- 在正常和胰腺癌组织中评估了基因组乙化水平和LDHA核定位.
主要成果:
- 乳酸碳通过氧化依赖的新陈代谢在显著程度上被纳入组素H4 (~60%) 中.
- 核LDHA对于乳酸被纳入组 histones 是必不可少的;它的KO取消了这个过程.
- 乳酸盐增加了基因组乙化,而LDHA抑制降低了它;核LDHA在胰腺癌中升高.
结论:
- 乳酸盐作为主要的碳来源,用于核LDHA的介导下,通过核LDHA的介导下,进行基因组乙化.
- 这突显了细胞代谢和表观遗传调节之间的直接联系.
- 核LDHA在代谢-表观遗传轴中的作用对理解癌症生物学有意义.
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