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4-Hydroxynonenal通过Dicer的翻译后修饰破坏了心力衰竭中的miRNA成熟

Ligia A Kiyuna¹, Darlan S Candido², Luiz R G Bechara¹

¹Department of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof. Lineu Prestes, 2415 - Butanta, 05508-000 São Paulo-SP, Brazil.

European heart journal

|November 9, 2023

概括

心力衰竭涉及抑制Dicer的4-hydroxynonenal (4-HNE) 的有害影响,损害了microRNA (miRNA) 生产. 激活阿尔代脱酶2 (ALDH2) 清除4-HNE,恢复Dicer功能并改善心力衰竭的结果.

科学领域:

心血管生物学心血管生物学
分子医学是分子医学.
生物化学生物化学

背景情况:

心力衰竭是一个重大的全球健康挑战,需要新的治疗策略.
心力衰竭中的线粒体功能障碍会产生4-hydroxynonenal (4-HNE),一种具有有害作用的反应性化物.

研究的目的:

研究4-HNE影响心力衰竭的机制.
探索针对4-HNE治疗心力衰竭的潜力.

主要方法:

生物化学,功能和体化学分析用于检测人类和老鼠失败的心脏中的4-HNE adducts.
试验室研究验证了4-HNE标,并评估了其对Dicer活性和稳定性的抑制作用.

主要成果:

4-hydroxynonenal (4-HNE) 协同抑制Dicer,Dicer是微RNA (miRNA) 生成至关重要的酶,从而损害了miRNA处理.
人类失败的心脏表现出4-HNE清除受损,Dicer活性降低,和有缺陷的miRNA生物发生.
在临床前心力衰竭模型中,使用Alda-1或AD-9308恢复Dicer活性,miRNA成熟和心脏功能.

结论:

4-HNE直接抑制Dicer,导致心力衰竭中的miRNA生物生成受损.
通过ALDH2激活来降低心脏4-HNE水平,通过恢复Dicer活性和miRNA生物发生,为心力衰竭提供了潜在的治疗策略.

关键词:

化物是一种化物.心脏病是什么心脏病是什么心脏病线粒体中的线粒体.氧化应激是一种氧化应激.治疗疗法治疗疗法

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MicroRNAs

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...