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心脏缩中的DNA损伤和核形态变化是由SNRK通过乙脱聚变调解的

Paulina J Stanczyk^1,2, Yuki Tatekoshi¹, Jason S Shapiro¹

¹Division of Cardiology, Department of Medicine, and Feinberg Cardiovascular and Renal Research Institute (P.J.S., Y.T., J.S.S., K.N., Y.C., Z.Z., A.D.J., A.M., A.A., H.-C.C., H.A.), Northwestern University School of Medicine, Chicago, IL.

|September 18, 2023

概括

通过与Destrin (DSTN) 相互作用,与SNF1相关的激酶 (SNRK) 会加剧心脏缩和DNA损伤. 这种相互作用破坏了actin聚合,导致核异常和心肌细胞功能受损.

科学领域:

心血管生物学
分子心脏病学
细胞生物学

背景情况:

正确的核组织对于心肌细胞的功能至关重要;核结构重塑与心血管疾病有关.
虽然DNA损伤与心脏缩有关,但根本的机制尚不清楚.
AMP激活蛋白激酶 (AMPK) 家族成员调节新陈代谢和DNA损伤反应 (DDR).

研究的目的:

研究SNF1相关激酶 (SNRK) 在心脏缩和DNA损伤反应 (DDR) 中的作用.
确定SNRK是否影响心肌细胞核结构和功能.
确定SNRK的分子目标和参与心脏重塑的相互作用伙伴.

主要方法:

心脏特异性Snrk淘汰小鼠进行了心脏功能和DDR评估.
在体外研究中调节了SNRK表达,以评估对DDR和核参数的影响.
蛋白组学确定了SNRK的标,同时免疫沉证实了Destrin (DSTN) 是一个具有约束力的合作伙伴.

主要成果:

失败的小鼠表现出心脏功能恶化,心脏缩增加和DDR标志物pH2AX升高.
在体外Snrk的破坏导致DNA损伤增加,染色质的紧缩,以及核形态的改变.
它们的相互作用调节了actin的聚合,影响了DNA的损伤和核的形状.

结论:

通过与DSTN的相互作用,SNRK在心脏缩和DNA损伤中发挥着关键作用.
这种相互作用调节了actin聚合,从而影响了DNA损伤反应和心肌细胞核完整性.
针对SNRK-DSTN途径可能为涉及核异常的心血管疾病提供治疗策略.

关键词:

通过AMP激活的蛋白激酶德斯林其他药物左心室增大肌细胞,心脏

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