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一个超氧化驱动的氧化还原状态促进日转化和耐老化在复制压力相关的衰老中的耐药性

Le Luo¹, Shazib Pervaiz², Marie-Veronique Clement³

¹Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 117596, Singapore.

|June 7, 2023

概括

一个与细胞衰老相关的新型氧化还原状态,SA-redox状态,是由超氧化物驱动的,而不是过氧化. 这种状态会影响衰老相关的分泌表型和晚期转化,p21发挥着关键作用.

科学领域:

细胞生物学细胞生物学
氧化压力研究研究氧化压力研究
衰老研究研究衰老研究

背景情况:

细胞衰老是一种不可逆转的生长停止状态.
复制压力是已知的细胞衰老诱导因素.
特定的氧化还原状态在衰老中的作用尚未完全理解.

研究的目的:

为了识别和描述与复制压力诱导的衰老相关的新型氧化还原状态.
为了研究这种衰老相关的氧化还原状态的分子机制和功能后果.
探索这种氧化还原状态与关键衰老标志物和途径之间的关系.

主要方法:

使用了与甲基甲硫酸盐治疗的S相同步RPE1-hTERT细胞.
采用超氧化物感应光探针 (二乙,素,米托索克斯) 和基/氧化探针 (HPF).
测量了谷氨 (GSH) 和GSSG水平;使用了超氧化物清除剂Tiron和H2O2抗氧化剂N-乙半氨酸.

主要成果:

鉴定了一种与衰老相关的氧化还原状态 (SA-氧化还原状态),对超氧化物和过氧化/基激素探针有反应,但不是H2O2探针.
SA-redox状态减轻了总GSH水平,并且依赖于超氧化物,正如Tiron的抑制作用所示.
SA-redox状态不参与细胞循环停止或SA-β-Gal活性,但与NF-κB激活,SASP概况,TFEB水平,晚期转化和老化反应有关.
与p53 (减轻建立) 和p21 (加强SA-redox状态在日后转换和老化抵抗中至关重要) 证明了交叉声.

结论:

SA-redox状态是复制压力诱导的衰老的独特的氧化还原特征.
超氧化物,而不是过氧化,是参与建立SA-redox状态的主要反应性氧物种.
SA-redox状态在调节衰老表型方面发挥着重要作用,包括SASP和日后转换,其调节涉及p53和p21.

关键词:

转换时代的转换过氧化酸盐的过氧酸盐复制压力-复制压力衰老是一种衰老.衰老分析 (Senolysis) 是一个非常重要的过程.这是一种超氧化物.

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