Cancer treatment-induced NAD+ depletion in premature senescence and late cardiovascular complications.
Cancer treatment-induced NAD+ depletion in premature senescence and late cardiovascular complications.
复制标题
DOI：
10.20517/jca.2022.13
复制
发表时间：
2022-01-01
期刊：
影响因子：
--
通讯作者：
Abe, Jun-Ichi
中科院分区：
文献类型：
--
作者：
Banerjee, Priyanka;Olmsted-Davis, Elizabeth A;Abe, Jun-Ichi
大量研究揭示了各种癌症治疗方式诱导的过早衰老在衰老相关疾病发病机制中的关键作用。端粒功能障碍可诱导衰老相关分泌表型（SASP）。一些癌症治疗所诱导的端粒DNA损伤反应可持续数月，这可能是癌症治疗长期后遗症的原因。端粒DNA损伤诱导的线粒体功能障碍以及活性氧生成增加是过早衰老的标志。最近，我们报道了由p90核糖体S6激酶（p90RSK）和细胞外调节蛋白激酶5（ERK5，丝裂原活化蛋白激酶家族中一个独特成员，它不仅是一种激酶，也是一种转录共激活因子）上S496的磷酸化所形成的核 - 线粒体正反馈回路是重要的信号事件，在连接线粒体功能障碍、核端粒功能障碍、持续性SASP诱导以及动脉粥样硬化中起着至关重要的作用。在这篇综述中，我们将讨论NAD⁺耗竭在引发SASP中的作用及其下游导致癌症幸存者动脉粥样硬化性心血管疾病过早发病的信号和调控机制。
Numerous studies have revealed the critical role of premature senescence induced by various cancer treatment modalities in the pathogenesis of aging-related diseases. Senescence-associated secretory phenotype (SASP) can be induced by telomere dysfunction. Telomeric DNA damage response induced by some cancer treatments can persist for months, possibly accounting for long-term sequelae of cancer treatments. Telomeric DNA damage-induced mitochondrial dysfunction and increased reactive oxygen species production are hallmarks of premature senescence. Recently, we reported that the nucleus-mitochondria positive feedback loop formed by p90 ribosomal S6 kinase (p90RSK) and phosphorylation of S496 on ERK5 (a unique member of the mitogen-activated protein kinase family that is not only a kinase but also a transcriptional co-activator) were vital signaling events that played crucial roles in linking mitochondrial dysfunction, nuclear telomere dysfunction, persistent SASP induction, and atherosclerosis. In this review, we will discuss the role of NAD+ depletion in instigating SASP and its downstream signaling and regulatory mechanisms that lead to the premature onset of atherosclerotic cardiovascular diseases in cancer survivors.