{"title":"Cell death induced by acute kidney injury: A perspective on the contributions of accidental and programmed cell death.","authors":"Mi Ra Noh, Babu Padanilam","doi":"10.1152/ajprenal.00275.2023","DOIUrl":null,"url":null,"abstract":"The involvement of cell death in AKI is linked to multiple factors including nucleotide depletion, electrolyte imbalance, reactive oxygen species, endonucleases, disturbance of mitochondrial integrity, and activation of several cell death pathway components. Since our review in 2003, discussing the relative contributions of apoptosis and necrosis, several other forms of cell death have been identified and are shown to contribute to acute kidney injury (AKI). Currently, these various forms of cell death can be fundamentally divided into accidental cell death (ACD) and regulated or programmed cell death (RCD/PCD) based on functional aspects. Several death initiator and effector molecules, switch molecules that may act as signaling components triggering either death or protective mechanisms or alternate cell death pathways have been identified as part of the machinery. Intriguingly, several of these cell death pathways share components and signaling pathways suggesting complementary or compensatory functions. Thus defining the crosstalk between distinct cell death pathways and identifying the unique molecular effectors for each type of cell death may be required to develop novel strategies to prevent cell death. Further, depending on the multiple forms of cell death simultaneously induced in different AKI settings, strategies for combination therapies that block multiple cell death pathways need to be developed to completely prevent injury, cell death and renal function. This review highlights the various cell death pathways, crosstalk and interactions between different cell death modalities in AKI.","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"American journal of physiology. Renal physiology","FirstCategoryId":"0","ListUrlMain":"https://doi.org/10.1152/ajprenal.00275.2023","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
The involvement of cell death in AKI is linked to multiple factors including nucleotide depletion, electrolyte imbalance, reactive oxygen species, endonucleases, disturbance of mitochondrial integrity, and activation of several cell death pathway components. Since our review in 2003, discussing the relative contributions of apoptosis and necrosis, several other forms of cell death have been identified and are shown to contribute to acute kidney injury (AKI). Currently, these various forms of cell death can be fundamentally divided into accidental cell death (ACD) and regulated or programmed cell death (RCD/PCD) based on functional aspects. Several death initiator and effector molecules, switch molecules that may act as signaling components triggering either death or protective mechanisms or alternate cell death pathways have been identified as part of the machinery. Intriguingly, several of these cell death pathways share components and signaling pathways suggesting complementary or compensatory functions. Thus defining the crosstalk between distinct cell death pathways and identifying the unique molecular effectors for each type of cell death may be required to develop novel strategies to prevent cell death. Further, depending on the multiple forms of cell death simultaneously induced in different AKI settings, strategies for combination therapies that block multiple cell death pathways need to be developed to completely prevent injury, cell death and renal function. This review highlights the various cell death pathways, crosstalk and interactions between different cell death modalities in AKI.
细胞死亡参与 AKI 与多种因素有关,包括核苷酸耗竭、电解质失衡、活性氧、核酸内切酶、线粒体完整性紊乱以及多种细胞死亡途径成分的激活。我们在 2003 年的综述中讨论了细胞凋亡和坏死的相对作用,自那以后,我们又发现了其他几种细胞死亡形式,并证明它们是造成急性肾损伤(AKI)的原因。目前,这些不同形式的细胞死亡可根据功能方面基本分为意外细胞死亡(ACD)和受调控或程序性细胞死亡(RCD/PCD)。作为该机制的一部分,一些死亡启动子和效应分子、开关分子已被确认,它们可作为信号元件触发死亡或保护机制或交替细胞死亡途径。耐人寻味的是,这些细胞死亡途径中有几种共享成分和信号途径,这表明它们具有互补或补偿功能。因此,要开发预防细胞死亡的新策略,可能需要明确不同细胞死亡途径之间的相互影响,并确定每种细胞死亡的独特分子效应器。此外,根据不同 AKI 情况下同时诱发的多种细胞死亡形式,需要开发阻断多种细胞死亡途径的联合疗法策略,以彻底预防损伤、细胞死亡和肾功能。本综述重点介绍了 AKI 中的各种细胞死亡途径、不同细胞死亡方式之间的相互影响和相互作用。