CaMKII at the crossroads: calcium dysregulation, and post-translational modifications driving cell death.

IF 4.4 2区 医学 Q1 NEUROSCIENCES Journal of Physiology-London Pub Date : 2025-02-05 DOI:10.1113/JP285941
Alicia Mattiazzi, Carolina Jaquenod De Giusti, Carlos A Valverde
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Abstract

The multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMKII) regulates numerous proteins involved in excitation-contraction-relaxation coupling and cardiac excitability. However, its overactivation induces severe Ca2+/handling alterations, playing a significant role in the pathogenesis of diseases such as hypertrophy, arrhythmias and cell death, which can ultimately lead to heart failure. Being a suitable target for various aberrant signals that characterize several diseases, such as Ca2+ overload, oxidative stress or excessive glycosylation, CaMKII shifts under these conditions from a physiological regulator to a pathological molecule. In this review, we explore the evolution of knowledge regarding the role of CaMKII activation on cell death across different pathological contexts, focusing on the converging mechanisms that transform the enzyme from an ally into a villain.

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十字路口的CaMKII:钙失调和翻译后修饰驱动细胞死亡。
多功能Ca2+/钙调素依赖性蛋白激酶II (CaMKII)调节许多参与兴奋-收缩-松弛耦合和心脏兴奋性的蛋白质。然而,它的过度激活诱导严重的Ca2+/处理改变,在肥厚、心律失常和细胞死亡等疾病的发病机制中发挥重要作用,最终导致心力衰竭。作为表征多种疾病(如Ca2+超载、氧化应激或过度糖基化)的各种异常信号的合适靶标,CaMKII在这些条件下从生理调节剂转变为病理分子。在这篇综述中,我们探讨了关于CaMKII激活在不同病理背景下细胞死亡中的作用的知识的演变,重点是将酶从盟友转变为恶棍的趋同机制。
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来源期刊
Journal of Physiology-London
Journal of Physiology-London 医学-神经科学
CiteScore
9.70
自引率
7.30%
发文量
817
审稿时长
2 months
期刊介绍: The Journal of Physiology publishes full-length original Research Papers and Techniques for Physiology, which are short papers aimed at disseminating new techniques for physiological research. Articles solicited by the Editorial Board include Perspectives, Symposium Reports and Topical Reviews, which highlight areas of special physiological interest. CrossTalk articles are short editorial-style invited articles framing a debate between experts in the field on controversial topics. Letters to the Editor and Journal Club articles are also published. All categories of papers are subjected to peer reivew. The Journal of Physiology welcomes submitted research papers in all areas of physiology. Authors should present original work that illustrates new physiological principles or mechanisms. Papers on work at the molecular level, at the level of the cell membrane, single cells, tissues or organs and on systems physiology are all acceptable. Theoretical papers and papers that use computational models to further our understanding of physiological processes will be considered if based on experimentally derived data and if the hypothesis advanced is directly amenable to experimental testing. While emphasis is on human and mammalian physiology, work on lower vertebrate or invertebrate preparations may be suitable if it furthers the understanding of the functioning of other organisms including mammals.
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