School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
School of Basic Medicine Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
Apoptosis. 2024 Aug;29(7-8):981-1006. doi: 10.1007/s10495-024-01983-0. Epub 2024 Jun 2.
Copper is a trace element required by the organism, but once the level of copper exceeds the threshold, it becomes toxic and even causes death. The underlying mechanisms of copper-induced death are inconclusive, with different studies showing different opinions on the mechanism of copper-induced death. Multiple investigations have shown that copper induces oxidative stress, endoplasmic reticulum stress, nucleolar stress, and proteasome inhibition, all of which can result in cell death. The latest research elucidates a copper-dependent death and denominates it as cuproptosis. Cuproptosis takes place through the combination of copper and lipoylated proteins of the tricarboxylic acid cycle, triggering agglomeration of lipoylated proteins and loss of iron-sulfur cluster proteins, leading to proteotoxic stress and ultimately death. Given the toxicity and necessity of copper, abnormal levels of copper lead to diseases such as neurological diseases and cancer. The development of cancer has a high demand for copper, neurological diseases involve the change of copper contents and the binding of copper to proteins. There is a close relationship between these two kinds of diseases and copper. Here, we summarize the mechanisms of copper-related death, and the association between copper and diseases, to better figure out the influence of copper in cell death and diseases, thus advancing the clinical remedy of these diseases.
铜是生物体所需的微量元素,但一旦铜的水平超过阈值,它就会变得有毒,甚至导致死亡。铜诱导死亡的潜在机制尚不清楚,不同的研究对铜诱导死亡的机制有不同的看法。多项研究表明,铜诱导氧化应激、内质网应激、核仁应激和蛋白酶体抑制,所有这些都可能导致细胞死亡。最新的研究阐明了一种依赖铜的死亡,并将其命名为铜死亡。铜死亡通过铜与三羧酸循环的脂酰化蛋白结合发生,引发脂酰化蛋白聚集和铁硫簇蛋白丢失,导致蛋白毒性应激,最终导致死亡。鉴于铜的毒性和必要性,铜的异常水平会导致神经疾病和癌症等疾病。癌症的发展对铜的需求很高,神经疾病涉及铜含量的变化和铜与蛋白质的结合。这两种疾病与铜密切相关。在这里,我们总结了与铜相关的死亡机制,以及铜与疾病的关系,以更好地了解铜在细胞死亡和疾病中的影响,从而推进这些疾病的临床治疗。
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