Kordi Negin, Saydi Ali, Azimi Maliheh, Mazdarani Farivar Haji, Gadruni Keivan, Jung Friedrich, Karami Sajad
Department of Exercise Physiology, Faculty of Sport Sciences, Razi University, Kermanshah, Iran.
Faculty of Physical Education, Shahrood University of Technology, Shahrood, Iran.
Clin Hemorheol Microcirc. 2024;88(3):337-350. doi: 10.3233/CH-242329.
Copper is an essential element in the human body, involved in many physiological and metabolic functions, including coagulation, oxidative metabolism, and hormone production. The maintenance of copper homeostasis within cells is a complex procedure that is intrinsically controlled by a multitude of intricate mechanisms. Disorders of copper homeostasis encompass a wide range of pathological conditions, including degenerative neurological diseases, metabolic disorders, cardio-cerebrovascular diseases, and tumors. Cuproptosis, a recently identified non-apoptotic mode of cell death mode, is characterized by copper dependence and the regulation of mitochondrial respiration. Cuproptosis represents a novel form of cell death distinct from the previously described modes, including apoptosis, necrosis, pyroptosis, and ferroptosis. Excess copper has been shown to induce cuproptosis by stimulating protein toxic stress responses via copper-dependent abnormal oligomerization of lipoylation proteins within the tricarboxylic acid cycle and the subsequent reduction of iron-sulfur cluster protein levels. Ferredoxin1 facilitates the lipoacylation of dihydrolipoyl transacetylase, which in turn degrades iron-sulfur cluster proteins by reducing Cu2+ to Cu+, thereby inducing cell death. Furthermore, copper homeostasis is regulated by the copper transporter, and disturbances in this homeostasis result in cuproptosis. Current evidence suggests that cuproptosis plays an important role in the onset and development of several cardiovascular diseases. Copper-chelating agents, including ammonium tetrathiomolybdate (VI) and DL-penicillamine, have been shown to facilitate the alleviation of cardiovascular disease by inhibiting cuproptosis. It is hypothesized that oxidative phosphorylation inhibitors such as physical training may inhibit cuproptosis by inhibiting the protein stress response. In conclusion, the implementation of physical training may be a viable strategy to reducte the incidence of cuproptosis.
铜是人体必需的元素，参与许多生理和代谢功能，包括凝血、氧化代谢和激素产生。细胞内铜稳态的维持是一个复杂的过程，由多种复杂机制内在地控制。铜稳态紊乱包括一系列病理状况，如退行性神经疾病、代谢紊乱、心脑血管疾病和肿瘤。铜死亡是最近发现的一种非凋亡性细胞死亡模式，其特征是铜依赖性和线粒体呼吸的调节。铜死亡代表一种不同于先前描述的细胞死亡模式的新形式，包括凋亡、坏死、焦亡和铁死亡。过量的铜已被证明可通过刺激蛋白质毒性应激反应诱导铜死亡，该反应通过三羧酸循环中脂酰化蛋白的铜依赖性异常寡聚化以及随后铁硫簇蛋白水平的降低来实现。铁氧还蛋白1促进二氢硫辛酰胺转乙酰酶的脂酰化，进而通过将Cu2+还原为Cu+来降解铁硫簇蛋白，从而诱导细胞死亡。此外，铜稳态由铜转运体调节，这种稳态的紊乱会导致铜死亡。目前的证据表明，铜死亡在几种心血管疾病的发生和发展中起重要作用。包括四硫代钼酸铵（VI）和DL-青霉胺在内的铜螯合剂已被证明可通过抑制铜死亡来促进心血管疾病的缓解。据推测，诸如体育锻炼等氧化磷酸化抑制剂可能通过抑制蛋白质应激反应来抑制铜死亡。总之，实施体育锻炼可能是降低铜死亡发生率的可行策略。
