Abstract：
Cardiomyocyte injury is closely related to various myocardial diseases, and S-Allyl-L-cysteine (SAC) has been found to have myocardial protective effects, but its mechanism is currently unclear. Meanwhile, copper also has various physiological functions, and this study found that copper inhibited cell viability in a concentration and time-dependent manner, and was associated with multiple modes of death. Elesclomol plus CuCl2 (ES + Cu) significantly inhibited cell viability, and this effect could only be blocked by copper chelator TTM, indicating that \"ES + Cu\" induced cuproptosis in cardiomyocytes. SAC reduced the inhibitory effects of high concentration copper and \"ES + Cu\" on cell viability in a concentration and time-dependent manner, indicating that SAC plays a cardioprotective role under stress. Further mechanism study showed that high concentration of copper significantly induced cardiomyocyte apoptosis and increased the levels of LDH, MDA and ROS, while SAC inhibited the apoptosis and injury of cardiomyocytes induced by copper. \"ES + Cu\" significantly increased intracellular copper levels and decreased the expression of FDX1, LIAS, Lip-DLST and Lip-DLAT; FDX1 siRNA did not affect the expression of LIAS, but further reduced the expression of Lip-DLST and Lip-DLAT; SAC did not affect the expression of these genes, but enhanced the effect of \"ES + Cu\" in down-regulating these gene expression and restored intracellular copper levels. In addition, \"ES + Cu\" reduced ATP production, weakened the activity of mitochondrial complex I and III, inhibited cell viability, and increased the contents of injury markers LDH, MDA, CK-MB and cTnI, while SAC significantly improved mitochondrial function injury and cardiomyocyte injury induced by \"ES + Cu\". Therefore, SAC can inhibit apoptosis and cuproptosis to play a cardioprotective role.
摘要：
心肌细胞损伤与各种心肌疾病密切相关。和S-烯丙基-L-半胱氨酸（SAC）已被发现具有心肌保护作用，但其机制目前尚不清楚。同时,铜还具有各种生理功能，这项研究发现，铜以浓度和时间依赖性的方式抑制细胞活力，并与多种死亡模式有关。elesclomol加CuCl2(ES+Cu)显著抑制细胞活力,这种作用只能被铜螯合剂TTM阻断，表明“ES+Cu”诱导心肌细胞凋亡。SAC以浓度和时间依赖性方式降低了高浓度铜和“ES+Cu”对细胞活力的抑制作用，表明SAC在压力下发挥心脏保护作用。进一步的机制研究表明,高浓度铜显著诱导心肌细胞凋亡,增加LDH,MDA和ROS，SAC抑制铜诱导的心肌细胞凋亡和损伤。“ES+Cu”显著增加细胞内铜水平，降低FDX1、LIAS、Lip-DLST和Lip-DLAT；FDX1siRNA不影响LIAS的表达，但进一步降低Lip-DLST和Lip-DLAT的表达；SAC不影响这些基因的表达，但增强了“ESCu”下调这些基因表达并恢复细胞内铜水平的作用。此外,“ES+Cu”减少了ATP产量，削弱了线粒体复合物I和III的活性，抑制细胞活力，增加了损伤标志物LDH的含量，MDA,CK-MB和cTnI,而SAC明显改善“ES+Cu”诱导的线粒体功能损伤和心肌细胞损伤。因此,SAC可以抑制细胞凋亡和细胞凋亡，发挥心脏保护作用。
