2. Academic Validation
  3. S-Allyl-L-cysteine (SAC) inhibits copper-induced apoptosis and cuproptosis to alleviate cardiomyocyte injury

S-Allyl-L-cysteine (SAC) inhibits copper-induced apoptosis and cuproptosis to alleviate cardiomyocyte injury

  • Biochem Biophys Res Commun. 2024 Jul 2:730:150341. doi: 10.1016/j.bbrc.2024.150341.
Xiao-Pei Huang 1,  Zan-Hua Shi 2,  Guang-Feng Ming 3,  Dao-Miao Xu 3,  Shu-Qiao Cheng 4
Affiliations

Affiliations

  • 1 Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China; Department of Critical Care Medicine, Henan Provincial People's Hospital (People's Hospital of Zhengzhou University), Zhengzhou, 450003, Henan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
  • 2 Department of Neurosurgery, Xiangya Hospital, Central South University Changsha 410008, Hunan, China.
  • 3 Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
  • 4 Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China; Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China. Electronic address: cheng0203@csu.edu.cn.
PMID: 39018965 DOI: 10.1016/j.bbrc.2024.150341
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.

Keywords

Cardiomyocyte injury; Copper; Cuproptosis; FDX1; S-Allyl-L-cysteine.

Figures
Products