2. Academic Validation
  3. A role of ROS-dependent defects in mitochondrial dynamic and autophagy in carbon black nanoparticle-mediated myocardial cell damage

A role of ROS-dependent defects in mitochondrial dynamic and autophagy in carbon black nanoparticle-mediated myocardial cell damage

  • Free Radic Biol Med. 2024 Apr 30:220:249-261. doi: 10.1016/j.freeradbiomed.2024.04.241.
Zehua Xu 1,  Jing Li 2,  Bowen Su 3,  Hongying Gao 3,  Miaomiao Ren 3,  Yi Lin 4,  Heqing Shen 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory & State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, 361102, PR China. Electronic address: 32620211150853@stu.xmu.edu.cn.
  • 2 State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory & State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, 361102, PR China. Electronic address: leejing@stu.xmu.edu.cn.
  • 3 State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory & State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, 361102, PR China.
  • 4 State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory & State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, 361102, PR China. Electronic address: tjlinyi@xmu.edu.cn.
  • 5 State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory & State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, 361102, PR China; Department of Obstetrics, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, 361003, PR China. Electronic address: hqshen@xmu.edu.cn.
PMID: 38697491 DOI: 10.1016/j.freeradbiomed.2024.04.241
Abstract

Carbon black nanoparticles (CBNPs) are widely distributed in the environment and are increasingly recognized as a contributor in the development of Cardiovascular Disease. A variety of cardiac injuries and diseases result from structural and functional damage to cardiomyocytes. This study explored the mechanisms of CBNPs-mediated myocardial toxicity. CBNPs were given to mice through intra-tracheal instillation and it was demonstrated that the particles can be taken up into the cardiac tissue. Exposure to CBNPs induced cardiomyocyte inflammation and Apoptosis. In combination with in vitro experiments, we showed that CBNPs increased the ROS and induced mitochondria fragmentation. Functionally, CBNPs-exposed cardiomyocyte exhibited depolarization of the mitochondrial membrane potential, release of cytochrome c, and activation of pro-apoptotic Bax, thereby initiating programmed cell death. On the Other hand, CBNPs impaired Autophagy, leading to the inadequate removal of dysfunctional mitochondria. The excess accumulation of damaged mitochondria further stimulated NF-κB activation and triggered the NLRP3 inflammasome pathway. Both the antioxidant N-acetylcysteine and the Autophagy activator rapamycin were effective to attenuate the damage of CBNPs on cardiomyocytes. Taken together, this study elucidated the potential mechanism underlying CBNPs-induced myocardial injury and provided a scientific reference for the evaluation and prevention of the CBNPs-related heart risk.

Keywords

Apoptosis; CBNPs; Cardiomyocyte; Mitochondrial quality control; NF-κB/NLRP3.

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