Zinc Overload Induces Damage to H9c2 Cardiomyocyte Through Mitochondrial Dysfunction and ROS-Mediated Mitophagy.

Abstract

Zinc homeostasis is essential for maintaining redox balance, cell proliferation, and apoptosis. However, excessive zinc exposure is toxic and leads to mitochondrial dysfunction. In this study, we established a zinc overload model by treating rat cardiomyocyte H9c2 cells with Zn2+ at different concentrations. Our results showed that zinc overload increased LDH and reactive oxygen species (ROS) levels, leading to cell death, mitochondrial membrane potential decrease and impaired mitochondrial function and dynamics. Furthermore, zinc overload activated the PINK1/Parkin signaling pathway and induced mitochondrial autophagy via ROS, while NAC inhibited mitophagy and weakened the activation of PINK1/Parkin pathway, thereby preserving mitochondrial biogenesis. In addition, our data also showed that Mfn2 deletion increased ROS production and exacerbated cytotoxicity induced by zinc overload. Our results therefore suggest that Zn2+-induced ROS generation causes mitochondrial autophagy and mitochondrial dysfunction, damaging H9c2 cardiomyocytes. Additionally, Mfn2 may play a key role in zinc ion-mediated endoplasmic reticulum and mitochondrial interactions. Our results provide a new perspective on zinc-induced toxicology.

• Authors: Ying Yang, Pei Wang, Jiabao Guo, Tingting Ma, Youcheng Hu, Luyao Huang, Bohan Xing, Yonggui He, Jinkun Xi
• Journal: Cardiovascular toxicology (Cardiovasc Toxicol) Vol. 23 Issue 11-12 Pg. 388-405 (12 2023) ISSN: 1559-0259 [Electronic] United States
• PMID: 37845565 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Reactive Oxygen Species
• Zinc
• Protein Kinases
• Ubiquitin-Protein Ligases

Topics

• Rats
• Animals
• Mitophagy
• Reactive Oxygen Species (metabolism)
• Myocytes, Cardiac (metabolism)
• Zinc (toxicity)
• Protein Kinases (metabolism)
• Mitochondria (metabolism)
• Ubiquitin-Protein Ligases (metabolism)