Exposure to zinc induces lysosomal-mitochondrial axis-mediated apoptosis in PK-15 cells.

Abstract

Zinc (Zn), a kind of metallic element, can cause poisonous effects on host physiology when its excess exposure. Lysosomes and mitochondria are the toxic targets of heavy metals, and the lysosomal-mitochondrial axis is also verified to take part in apoptosis, but the related underlying mechanisms in Zn-induced cytotoxicity remain undefined. Here, we identified that excess Zn could cause cell damage in PK-15 cells accompanied by the lysosomal and mitochondrial dysfunction, with the evidence by the elevated levels of cathepsin B/D (CTSB/CTSD) in cytoplasm and decrease of Lyso-Tracker Red signal, red fluorescence intensity of AO staining, mitochondrial complex enzyme activities and ATP production. Additionally, the number of Annexin V+/PI--stained cells, apoptosis-related genes (Bax, Bid, Bak1, Caspase-9, and Caspase-3) and proteins levels of Bax, Bak1, Caspase-9, cleaved Caspase-3 and cytoplasmic Cyt C were signally elevated under Zn exposure, while the protein levels of Bcl2 and mitochondrial Cyt C were observably decreased. Importantly, Pepstatin A (the activity inhibitor of CTSD) and RNA interference of CTSD (si-CTSD) was used to reduce the release of lysosomal CTSD to the cytoplasm, which could signally alleviated Zn-induced mitochondrial damage and apoptosis. In summary, these results suggested that Zn could induced lysosomal and mitochondrial dysfunction in PK-15 cells, and the CTSD played an important role in Zn-induced lysosomal-mitochondrial axis-mediated apoptosis. Our results provided a new insight in Zn-induced toxicology, which for protecting the ecological environment and public health.

• Authors: Qingwen Yang, Yudong Fang, Chuanshi Zhang, Xuesong Liu, Youhua Wu, Yi Zhang, Junjie Yang, Kang Yong
• Journal: Ecotoxicology and environmental safety (Ecotoxicol Environ Saf) Vol. 241 Pg. 113716 (Aug 2022) ISSN: 1090-2414 [Electronic] Netherlands
• PMID: 35667309 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• bcl-2-Associated X Protein
• Caspase 3
• Caspase 9
• Zinc

Topics

• Apoptosis
• Caspase 3 (metabolism)
• Caspase 9 (metabolism)
• Lysosomes
• Mitochondria
• Zinc (metabolism)
• bcl-2-Associated X Protein (genetics, metabolism)