期刊
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
卷 244, 期 -, 页码 -出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ecoenv.2022.114020
关键词
OMDT; C5b-9; Renal tubules; Ca 2+ overload; Ferroptosis
资金
- National Natural Science Foundation of China [81874259, 82173494, 82103728]
- Anhui Medical University [XJ201941]
- Biotechnology and Biological Sciences Research Council (BBSRC) [BB/P004695/1]
- National Institute of Aging (NIA) [1R01AG049321-01A1]
The study aims to explore renal tubular ferroptosis induced by trichloroethylene sensitization and its mechanism. Through observation of the kidneys of trichloroethylene-sensitized mice and HK-2 cells, it was found that C5b-9 and cytosolic Ca2+ overload may play a key role in renal tubular ferroptosis.
Occupational medicamentose-like dermatitis due to trichloroethylene (OMDT) is a key but unresolved question. OMDT patients often present multiple organ damage, including kidney damage. However, the underlying mechanism remains unknown. The purpose of our study was to explore the effect of tubule-specific C5b-9 deposition induced by TCE sensitization on renal tubular ferroptosis and its mechanism. By analyzing patho-logical changes of TCE-sensitization-mice kidney, we observed a significant renal tubular ferroptosis, which was alleviated by CD59, a C5b-9 inhibitory protein. Moreover, this phenomenon was also replicated in a C5b-9-attacked HK-2 cell model. Further experiments identified that C5b-9 induced cytosolic Ca2+ overload in renal tubular epithelia cells from TCE-sensitization-mice and HK-2 cells. Furthermore, in vitro experiments showed that BAPTA-AM, an intracellular Ca2+ chelator, could rescued ferroptosis induced by C5b-9 in HK-2 cells. Taken together, TCE sensitization induced renal tubular ferroptosis is mediated by C5b-9 and cytosolic Ca2+ overload may play a key role.
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