Biotoxicity of paraquat to lung cells mediated by endoplasmic reticulum-mitochondria interaction.

Autor: Xiao P; Clinical Laboratory, Tianjin First Central Hospital, Tianjin, 300192, China., Wu S; Clinical Laboratory, Tianjin First Central Hospital, Tianjin, 300192, China., Wang Z; Department of Emergency, Tianjin First Central Hospital, Tianjin, 300192, China., Shen G; Department of Emergency, Tianjin First Central Hospital, Tianjin, 300192, China., Shi X; Department of Emergency, Tianjin First Central Hospital, Tianjin, 300192, China. sxf74@sohu.com.
Jazyk: angličtina
Zdroj: Journal of molecular histology [J Mol Histol] 2024 Dec; Vol. 55 (6), pp. 1063-1077. Date of Electronic Publication: 2024 Aug 31.
DOI: 10.1007/s10735-024-10249-7
Abstrakt: The high lethality caused by paraquat (PQ) poisoning has attracted much attention in public and human health due to its high toxicity and lethality. However, the understanding of the mechanism of PQ-induced apoptosis from the perspective of organelles, especially inter-organelle interactions, is still scarce. Exploring the linkage of multiple organelles during PQ poisoning and the molecular mechanisms of PQ poisoning under its mediation will help to gain insight into the mode of PQ poisoning at the organelle level. In this study, we observed that a certain dose of PQ gavage induced oxidative stress, mitochondrial dysfunction and endoplasmic reticulum stress in rat lung tissue cells. PQ toxicity led to the occurrence of Ca 2+ overload in the endoplasmic reticulum, and the activated BIP and CHOP pathways directly/indirectly led to the expression of apoptogenic factors Caspase family factors. In addition, PQ promoted Ca 2+ release from the endoplasmic reticulum and Ca 2+ uptake by mitochondria, which induced the disruption of Bax/Bcl-2 channel proteins in response to the IP 3 R/RyR/VDAC1&2/MCU Ca 2+ axis thereby leading to the release of CytoC, which ultimately induced endoplasmic reticulum stress and apoptotic cell death. In addition, 10 differential proteins were screened and validated by proteomics that may act as upstream and downstream active factors of mitochondria-endoplasmic reticulum interaction-mediated biotoxicity. Our findings provide new perspectives for researchers to explore the toxicity mechanisms of PQ to reduce their adverse effects.
Competing Interests: Declarations Conflict of interest This manuscript has not been published in whole or in part and is not being considered for publication elsewhere. This manuscript does not violate or infringe upon any existing copyright/s or license/s from any third party. All authors contributed significantly to the work and are in agreement with the content of the manuscript. There are no conflicts of interests. Ethical Approval This manuscript contains any studies with animals performed by any of the authors. The experimental patients followed the regulations of the Experimental Ethics Committee of the Tianjin First Central Hospital. Consent for publication This manuscript has not been published in whole or in part and is not being considered for publication elsewhere. This manuscript does not violate or infringe upon any existing copyright/s or license/s from any third party. All authors contributed significantly to the work and are in agreement with the content of the manuscript. All the authors gave their consent to the publication of this manuscript.
(© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)
Databáze: MEDLINE
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