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Environmental arsenic pollution induced liver oxidative stress injury by regulating miR-155 through inhibition of AUF1.
- Source :
-
The Science of the total environment [Sci Total Environ] 2024 Apr 20; Vol. 922, pp. 171237. Date of Electronic Publication: 2024 Feb 27. - Publication Year :
- 2024
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Abstract
- Arsenic (As), a common environmental pollutant, has become a hot topic in recent years due to its potentially harmful effects. Liver damage being a central clinical feature of chronic arsenic poisoning. However, the underlying mechanisms remain unclear. We demonstrated that arsenic can lead to oxidative stress in the liver and result in structural and functional liver damage, significantly correlated with the expression of AUF1, Dicer1, and miR-155 in the liver. Interestingly, knockdown AUF1 promoted the up-regulatory effects of arsenic on Dicer1 and miR-155 and the inhibitory effects on SOD1, which exacerbated oxidative damage in rat liver. However, overexpression of AUF1 reversed the up-regulatory effects of arsenic on Dicer1 and miR-155, restored arsenic-induced SOD1 depletion, and attenuated liver oxidative stress injury. Further, we verified the mechanism and targets of miR-155 in regulating SOD1 by knockdown/overexpression of miR-155 and nonsense mutant SOD1 3'UTR experiments. In conclusion, these results powerfully demonstrate that arsenic inhibits AUF1 protein expression, which in turn reduces the inhibitory effect on Dicer1 expression, which promotes miR-155 to act on the SOD1 3'UTR region after high expression, thus inhibiting SOD1 protein expression and enzyme activity, and inducing liver injury. This finding provides a new perspective for the mechanism research and targeted prevention of arsenic poisoning, as well as scientific evidence for formulating strategies to prevent and control environmental arsenic pollution.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024. Published by Elsevier B.V.)
- Subjects :
- Animals
Rats
3' Untranslated Regions
DEAD-box RNA Helicases metabolism
DEAD-box RNA Helicases pharmacology
Oxidative Stress
Ribonuclease III genetics
Ribonuclease III metabolism
Ribonuclease III pharmacology
Superoxide Dismutase-1 metabolism
Superoxide Dismutase-1 pharmacology
Arsenic toxicity
Arsenic Poisoning prevention & control
Liver drug effects
Liver metabolism
MicroRNAs metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1879-1026
- Volume :
- 922
- Database :
- MEDLINE
- Journal :
- The Science of the total environment
- Publication Type :
- Academic Journal
- Accession number :
- 38423337
- Full Text :
- https://doi.org/10.1016/j.scitotenv.2024.171237