jf0c00534_si_001.pdf (530.09 kB)
Lysosomal Reacidification Ameliorates Vinyl Carbamate-Induced Toxicity and Disruption on Lysosomal pH
journal contribution
posted on 2020-08-07, 13:37 authored by Yuting Li, Dongwen Hu, Jifeng Qi, Sunliang Cui, Wei ChenEthyl carbamate (EC) is a carcinogen
toxicant, commonly found in
fermented foods and beverages. The carcinogenic and toxic possibility
of EC is thought to be related to its metabolite vinyl carbamate (VC).
However, we found interesting mechanisms underlying VC-induced toxicity
in this study, which were greatly different from EC. We first conducted
a simple synthesis procedure for VC and found that VC possessed higher
toxicity but failed to regulate levels of reactive oxygen species,
glutathione, and autophagy. Notably, VC treatment resulted in upregulation
of lysosomal pH, which was responsible for its cytotoxicity. Cyclic
adenosine monophosphate (cAMP) pretreatment could enhance restoration
of lysosomal acidity and ameliorate VC-induced damage. Inhibition
of protein kinase A and cystic fibrosis transmembrane conductance
regulator can block cAMP-induced cytoprotection. Together, our results
provided the evidence for novel mechanisms of toxicity and possible
protection method under VC exposure, which might give new perspectives
on the study of EC-induced toxicity.
History
Usage metrics
Categories
Keywords
EC-induced toxicityameliorate VC-induced damageprotection methodsynthesis procedureLysosomal Reacidification Ameliorat...fibrosis transmembrane conductance ...novel mechanismslysosomal pHmetabolite vinyl carbamateLysosomal pH Ethyl carbamateprotein kinaseVC treatmentCyclic adenosine monophosphateVC-induced toxicitycAMP-induced cytoprotectionlysosomal acidityreactive oxygen speciesVC exposurecarcinogen toxicant
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC