Dataset Information

Proteomics Unravels Emodin Causes Liver Oxidative Damage Elicited by Mitochondrial Dysfunction.

ABSTRACT: Emodin is one of the main active compounds in many Chinese traditional herbs. Due to its potential toxic effect on the liver, the possible injury mechanism needs to be explored. In the present study, we investigated liver injury mechanisms of emodin on rats by the technology of proteomics. Firstly, 4530 proteins were identified from the liver of rats treated with emodin by label free proteomics. Inside, 892 differential proteins were selected, presenting a downward trend. Bioinformatics analysis showed that proteins interfered with by emodin were mainly involved in oxidation-reduction biological processes and mitochondrial metabolic pathways, such as mitochondrial fatty acid ?-oxidation, citric acid cycle, and oxidative phosphorylation, which were further confirmed by western blot. The decrease in maximal respiration, ATP production, spare respiratory capacity, and coupling efficiency and increase in proton leakage were detected by seahorse XFe 24 analyzer, which confirmed the damage of mitochondrial function. The down-regulated expressions in antioxidant proteins were verified by western blot and a significant increase of ROS levels were detected in emodin group, which showed that emodin disrupted redox homeostasis in livers. Molecular docking revealed that the main targets of emodin might be acadvl and complex IV. Generally, emodin could induce oxidative stress in livers by directly targeting acadvl/complex IV and inhibiting fatty acid ?-oxidation, citric acid cycle, and oxidative phosphorylation taken place in mitochondria.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC7201015 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Proteomics Unravels Emodin Causes Liver Oxidative Damage Elicited by Mitochondrial Dysfunction.

Zhang Yinhuan Y Yang Xiaowei X Jia Zhixin Z Liu Jie J Yan Xiaoning X Dai Yihang Y Xiao Hongbin H

Frontiers in pharmacology 20200429

Emodin is one of the main active compounds in many Chinese traditional herbs. Due to its potential toxic effect on the liver, the possible injury mechanism needs to be explored. In the present study, we investigated liver injury mechanisms of emodin on rats by the technology of proteomics. Firstly, 4530 proteins were identified from the liver of rats treated with emodin by label free proteomics. Inside, 892 differential proteins were selected, presenting a downward trend. Bioinformatics analysis ...[more]

PMID: 32410985

Similar Datasets

Project description:Genetic and idiopathic forms of Parkinson's disease (PD) are characterized by loss of dopamine (DA) neurons and typically the formation of protein inclusions containing the alpha-synuclein (α-syn) protein. Environmental contributors to PD remain largely unresolved but toxins, such as paraquat or rotenone, represent well-studied enhancers of susceptibility. Previously, we reported that a bacterial metabolite produced by Streptomyces venezuelae caused age- and dose-dependent DA neurodegeneration in Caenorhabditis elegans and human SH-SY5Y neurons. We hypothesized that this metabolite from a common soil bacterium could enhance neurodegeneration in combination with PD susceptibility gene mutations or toxicants. Here, we report that exposure to the metabolite in C. elegans DA neurons expressing human α-syn or LRRK2 G2019S exacerbates neurodegeneration. Using the PD toxin models 6-hydroxydopamine and rotenone, we demonstrate that exposure to more than one environmental risk factor has an additive effect in eliciting DA neurodegeneration. Evidence suggests that PD-related toxicants cause mitochondrial dysfunction, thus we examined the impact of the metabolite on mitochondrial activity and oxidative stress. An ex vivo assay of C. elegans extracts revealed that this metabolite causes excessive production of reactive oxygen species. Likewise, enhanced expression of a superoxide dismutase reporter was observed in vivo. The anti-oxidant probucol fully rescued metabolite-induced DA neurodegeneration, as well. Interestingly, the stress-responsive FOXO transcription factor DAF-16 was activated following exposure to the metabolite. Through further mechanistic analysis, we discerned the mitochondrial defects associated with metabolite exposure included adenosine triphosphate impairment and upregulation of the mitochondrial unfolded protein response. Metabolite-induced toxicity in DA neurons was rescued by complex I activators. RNA interference (RNAi) knockdown of mitochondrial complex I subunits resulted in rescue of metabolite-induced toxicity in DA neurons. Taken together, our characterization of cellular responses to the S. venezuelae metabolite indicates that this putative environmental trigger of neurotoxicity may cause cell death, in part, through mitochondrial dysfunction and oxidative stress.

Dataset Information

Proteomics Unravels Emodin Causes Liver Oxidative Damage Elicited by Mitochondrial Dysfunction.

Publications

Proteomics Unravels Emodin Causes Liver Oxidative Damage Elicited by Mitochondrial Dysfunction.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets