Related Experiment Video
Updated: Apr 18, 2026
Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
Published on: January 22, 2019
Troxerutin inhibits 2,2',4,4'-tetrabromodiphenyl ether (BDE-47)-induced hepatocyte apoptosis by restoring proteasome
Zi-Feng Zhang1, Qun Shan1, Juan Zhuang2
1School of Environment Science and Spatial Informatics, China University of Mining and Technology, Xuzhou 221116, Jiangsu Province, PR China; Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, Xuzhou 221116, Jiangsu Province, PR China.
Abstract:
Proteasome dysfunction has been associated with the pathogeneses of a variety of diseases and with the neurotoxicities of environmental chemicals; however, whether proteasome dysfunction plays a role in the cellular toxicity of polybrominated diphenyl ethers (PBDEs) has not been investigated to date. Emerging evidence suggests that antioxidants exhibit evident beneficial effects on the cellular toxicity associated with PBDEs. In the present study, we investigated whether troxerutin attenuates BDE-47-induced hepatocyte apoptosis by restoring proteasome function and explored the mechanisms underlying this effect. Our results revealed that proteasome dysfunction was involved in the BDE-47-induced hepatocyte apoptosis in the mouse liver. Furthermore, our results revealed that troxerutin effectively inhibited hepatocyte apoptosis by restoring oxidative stress-mediated proteasome dysfunction in BDE-47-treated mice. Consequently, troxerutin markedly suppressed endoplasmic reticulum (ER) stress in the livers of the BDE-47-treated mice. The inhibitory effects of troxerutin on ER stress and apoptotic pathways were markedly blunted by treatment with epoxomicin (a selective inhibitor of proteasome). Ultimately, troxerutin dramatically blocked TRAF2-ASK1-JNK signaling and CHOP-mediated apoptosis signaling in the BDE-47-treated mouse livers. This study provides novel mechanistic insights into the toxicity of BDE-47 and indicates that troxerutin might be a candidate for the prevention of and therapy for BDE-47-induced hepatotoxicity.
Insights
Troxerutin protects liver cells from BDE-47 toxicity by restoring proteasome function and reducing oxidative stress and endoplasmic reticulum stress. This suggests troxerutin may help prevent BDE-47-induced liver damage.
Area of Science:
- Toxicology
- Cell Biology
- Biochemistry
Background:
- Proteasome dysfunction is linked to diseases and chemical toxicities.
- Polybrominated diphenyl ethers (PBDEs) are environmental chemicals with emerging evidence of cellular toxicity.
- Antioxidants show promise in mitigating PBDE-induced cellular damage.
Purpose of the Study:
- To investigate if troxerutin can alleviate BDE-47-induced hepatocyte apoptosis.
- To determine if troxerutin restores proteasome function in the context of BDE-47 exposure.
- To elucidate the underlying mechanisms of troxerutin's protective effects against BDE-47 toxicity.
Main Methods:
- Assessing proteasome function and hepatocyte apoptosis in BDE-47-treated mouse livers.
- Evaluating the impact of troxerutin on oxidative stress and endoplasmic reticulum (ER) stress markers.
- Utilizing epoxomicin, a proteasome inhibitor, to confirm troxerutin's mechanism of action.
- Analyzing key signaling pathways including TRAF2-ASK1-JNK and CHOP-mediated apoptosis.
Main Results:
- BDE-47 exposure induced proteasome dysfunction and hepatocyte apoptosis in mouse livers.
- Troxerutin treatment restored proteasome function, attenuated oxidative stress, and suppressed ER stress.
- The protective effects of troxerutin were diminished by epoxomicin, confirming the role of proteasome restoration.
- Troxerutin effectively inhibited BDE-47-induced apoptosis by blocking TRAF2-ASK1-JNK and CHOP signaling.
Conclusions:
- Proteasome dysfunction is implicated in BDE-47-induced hepatotoxicity.
- Troxerutin mitigates BDE-47 hepatotoxicity by restoring proteasome function and reducing oxidative and ER stress.
- Troxerutin demonstrates potential as a therapeutic agent for BDE-47-induced liver injury.
More Related Videos
19:44Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen
Published on: May 30, 2012
09:18Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
Published on: December 27, 2016
Related Concept Videos
01:31The Intrinsic Apoptotic Pathway
02:23Abnormal Proliferation