Treatment of acetaminophen-induced liver failure by blocking the death checkpoint protein TRAIL

Chen, Qian; Yan, Dehong; Zhang, Qingmei; Zhang, Guizhong; Xia, Meng; Li, Junxin; Zhan, Wugen; Shen, Enyun; Li, Zhihuan; Lin, Lilong; Chen, Youhai H.; Wan, Xiaochun

doi:10.1016/j.bbadis.2019.165583

Cited by 8 publications

(8 citation statements)

References 42 publications

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“…APAP toxicity is associated with many common events including apoptosis [25]. The current results display that mice treated with APAP show significant increase in protein expression of cleaved caspase-3 around CV.…”

Section: Abdel-bakky Ms Et Alsupporting

confidence: 52%

Loss of RAR-α and RXR-α and enhanced caspase-3-dependent apoptosis in N-acetyl-p-aminophenol-induced liver injury in mice is tissue factor dependent

Abdel-Bakky

Helal

El-Sayed

et al. 2021

Korean J Physiol Pharmacol

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Section: Abdel-bakky Ms Et Alsupporting

confidence: 52%

Loss of RAR-α and RXR-α and enhanced caspase-3-dependent apoptosis in N-acetyl-p-aminophenol-induced liver injury in mice is tissue factor dependent

Abdel-Bakky

Helal

El-Sayed

et al. 2021

Korean J Physiol Pharmacol

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“…It was reported that the endoplasmic reticulum (ER) stress-inducible transcription factor CHOP induced cell death and was an important factor in the pathogenesis of different disease mouse models [ 19 , 38 , 39 , 40 , 41 , 42 ]. To investigate the effect of Mito-T on the expression of CHOP after APAP-induced liver injury, Mito-T (20 mg/kg, i.p.)…”

Section: Resultsmentioning

confidence: 99%

The Late-Stage Protective Effect of Mito-TEMPO against Acetaminophen-Induced Hepatotoxicity in Mouse and Three-Dimensional Cell Culture Models

et al. 2020

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An overdose of acetaminophen (APAP), the most common cause of acute liver injury, induces oxidative stress that subsequently causes mitochondrial impairment and hepatic necroptosis. N-acetyl-L-cysteine (NAC), the only recognized drug against APAP hepatotoxicity, is less effective the later it is administered. This study evaluated the protective effect of mitochondria-specific Mito-TEMPO (Mito-T) on APAP-induced acute liver injury in C57BL/6J male mice, and a three dimensional (3D)-cell culture model containing the human hepatoblastoma cell line HepG2. The administration of Mito-T (20 mg/kg, i.p.) 1 h after APAP (400 mg/kg, i.p.) injection markedly attenuated the APAP-induced elevated serum transaminase activity and hepatic necrosis. However, Mito-T treatment did not affect key factors in the development of APAP liver injury including the activation of c-jun N-terminal kinases (JNK), and expression of the transcription factor C/EBP homologous protein (CHOP) in the liver. However, Mito-T significantly reduced the APAP-induced increase in the hepatic oxidative stress marker, nitrotyrosine, and DNA fragmentation. Mito-T markedly attenuated cytotoxicity induced by APAP in the HepG2 3D-cell culture model. Moreover, liver regeneration after APAP hepatotoxicity was not affected by Mito-T, demonstrated by no changes in proliferating cell nuclear antigen formation. Therefore, Mito-T was hepatoprotective at the late-stage of APAP overdose in mice.

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“…CHOP contains N‐terminal transcriptional activation domain and C‐terminal basic‐leucine zipper (bZIP) domain composing of a basic amino‐acid‐rich DNA‐binding region, mutant analysis of CHOP confirmed that bZIP domain plays an important role for CHOP‐induced activation of other genes such as DR5 38,39 . In the model of acetaminophen‐induced liver failure, CHOP sensitized TRAIL‐induced apoptosis via inducing of DR5 transcription 40 . Moreover, it is robustly expressed due to genotoxic stress caused by some toxic elements 41 .…”

Section: Discussionmentioning

confidence: 99%

ROS‐mediated PERK‐eIF2α‐ATF4 pathway plays an important role in arsenite‐induced L‐02 cells apoptosis via regulating CHOP‐DR5 signaling

Liu

Zhang

2020

Environmental Toxicology

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Chronic exposure to arsenic remains a worldwide environmental health issue, affecting hundreds of millions of people. Although, arsenic‐induced oxidative stress and apoptosis have been determined, the underlying apoptosis mechanism has not been fully elucidated yet. Oxidative stress integrated‐ER stress plays an important role in Life‐and‐Death decision of cells. The current study was to investigate whether NaAsO2 utilizes oxidative stress integrated‐ER stress signaling to exert pro‐apoptotic activity in L‐02 cells. Results showed that death receptor 5 (DR5) was a mediator of NaAsO2‐induced apoptosis by enhancing construction of the death‐inducing signaling complex (DISC). NaAsO2‐sensitized DR5 elevation required maintainable transcription and its transcription factor C/EBP homologous protein (CHOP). Further results showed that NaAsO2 increased expression in biomarker of endoplasmic reticulum (ER) stress and activated the protein kinase R‐like ER kinase (PERK)‐eukaryotic translation initiation 2α (eIF2α)‐activating transcription factor 4 (ATF4) pathway. PERK inhibitor and ATF4 siRNA significantly attenuated NaAsO2‐induced CHOP and DR5 expressions. In addition, the antioxidant N‐acetyl‐l‐cysteine (NAC) treatment led to amelioration of NaAsO2‐induced production of reactive oxygen species (ROS) and some ER stress‐ and apoptosis‐ related protein levels and cell viability. Taken together, the results indicate that ROS‐mediated PERK‐eIF2α‐ATF4 pathway activated by NaAsO2 is the critical upstream event for subsequent apoptosis induction via regulating CHOP‐DR5 signaling in L‐02 cells when chronic exposure to arsenic, and support that antioxidants might be potential therapeutic agents for preventing or delaying the onset and progress of arsenic‐induced hepatotoxicity.

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Treatment of acetaminophen-induced liver failure by blocking the death checkpoint protein TRAIL

Cited by 8 publications

References 42 publications

Loss of RAR-α and RXR-α and enhanced caspase-3-dependent apoptosis in N-acetyl-p-aminophenol-induced liver injury in mice is tissue factor dependent

Loss of RAR-α and RXR-α and enhanced caspase-3-dependent apoptosis in N-acetyl-p-aminophenol-induced liver injury in mice is tissue factor dependent

The Late-Stage Protective Effect of Mito-TEMPO against Acetaminophen-Induced Hepatotoxicity in Mouse and Three-Dimensional Cell Culture Models

ROS‐mediated PERK‐eIF2α‐ATF4 pathway plays an important role in arsenite‐induced L‐02 cells apoptosis via regulating CHOP‐DR5 signaling

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