TRAIL enhances paracetamol-induced liver sinusoidal endothelial cell death in a Bim- and Bid-dependent manner.

Abstract:

:Paracetamol (acetaminophen, APAP) is a universally used analgesic and antipyretic agent. Considered safe at therapeutic doses, overdoses cause acute liver damage characterized by centrilobular hepatic necrosis. One of the major clinical problems of paracetamol-induced liver disease is the development of hemorrhagic alterations. Although hepatocytes represent the main target of the cytotoxic effect of paracetamol overdose, perturbations within the endothelium involving morphological changes of liver sinusoidal endothelial cells (LSECs) have also been described in paracetamol-induced liver disease. Recently, we have shown that paracetamol-induced liver damage is synergistically enhanced by the TRAIL signaling pathway. As LSECs are constantly exposed to activated immune cells expressing death ligands, including TRAIL, we investigated the effect of TRAIL on paracetamol-induced LSEC death. We here demonstrate for the first time that TRAIL strongly enhances paracetamol-mediated LSEC death with typical features of apoptosis. Inhibition of caspases using specific inhibitors resulted in a strong reduction of cell death. TRAIL appears to enhance paracetamol-induced LSEC death via the activation of the pro-apoptotic BH3-only proteins Bid and Bim, which initiate the mitochondrial apoptotic pathway. Taken together this study shows that the liver endothelial layer, mainly LSECs, represent a direct target of the cytotoxic effect of paracetamol and that activation of TRAIL receptor synergistically enhances paracetamol-induced LSEC death via the mitochondrial apoptotic pathway. TRAIL-mediated acceleration of paracetamol-induced cell death may thus contribute to the pathogenesis of paracetamol-induced liver damage.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

Badmann A,Langsch S,Keogh A,Brunner T,Kaufmann T,Corazza N

doi

10.1038/cddis.2012.185

subject

Has Abstract

pub_date

2012-12-20 00:00:00

pages

e447

issn

2041-4889

pii

cddis2012185

journal_volume

3

pub_type

杂志文章
  • 6-Phosphofructo-2-kinase (PFKFB3) promotes cell cycle progression and suppresses apoptosis via Cdk1-mediated phosphorylation of p27.

    abstract::The control of glucose metabolism and the cell cycle must be coordinated in order to guarantee sufficient ATP and anabolic substrates at distinct phases of the cell cycle. The family of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases (PFKFB1-4) are well established regulators of glucose metabolism via their synt...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2014.292

    authors: Yalcin A,Clem BF,Imbert-Fernandez Y,Ozcan SC,Peker S,O'Neal J,Klarer AC,Clem AL,Telang S,Chesney J

    更新日期:2014-07-17 00:00:00

  • MicroRNA-181a-5p and microRNA-181a-3p cooperatively restrict vascular inflammation and atherosclerosis.

    abstract::MicroRNAs have emerged as important post-transcriptional regulators of gene expression and are involved in diverse diseases and cellular process. Decreased expression of miR-181a has been observed in the patients with coronary artery disease, but its function and mechanism in atherogenesis is not clear. This study was...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1599-9

    authors: Su Y,Yuan J,Zhang F,Lei Q,Zhang T,Li K,Guo J,Hong Y,Bu G,Lv X,Liang S,Ou J,Zhou J,Luo B,Shang J

    更新日期:2019-05-07 00:00:00

  • The SGK3-triggered ubiquitin-proteasome degradation of podocalyxin (PC) and ezrin in podocytes was associated with the stability of the PC/ezrin complex.

    abstract::Podocyte damage is commonly accompanied by destabilization of the podocalyxin (PC)/ezrin complex. Serum- and glucocorticoid-inducible kinase 3 (SGK3) plays a role in the maintenance of podocyte function, but the details of this role are poorly understood. Herein we demonstrated that SGK3 and its downstream target prot...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-1161-1

    authors: Yuan YP,Zhao H,Peng LQ,Li ZF,Liu S,Yuan CY,Mwamunyi MJ,Pearce D,Yao LJ

    更新日期:2018-11-01 00:00:00

  • Correction: ERβ promotes Aβ degradation via the modulation of autophagy.

    abstract::Following the publication of this article, the authors realized there was an error in Figure 6H in which two versions of the figure appear.This does not impact the conclusions of the article. ...

    journal_title:Cell death & disease

    pub_type: 已发布勘误

    doi:10.1038/s41419-019-1867-8

    authors: Wei Y,Zhou J,Wu J,Huang J

    更新日期:2019-08-23 00:00:00

  • Ca2+-dependent recruitment of voltage-gated sodium channels underlies bilirubin-induced overexcitation and neurotoxicity.

    abstract::Neonatal jaundice is prevalent among newborns and can lead to severe neurological deficits, particularly sensorimotor dysfunction. Previous studies have shown that bilirubin (BIL) enhances the intrinsic excitability of central neurons and this can potentially contribute to their overexcitation, Ca2+ overload, and neur...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1979-1

    authors: Shi HS,Lai K,Yin XL,Liang M,Ye HB,Shi HB,Wang LY,Yin SK

    更新日期:2019-10-10 00:00:00

  • The role of oligodendrocyte precursor cells expressing the GPR17 receptor in brain remodeling after stroke.

    abstract::Following stroke-induced neuronal damage, quiescent oligodendrocyte precursors (OPCs) are activated to proliferate and later to differentiate to myelin-producing cells. GPR17, a receptor transiently expressed on early OPCs, has emerged as a target to implement stroke repair through stimulation of OPC maturation. Howev...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2017.256

    authors: Bonfanti E,Gelosa P,Fumagalli M,Dimou L,Viganò F,Tremoli E,Cimino M,Sironi L,Abbracchio MP

    更新日期:2017-06-08 00:00:00

  • Apoptosis and necrosis: two different outcomes of cigarette smoke condensate-induced endothelial cell death.

    abstract::Cigarette smoking is one of the most important and preventable risk factors for atherosclerosis. However, because of the complex composition of cigarette smoke, the detailed pathophysiological mechanisms are not fully understood. Based on controversial reports on the pro-atherogenic activity of cigarette smoke condens...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2012.162

    authors: Messner B,Frotschnig S,Steinacher-Nigisch A,Winter B,Eichmair E,Gebetsberger J,Schwaiger S,Ploner C,Laufer G,Bernhard D

    更新日期:2012-11-15 00:00:00

  • The PAX6-ZEB2 axis promotes metastasis and cisplatin resistance in non-small cell lung cancer through PI3K/AKT signaling.

    abstract::Paired-box 6 (PAX6) is an important transcription factor required for the function of human neuroectodermal epithelial tissues. Previous studies have suggested that it is also expressed in several types of tumors and has an oncogenic role. However, little is known about its role in non-small cell lung cancer (NSCLC). ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1591-4

    authors: Wu DM,Zhang T,Liu YB,Deng SH,Han R,Liu T,Li J,Xu Y

    更新日期:2019-04-25 00:00:00

  • TIGAR/AP-1 axis accelerates the division of Lgr5- reserve intestinal stem cells to reestablish intestinal architecture after lethal radiation.

    abstract::During radiologic or nuclear accidents, high-dose ionizing radiation (IR) can cause gastrointestinal syndrome (GIS), a deadly disorder that urgently needs effective therapy. Unfortunately, current treatments based on natural products and antioxidants have shown very limited effects in alleviating deadly GIS. Reserve i...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-2715-6

    authors: Chen F,Zhang Y,Hu S,Shi X,Wang Z,Deng Z,Lin L,Zhang J,Pan Y,Bai Y,Liu F,Zhang H,Shao C

    更新日期:2020-07-06 00:00:00

  • The p75 receptor mediates axon growth inhibition through an association with PIR-B.

    abstract::The Nogo receptor and paired immunoglobulin-like receptor B (PIR-B) are receptors for three myelin-derived axon-growth inhibitors, including myelin-associated glycoprotein (MAG). In this study, we report that the p75 receptor is required for the signal transduction of PIR-B, which interacted with p75 upon ligand bindi...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2011.85

    authors: Fujita Y,Takashima R,Endo S,Takai T,Yamashita T

    更新日期:2011-09-01 00:00:00

  • PGC-1α buffers ROS-mediated removal of mitochondria during myogenesis.

    abstract::Mitochondrial biogenesis and mitophagy are recognized as critical processes underlying mitochondrial homeostasis. However, the molecular pathway(s) coordinating the balance between these cellular programs is still poorly investigated. Here, we show an induction of the nuclear and mitochondrial peroxisome proliferator-...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2014.458

    authors: Baldelli S,Aquilano K,Ciriolo MR

    更新日期:2014-11-06 00:00:00

  • Cooperative role of RanBP9 and P73 in mitochondria-mediated apoptosis.

    abstract::Mitochondrial dysfunction and synaptic damage are critical early features of Alzheimer's disease (AD) associated with amyloid β (Aβ) and τ. We previously reported that the scaffolding protein RanBP9, which is overall increased in AD, simultaneously promotes Aβ generation and focal adhesion disruption by accelerating t...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2012.203

    authors: Liu T,Roh SE,Woo JA,Ryu H,Kang DE

    更新日期:2013-01-24 00:00:00

  • Akt inhibitor SC66 promotes cell sensitivity to cisplatin in chemoresistant ovarian cancer cells through inhibition of COL11A1 expression.

    abstract::We studied Akt inhibition using SC66 in a NOD-SCID xenograft mouse model and a panel of eight ovarian cancer cell lines. Elevated phospho-Akt levels in cancerous tissue were associated with short progression-free survival and overall survival. Cell sensitivity to SC66 was inversely correlated with phospho-Akt and COL1...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1555-8

    authors: Wu YH,Huang YF,Chen CC,Chou CY

    更新日期:2019-04-11 00:00:00

  • RIP1 protects melanoma cells from apoptosis induced by BRAF/MEK inhibitors.

    abstract::Many recent studies have uncovered the necessary role for the receptor-interacting protein kinase 1 (RIP1) in regulating apoptosis and necrosis that cells undergo in response to various cellular stresses. However, the functional significance of RIP1 in promoting cancer cells survival remains poorly understood. Here, w...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-0714-7

    authors: Lei FX,Jin L,Liu XY,Lai F,Yan XG,Farrelly M,Guo ST,Zhao XH,Zhang XD

    更新日期:2018-06-07 00:00:00

  • microRNA-874 suppresses tumor proliferation and metastasis in hepatocellular carcinoma by targeting the DOR/EGFR/ERK pathway.

    abstract::The δ opioid receptor (DOR) is involved in the regulation of malignant transformation and tumor progression of hepatocellular carcinoma (HCC). However, regulation of the DOR in HCC remains poorly defined. We found that miR-874 was identified as a negative regulator of the DOR, which is a direct and functional target o...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-017-0131-3

    authors: Zhang Y,Wei Y,Li X,Liang X,Wang L,Song J,Zhang X,Zhang C,Niu J,Zhang P,Ren Z,Tang B

    更新日期:2018-01-26 00:00:00

  • Resveratrol regulates mitochondrial reactive oxygen species homeostasis through Sirt3 signaling pathway in human vascular endothelial cells.

    abstract::Mitochondrial reactive oxygen species (mtROS) homeostasis plays an essential role in preventing oxidative injury in endothelial cells, an initial step in atherogenesis. Resveratrol (RSV) possesses a variety of cardioprotective activities, however, little is known regarding the effects of RSV on mtROS homeostasis in en...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2014.530

    authors: Zhou X,Chen M,Zeng X,Yang J,Deng H,Yi L,Mi MT

    更新日期:2014-12-18 00:00:00

  • Suppression of SUN2 by DNA methylation is associated with HSCs activation and hepatic fibrosis.

    abstract::Hepatic myofibroblasts, activated hepatic stellate cells (HSCs), are the main cell type of extracellular matrix (ECM) deposition during hepatic fibrosis. Aberrant DNA methylation-regulated HSCs activation in liver fibrogenesis has been reported, but the functional roles and mechanisms of DNA methylation in hepatic fib...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-1032-9

    authors: Chen X,Li WX,Chen Y,Li XF,Li HD,Huang HM,Bu FT,Pan XY,Yang Y,Huang C,Meng XM,Li J

    更新日期:2018-10-03 00:00:00

  • GATA3 recruits UTX for gene transcriptional activation to suppress metastasis of breast cancer.

    abstract::GATA3 has emerged as a prominent transcription factor required for maintaining mammary-gland homeostasis. GATA3 loss is associated with aggressive breast cancer development, but the mechanism by which breast cancer is affected by the loss of GATA3 function remains unclear. Here, we report that GATA3 expression is posi...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-2062-7

    authors: Yu W,Huang W,Yang Y,Qiu R,Zeng Y,Hou Y,Sun G,Shi H,Leng S,Feng D,Chen Y,Wang S,Teng X,Yu H,Wang Y

    更新日期:2019-11-04 00:00:00

  • DDX3 DEAD-box RNA helicase plays a central role in mitochondrial protein quality control in Leishmania.

    abstract::DDX3 is a highly conserved member of ATP-dependent DEAD-box RNA helicases with multiple functions in RNA metabolism and cellular signaling. Here, we describe a novel function for DDX3 in regulating the mitochondrial stress response in the parasitic protozoan Leishmania. We show that genetic inactivation of DDX3 leads ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2016.315

    authors: Padmanabhan PK,Zghidi-Abouzid O,Samant M,Dumas C,Aguiar BG,Estaquier J,Papadopoulou B

    更新日期:2016-10-13 00:00:00

  • CXCL12 inhibits expression of the NMDA receptor's NR2B subunit through a histone deacetylase-dependent pathway contributing to neuronal survival.

    abstract::Homeostatic chemokines, such as CXCL12, can affect neuronal activity by the regulation of inhibitory and excitatory neurotransmission, but the mechanisms involved are still undefined. Our previous studies have shown that CXCL12 protects cortical neurons from excitotoxicity by promoting the function of the gene-repress...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2010.10

    authors: Nicolai J,Burbassi S,Rubin J,Meucci O

    更新日期:2010-04-01 00:00:00

  • Control of glioma cell death and differentiation by PKM2-Oct4 interaction.

    abstract::Glioma stem cells are highly resistant to cell death and as such are supposed to contribute to tumor recurrence by eluding anticancer treatments. Here, we show that spheroids that contain rat neural stem cells (NSCs) or rat glioma stem cells (cancer stem cells, CSCs) express isoforms 1 and 2 of pyruvate kinase (PKM1 a...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2013.561

    authors: Morfouace M,Lalier L,Oliver L,Cheray M,Pecqueur C,Cartron PF,Vallette FM

    更新日期:2014-01-30 00:00:00

  • E2F1 mediated DDX11 transcriptional activation promotes hepatocellular carcinoma progression through PI3K/AKT/mTOR pathway.

    abstract::The DEAD/DEAH box helicase 11 (DDX11) plays vital roles in regulating the initiation of DNA replication. However, its precise function and regulation in hepatocellular carcinoma (HCC) have never been reported yet. In the current study, we found that DDX11 was overexpressed in HCC tissues. High DDX11 expression was pos...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-2478-0

    authors: Yu Y,Zhao D,Li K,Cai Y,Xu P,Li R,Li J,Chen X,Chen P,Cui G

    更新日期:2020-04-24 00:00:00

  • Serum amyloid A inhibits dendritic cell apoptosis to induce glucocorticoid resistance in CD4(+) T cells.

    abstract::Mediators produced by the airway epithelium control the activation, recruitment, and survival of pulmonary dendritic cells (DC) that present antigen to CD4(+) T cells during the genesis and exacerbation of allergic asthma. The epithelial-derived acute phase protein, serum amyloid A (SAA), induces DC maturation and TH1...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2013.327

    authors: Ather JL,Fortner KA,Budd RC,Anathy V,Poynter ME

    更新日期:2013-09-05 00:00:00

  • Cystathionine β-synthase (CBS) deficiency suppresses erythropoiesis by disrupting expression of heme biosynthetic enzymes and transporter.

    abstract::The reduced iron usage induced by the suppression of erythropoiesis is a major cause of the systemic iron overload in CBS knockout (CBS-/-) mice. However, the relevant mechanisms are unknown. Here, we examined changes in granulocyte/erythroid cell ratios, iron content, and expression of iron-metabolism proteins, inclu...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1951-0

    authors: Zhao P,Qian C,Chen YJ,Sheng Y,Ke Y,Qian ZM

    更新日期:2019-09-24 00:00:00

  • HOXA5 inhibits the proliferation and neoplasia of cervical cancer cells via downregulating the activity of the Wnt/β-catenin pathway and transactivating TP53.

    abstract::HOXA5 is considered a regulator involved in embryonic development and cellular differentiation and a tumor suppressor. Nevertheless, its biological role in cervical carcinoma is still unclear. In the present study, immunohistochemistry showed that HOXA5 expression gradually decreased as the degree of cervical lesions ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-2629-3

    authors: Ma HM,Cui N,Zheng PS

    更新日期:2020-06-04 00:00:00

  • Continuous exposure of pancreatic cancer cells to dietary bioactive agents does not induce drug resistance unlike chemotherapy.

    abstract::The repeated treatment of cancer cells with chemo- or radiotherapy induces therapy resistance, but it was previously unknown whether the same effect occurs upon continuous exposure of cancer cells to diet-derived chemopreventive agents. We elucidated this interesting question in pancreatic ductal adenocarcinoma, which...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2016.157

    authors: Fan P,Zhang Y,Liu L,Zhao Z,Yin Y,Xiao X,Bauer N,Gladkich J,Mattern J,Gao C,Schemmer P,Gross W,Herr I

    更新日期:2016-06-02 00:00:00

  • Human umbilical cord mesenchymal stem cell-derived extracellular vesicles promote lung adenocarcinoma growth by transferring miR-410.

    abstract::Although accumulating evidence has linked mesenchymal stem cells (MSCs) with tumor growth, the underlying mechanisms are poorly understood. Here, we demonstrated for the first time that human umbilical cord MSCs (hUCMSCs) dramatically increased the growth of lung adenocarcinoma (LUAD) cancer cells in a xenograft tumor...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-0323-5

    authors: Dong L,Pu Y,Zhang L,Qi Q,Xu L,Li W,Wei C,Wang X,Zhou S,Zhu J,Wang X,Liu F,Chen X,Su C

    更新日期:2018-02-13 00:00:00

  • The JAK2/STAT3 and mitochondrial pathways are essential for quercetin nanoliposome-induced C6 glioma cell death.

    abstract::The formulation of quercetin nanoliposomes (QUE-NLs) has been shown to enhance QUE antitumor activity in C6 glioma cells. At high concentrations, QUE-NLs induce necrotic cell death. In this study, we probed the molecular mechanisms of QUE-NL-induced C6 glioma cell death and examined whether QUE-NL-induced programmed c...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2013.242

    authors: Wang G,Wang JJ,Chen XL,Du SM,Li DS,Pei ZJ,Lan H,Wu LB

    更新日期:2013-08-01 00:00:00

  • Inhibition of AIM2 inflammasome-mediated pyroptosis by Andrographolide contributes to amelioration of radiation-induced lung inflammation and fibrosis.

    abstract::Radiation-induced lung injury (RILI) is one of the most common and fatal complications of thoracic radiotherapy, whereas no effective interventions are available. Andrographolide, an active component extracted from Andrographis paniculate, is prescribed as a treatment for upper respiratory tract infection. Here we rep...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-2195-8

    authors: Gao J,Peng S,Shan X,Deng G,Shen L,Sun J,Jiang C,Yang X,Chang Z,Sun X,Feng F,Kong L,Gu Y,Guo W,Xu Q,Sun Y

    更新日期:2019-12-20 00:00:00

  • The role of autophagy in asparaginase-induced immune suppression of macrophages.

    abstract::Erwinia asparaginase, a bacteria-derived enzyme drug, has been used in the treatment of various cancers, especially acute lymphoblastic leukemia (ALL). One of the most significant side effects associated with asparaginase administration is immune suppression, which limits its application in clinic. Macrophages are pha...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2017.144

    authors: Song P,Wang Z,Zhang X,Fan J,Li Y,Chen Q,Wang S,Liu P,Luan J,Ye L,Ju D

    更新日期:2017-03-30 00:00:00