Abstract:
:Cholestasis represents pathophysiologic syndromes defined as impaired bile flow from the liver. As an outcome, bile acids accumulate and promote hepatocyte injury, followed by liver cirrhosis and liver failure. Glycochenodeoxycholic acid (GCDCA) is relatively toxic and highly concentrated in bile and serum after cholestasis. However, the mechanism underlying GCDCA-induced hepatotoxicity remains unclear. In this study, we found that GCDCA inhibits autophagosome formation and impairs lysosomal function by inhibiting lysosomal proteolysis and increasing lysosomal pH, contributing to defects in autophagic clearance and subsequently leading to the death of L02 human hepatocyte cells. Notably, through tandem mass tag (TMT)-based quantitative proteomic analysis and database searches, 313 differentially expressed proteins were identified, of which 71 were increased and 242 were decreased in the GCDCA group compared with those in the control group. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that GCDCA suppressed the signaling pathway of transcription factor E3 (TFE3), which was the most closely associated with autophagic flux impairment. In contrast, GCDCA-inhibited lysosomal function and autophagic flux were efficiently attenuated by TFE3 overexpression. Specifically, the decreased expression of TFE3 was closely related to the disruption of reactive oxygen species (ROS) homeostasis, which could be prevented by inhibiting intracellular ROS with N-acetyl cysteine (NAC). In summary, our study is the first to demonstrate that manipulation of ROS/TFE3 signaling may be a therapeutic approach for antagonizing GCDCA-induced hepatotoxicity.
journal_name
Toxicol Lettjournal_title
Toxicology lettersauthors
Lan W,Chen Z,Chen Y,Tan M,Chen Y,Chen J,Chi X,Chen Ydoi
10.1016/j.toxlet.2020.05.017subject
Has Abstractpub_date
2020-10-01 00:00:00pages
11-21eissn
0378-4274issn
1879-3169pii
S0378-4274(20)30156-9journal_volume
331pub_type
杂志文章abstract::Stoichiometric conversion of methyl acetate to methanol in vitro was detected when methyl acetate was incubated with blood for 2 to 8 h. The velocity of the reaction was so fast that almost all of methyl acetate disappeared in 8 h. The methanol formation was further confirmed by means of gas-chromatography-mass spectr...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(92)90028-i
更新日期:1992-09-01 00:00:00
abstract::In the olfactory epithelium the primary olfactory neurons are in contact with the environment in the nasal cavity and they are also connected to the olfactory bulbs of the brain. These neurons may therefore provide a pathway by which foreign materials may reach the brain. Inhalation of cobalt-containing dust or fumes ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/s0378-4274(03)00266-2
更新日期:2003-11-01 00:00:00
abstract::Carbon nanotubes (CNT), despite their diverse application potential, have demonstrated adverse impacts in vitro and in vivo. Previous studies have focused on the combined in vitro cytotoxic impact of CNT aggregates and associated nanoparticulate impurities. However, the isolated effect of CNT aggregates and associated...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2006.12.003
更新日期:2007-02-28 00:00:00
abstract::Allyl alcohol-induced LDH leakage from isolated rat hepatocytes was preceded by a decrease in rhodmine 123 retention, signifying a loss of mitochondrial membrane potential. Addition of dithiothreitol (DTT) prevented the drop in membrane potential and completely prevented cell killing by allyl alcohol. In contrast, cyc...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(95)03426-9
更新日期:1995-11-15 00:00:00
abstract::Cellular senescence is characterized by irreversible cell arrest and is associated with the development of chronic diseases, including cancer. Here, we investigated the induction of cellular senescence during liver carcinogenesis. Liver cancer was induced in Fischer 344 rats with a weekly intraperitoneal injection of ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2015.11.011
更新日期:2016-01-22 00:00:00
abstract::The NLRP3 inflammasome, composed of caspase-1, NLRP3 and ASC, plays a critical role in the clearance of microbial pathogens. Here, we found that the treatment of mouse macrophages with the zinc-containing dithiocarbamate ziram, a widely used fungicide in agriculture, caused a decrease in pro-caspase-1 and NLRP3 levels...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2015.04.012
更新日期:2015-06-15 00:00:00
abstract::3-Bromopyruvate (3-BrPA) is a promising agent that has been widely studied in the treatment of cancer and pulmonary hypertension. Rotenone is a pesticide commonly used on farms and was shown to have anti-cancer activity and delay fibrosis progression in chronic kidney disease in a recent study. However, there are few ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2019.09.024
更新日期:2020-01-01 00:00:00
abstract::Between 1997 and 2011, more than 200 new substances were notified through the early-warning system, with the record number of 49 novel molecules reported in 2011. The pattern of acute toxicity associated with the consumption of these new substances is generally similar to that seen with traditional drugs of abuse. Rec...
journal_title:Toxicology letters
pub_type: 杂志文章,评审
doi:10.1016/j.toxlet.2012.04.019
更新日期:2012-07-07 00:00:00
abstract::The objective of this research was to develop a mathematical description of uptake of aromatic and aliphatic hydrocarbons into the stratum corneum of human skin in vivo. A simple description based on Fick's laws of diffusion was used to predict the spatiotemporal variation of naphthalene, 1- and 2-methylnaphthalene, u...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2008.03.005
更新日期:2008-05-30 00:00:00
abstract::Using equimolar quantities of 2 chemical allergens, toluene diisocyanate (TDI), noted for its ability to cause respiratory hypersensitivity, and dinitrochlorobenzene (DNCB), noted for its dermal sensitizing activity, the mouse was evaluated as a possible model to indicate respiratory hypersensitivity. A previously pub...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(94)03234-x
更新日期:1995-06-01 00:00:00
abstract::The biomedical application of single-walled carbon nanotubes (SWCNTs), such as drug delivery and cancer treatment, requires a clear understanding of their fate and toxicological profile after intravenous administration. In this study, the long-term accumulation and toxicity of intravenously injected SWCNTs in the main...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2008.07.020
更新日期:2008-10-01 00:00:00
abstract::Interstitial pulmonary fibrosis is characterized by an abnormal accumulation of fibroblasts with a resultant increase in lung collagen content. Previous research has implied a possible involvement of the T-lymphocyte in this process. We used cyclosporin A (Cy A), a known immunosuppressant, to deplete T-lymphocyte-depe...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(85)90162-6
更新日期:1985-08-01 00:00:00
abstract::The early histologic lesions and sequential changes in the development of mirex-induced cataracts were studied in the offspring of lactating female Sherman rats given oral doses of mirex for 5 consecutive days post partum. The earliest histologic change, seen at neonatal day 7, was slight swelling of the individual co...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(81)90163-6
更新日期:1981-11-01 00:00:00
abstract::This paper reviews the results from past regulatory and mechanistic inhalation studies in rats with the type II pyrethroid Cyfluthrin. Apart from many chemical irritants, Cyfluthrin was shown to be a neuroexcitatory agent without any inherent tissue-destructive or irritant property. Thus, any Cyfluthrin-induced neuroe...
journal_title:Toxicology letters
pub_type: 杂志文章,评审
doi:10.1016/j.toxlet.2017.10.003
更新日期:2018-01-05 00:00:00
abstract::Cadmium (Cd), is a well-known environmental and occupational hazard with a potent neurotoxic action. However, the mechanism underlying cadmium-induced neurotoxicity remains unclear. Herein, we exposed Neuro-2a cells to different concentrations of cadmium chloride (CdCl2) (12.5, 25 and 50 μM) for 24 h and found that Cd...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2018.07.015
更新日期:2018-10-01 00:00:00
abstract::The molecular basis of the interindividual differences of normal individuals to ionizing radiation is poorly understood. Several studies in telomerase KO mice with short telomeres have uncovered an inverse relationship between telomere length and radiation sensitivity. The present work aims to determine if chromosome ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2007.05.012
更新日期:2007-07-30 00:00:00
abstract::An atomic absorption spectrophotometric (AAS) method was successfully applied to analysis of urine for arsenic (As) as a measure of biological monitoring of occupational exposure to As in Vietnam. The application of the method to urine samples from 75 non-exposed control urbanites (after 2-day abstinence from sea food...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/s0378-4274(99)00087-9
更新日期:1999-09-05 00:00:00
abstract::Tetrachloro-p-hydroquinone (TCHQ), the major metabolite of pentachlorophenol (PCP) in mammalian systems, is known to autoxidize to its semiquinone radical under physiological conditions. In this way, PCP could present a potent source of reactive oxygen species (ROS) during metabolization. ROS contribute to numerous mo...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(94)90085-x
更新日期:1994-12-01 00:00:00
abstract::Little information is available upon the effects of carbon nanotubes (CNT) on the airway barrier. Here we study the barrier function of Calu-3 human airway epithelial cells, grown on permeable filters, after the exposure to commercial single-walled or multi-walled CNT, produced through chemical vapour deposition. To a...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2008.02.007
更新日期:2008-05-05 00:00:00
abstract::This study involved an attempt to establish a new photosafety screening system for dermally-applied chemicals consisting of a reactive oxygen species (ROS) assay and an in vitro skin permeation test. The ROS assay was undertaken to evaluate photoreactivity of six test compounds, acridine (ACD), furosemide (FSM), hexac...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2019.09.016
更新日期:2019-12-15 00:00:00
abstract::Sulfolane is a solvent which produces hypothermia and decreased oxygen consumption following acute exposure. In the present experiment, we investigated effects of sulfolane on a behavioral measure of toxicity at ambient temperatures which would either prevent or facilitate the development of hypothermia. Adult male Lo...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(85)90018-9
更新日期:1985-11-01 00:00:00
abstract::Chronic exposure of humans to fluorine compounds in the air, water and food may be atherogenic via the activation of oxidative stress and increased ROS production. The most important factor that promotes the formation of ROS seems to be the oxidoreduction of electron carriers in the critical points of the respiratory ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2010.03.1167
更新日期:2010-07-01 00:00:00
abstract::Cultured Chinese hamster ovary (CHO) cells were incubated with dilutions of natural or synthetic crude oils and subsequently exposed to near ultraviolet light (NUV). Although the magnitude of photo-induced cytotoxicity in CHO was essentially independent of the source of the oil (within a factor of two), two shale oils...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(82)90205-3
更新日期:1982-10-01 00:00:00
abstract::288 BALB/c male mice were allocated to: Group 1-control; Group 2-500 ppm of 2-acetylaminofluorene (2-AAF) in the food, with control water; Group 4-500 ppm of 2-AAF in the food and 250 mg/100 ml of vitamin C in the water; and Group 3-control food and 250 mg% of vitamin C in the water. Major histopathologic changes at t...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(80)90136-8
更新日期:1980-09-01 00:00:00
abstract::1. The oocyte of the African clawed toad (Xenopus laevis) offers a reliable, sensitive and disease resistant system to investigate recombinantly and endogenously expressed Ca2+ signaling G protein-coupled receptors and their intracellular signaling pathways. 2. To study receptor induced Ca2+ release, two-electrode vol...
journal_title:Toxicology letters
pub_type: 杂志文章,评审
doi:10.1016/s0378-4274(98)00201-x
更新日期:1998-11-23 00:00:00
abstract::Effect of 120 days of continuous exposure of three sublethal concentrations (1/2, 1/4 and 1/8 fractions of 96 h LC50) of Basalin on alkaline phosphatase (Alk P), acid phosphatase (Acid P), lactic dehydrogenase (LDH), succinic dehydrogenase (SDH), glutamic oxaloacetic transaminase (GOT), and glutamic pyruvic transamina...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(83)90184-4
更新日期:1983-05-01 00:00:00
abstract::Increasing evidences suggest that microcystins, a kind of toxic metabolites, produced by cyanobacteria in contaminated water may contribute to the aggravation of the human colorectal carcinoma. Our previous study showed that microcystin-LR (MC-LR) exposure caused significant invasion and migration of colorectal cancer...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2016.11.004
更新日期:2017-01-04 00:00:00
abstract::Exposure to airborne particulate matter (PM) is a major risk factor for allergic airway inflammation such as asthma. Many of the PM components (i.e., polycyclic aromatic hydrocarbons and metals) are redox-active and capable of inducing cellular oxidative stress and injuries including inflammation and cell death. Airwa...
journal_title:Toxicology letters
pub_type: 杂志文章,评审
doi:10.1016/j.toxlet.2015.05.017
更新日期:2015-08-19 00:00:00
abstract::A study has been made of the effect of cadmium chloride and zinc acetate on the adherence of Streptococcus faecalis, Escherichia coli and Candida albicans to buccal cells from man. Cadmium led to a significant decrease in the adherence of the three microorganisms tested. Zinc increased the adherence of S. faecalis and...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(83)90207-2
更新日期:1983-02-01 00:00:00
abstract::Grain should be harvested at lowest possible humidity, or immediately dried to safe storage humidity to prevent the growth of fungi. Critical steps of grain harvest like conditions of used combine harvester, temperatures and aeration are discussed on their impact on mycotoxin formation. ...
journal_title:Toxicology letters
pub_type: 杂志文章,评审
doi:10.1016/j.toxlet.2004.04.043
更新日期:2004-10-10 00:00:00