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High mobility group box-1 protects against Aflatoxin G1-induced pulmonary epithelial cell damage in the lung inflammatory environment.
Abstract Aflatoxin G1 (AFG1) is a member of the carcinogenic aflatoxin family. Our previous studies indicated that oral administration of AFG1 caused tumor necrosis factor (TNF)-〈-dependent inflammation that enhanced oxidative DNA damage in alveolar epithelial cells, which may be related to AFG1-induced lung carcinogenesis. High mobility group box-1 (HMGB1) is a nuclear DNA-binding protein; the intracellular and extracellular roles of HMGB1 have been shown to contribute to DNA repair and sterile inflammation. The role of HMGB1 in DNA damage in an aflatoxin-induced lung inflammatory environment was investigated i...
Source: Toxicology Letters - May 20, 2020 Category: Toxicology Authors: Kang L, Guo N, Liu X, Wang X, Guo W, Xie SM, Liu C, Lv P, Xing L, Zhang X, Shen H Tags: Toxicol Lett Source Type: research

Decrease in ADAR1 expression by exposure to cigarette smoke enhances susceptibility to oxidative stress.
In conclusion, we show that ADAR1 expression is decreased by cigarette smoking and is a factor that contributes to the enhanced intracellular oxidative stress caused by cigarette smoking. PMID: 32439581 [PubMed - as supplied by publisher]
Source: Toxicology Letters - May 17, 2020 Category: Toxicology Authors: Takizawa M, Nakano M, Fukami T, Nakajima M Tags: Toxicol Lett Source Type: research

NIX compensates lost role of Parkin in Cd-induced mitophagy in HeLa cells through phosphorylation.
Abstract Our previous study demonstrated that cadmium (Cd) is an effective inducer of mitophagy, which is mainly mediated by PINK1/Parkin pathway. However, the role of other mitophagy pathways in Cd-induced mitophagy remains elusive. The present study employed HeLa cells, lacking fully functional Parkin, as a cell model to study Parkin-independent mitophagy pathway induced by Cd. Our results showed that BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (Bnip3L/NIX), an outer mitochondrial membrane mitophagy receptor, could provide an alternate pathway for Cd-induced mitophagy in HeLa cells. Specifica...
Source: Toxicology Letters - March 2, 2020 Category: Toxicology Authors: Naeem S, Qi Y, Tian Y, Zhang Y Tags: Toxicol Lett Source Type: research

Involvement of aryl hydrocarbon receptor in the cytotoxicity of corannulene and its derivatives.
Abstract Despite numerous studies on the toxicities of planar polycyclic aromatic hydrocarbons (PAHs), very little is known about the toxicological profiles of non-planar PAHs. In the present study, the cytotoxicity of corannulene (COR), a typical bowl-shaped PAH with a myriad of applications in the area of material chemistry, and benzo[a]pyrene (BaP), a typical planar PAH with similar molecular weight, were systematically compared in various cell lines. Compared with BaP, exposure to COR resulted in less cytotoxic responses in both human (HepG2) and murine (Hepa1-6) hepatoma cells, which was characterized with a ...
Source: Toxicology Letters - December 8, 2019 Category: Toxicology Authors: Li G, Ma R, Xing Y, Wei J, Bi Y, Li C, Xiong H, Baldridge KK, Huang J, Siegel JS, Zhang Y Tags: Toxicol Lett Source Type: research

Annexin A3 may play an important role in ochratoxin-induced malignant transformation of human gastric epithelium cells.
Abstract Ochratoxin A (OTA), one of the most abundant food-contaminating mycotoxins, is a possible carcinogen to humans. We previously demonstrated that long-term (40 weeks) OTA exposure induces the malignant transformation of human gastric epithelium cells (GES-1) in vitro. However, the specific mechanism underlying OTA-induced gastric carcinogenesis is complex. In the present study, we used 2-DE and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI/TOF MS) combined with bioinformatics and immunoblotting to investigate the differentially expressed proteins between GES-1 and OTA-m...
Source: Toxicology Letters - July 1, 2019 Category: Toxicology Authors: Wang J, Jia X, Meng X, Li Y, Wu W, Zhang X, Xu H, Cui J Tags: Toxicol Lett Source Type: research

Involvement of C/EBP β-related signaling pathway in methamphetamine-induced neuronal autophagy and apoptosis.
Involvement of C/EBPβ-related signaling pathway in methamphetamine-induced neuronal autophagy and apoptosis. Toxicol Lett. 2019 May 03;: Authors: Huang E, Huang H, Guan T, Liu C, Qu D, Xu Y, Yang J, Yan L, Xiong Y, Liang T, Wang Q, Chen L Abstract Methamphetamine (METH) is a widely abused illicit psychoactive drug. Our previous study has shown that CCAAT-enhancer binding protein β (C/EBPβ) is an important regulator in METH-induced neuronal autophagy and apoptosis. However, the detailed molecular mechanisms underlying this process remain poorly understood. Previous studies have demonstrated that DNA...
Source: Toxicology Letters - May 2, 2019 Category: Toxicology Authors: Huang E, Huang H, Guan T, Liu C, Qu D, Xu Y, Yang J, Yan L, Xiong Y, Liang T, Wang Q, Chen L Tags: Toxicol Lett Source Type: research

Transient Receptor Potential Melastatin 4 Contributes to Early-Stage Endothelial Injury Induced by Arsenic Trioxide.
CONCLUSION: TRPM4 is involved in endothelial injury induced by ATO and may be a promising therapeutic target for endothelial injury. PMID: 31054354 [PubMed - as supplied by publisher]
Source: Toxicology Letters - April 30, 2019 Category: Toxicology Authors: Yu CX, Zhang YY, Wu XY, Tang HX, Liang XQ, Xue ZM, Xue YD, Li J, Zhu H, Huo R, Ban T Tags: Toxicol Lett Source Type: research

CDK5-mediated Tau Accumulation Triggers Methamphetamine-induced Neuronal Apoptosis via Endoplasmic Reticulum-Associated Degradation Pathway.
Abstract Overexposure to methamphetamine (METH) causes apoptosis in a number of cell types, particularly neuronal cells. However, the underlying mechanisms of METH-induced neuronal apoptosis remain to be elucidated. Accumulation of microtubule-associated protein Tau can lead to activation of multiple neurotoxic pathways, which is closely correlated with neuronal apoptosis. The aim of this study was to determine the role of Tau in METH-induced neuronal apoptosis. We determined the expression of two phosphorylated Tau proteins (serine 396 and threonine 231) in the human neuroblastoma SH-SY5Y cells and in the hippoca...
Source: Toxicology Letters - April 26, 2018 Category: Toxicology Authors: Xiao N, Zhang F, Zhu B, Liu C, Lin Z, Wang H, Xie WB Tags: Toxicol Lett Source Type: research

Lead (Pb) induced ATM-dependent mitophagy via PINK1/Parkin pathway.
In this study, we found that Pb could trigger mitophagy in both HEK293 cells and the kidney cortex of male Kunming mice. However, whether ataxia telangiectasis mutated (ATM) which is reported to be linked with PTEN-induced putative kinase 1 (PINK1)/Parkin pathway (a well-characterized mitophagic pathway) participates in the regulation of Pb-induced mitophagy and its exact role remains enigmatic. Our results indicated that Pb activated ATM in vitro and in vivo, and further in vitro studies showed that ATM could co-localize with PINK1 and Parkin in cytosol and interact with PINK1. Knockdown of ATM by siRNA blocked Pb-induced...
Source: Toxicology Letters - April 13, 2018 Category: Toxicology Authors: Gu X, Qi Y, Feng Z, Ma L, Gao K, Zhang Y Tags: Toxicol Lett Source Type: research

Low Dose Cadmium Upregulates the Expression of von Willebrand Factor in Endothelial Cells.
In this study, we observed that low dose Cd treatment induced von Willebrand factor (vWF) expression in vascular endothelial cells in mouse lung and kidney tissues. In vitro analysis showed that 1 μM Cd specifically upregulated vWF mRNA and protein expression in human umbilical vein endothelial cells (HUVECs), indicating that Cd targets vascular endothelial cells even at relatively low concentrations. Further study demonstrated that nuclear factor kappa B (NF-κB) and GATA3, two established transcription regulators of the vWF gene, were not altered in the presence of Cd. However, ETS-related gene (ERG) was significantly...
Source: Toxicology Letters - March 20, 2018 Category: Toxicology Authors: Wang X, Dong F, Wang F, Yan S, Chen X, Tozawa H, Ushijima T, Kapron CM, Wada Y, Liu J Tags: Toxicol Lett Source Type: research

Involvement of HIF-1 α-regulated miR-21, acting via the Akt/NF-κB pathway, in malignant transformation of HBE cells induced by cigarette smoke extract.
Involvement of HIF-1α-regulated miR-21, acting via the Akt/NF-κB pathway, in malignant transformation of HBE cells induced by cigarette smoke extract. Toxicol Lett. 2018 Feb 28;: Authors: Lu L, Xu H, Yang P, Xue J, Chen C, Sun Q, Yang Q, Lu J, Shi A, Liu Q Abstract Although the relationship between cigarette smoke and lung cancer has been widely studied, the molecular mechanism for cigarette smoke-induced lung cancer remains largely unclear. The present study investigated the roles of hypoxia-inducible factor (HIF)-1α and miR-21 in the malignant transformation of human bronchial epithelial (HBE) ce...
Source: Toxicology Letters - February 28, 2018 Category: Toxicology Authors: Lu L, Xu H, Yang P, Xue J, Chen C, Sun Q, Yang Q, Lu J, Shi A, Liu Q Tags: Toxicol Lett Source Type: research

Acrylamide-induced oxidative stress and inflammatory response are alleviated by N-acetylcysteine in PC12 cells: Involvement of the crosstalk between Nrf2 and NF- κB pathways regulated by MAPKs.
This study focused on clarifying the crosstalk between the involved signaling pathways in ACR-induced oxidative stress and inflammatory response and investigating the protective effect of antioxidant N-acetylcysteine (NAC) against ACR in PC12 cells. Results revealed that ACR exposure led to oxidative stress characterized by significant increase in reactive oxygen species (ROS) and malondialdehyde (MDA) levels and glutathione (GSH) consumption. Inflammatory response was observed based on the dose-dependently increased levels of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6). NAC attenu...
Source: Toxicology Letters - February 6, 2018 Category: Toxicology Authors: Pan X, Wu X, Yan D, Peng C, Rao C, Yan H Tags: Toxicol Lett Source Type: research

ATF3 is positively involved in particulate matter-induced airway inflammation in vitro and in vivo.
Abstract Airborne particulate matter (PM) has been reported to be associated with a wide range of respiratory disorders. However, the mechanisms underlying PM-induced airway inflammation remain largely unknown. Generally, ATF3 negatively regulates pro-inflammatory cytokines production in response to TLR4 signaling. Here we first showed ATF3 has promoting effects in PM-induced airway inflammation in vitro an in vivo. We demonstrated PM significantly upregulated ATF3 expression in HBE cells and in mouse lung tissues. ATF3 siRNA markedly inhibited, while ATF3-recombinant over-expression plasmid significantly increase...
Source: Toxicology Letters - January 26, 2018 Category: Toxicology Authors: Yan F, Wu Y, Liu H, Wu Y, Shen H, Li W Tags: Toxicol Lett Source Type: research

ULK1-Regulated Autophagy: A Mechanism in Cellular Protection for ALDH2 against Hyperglycemia.
This study was designed to examine the mechanism behind ALDH2-offered protection against high glucose exposure with a focus on autophagy. H9C2 cells were cultured with normal or high glucose medium in the presence or absence of the ALDH2 agonist Alda-1. GFP-LC3 puncta and immunofluorescence were employed to assess autophagosome formation. Western blotting was applied to evaluate autophagy protein markers Atg5, LC3, p62, ULK1 phosphorylation and ALDH2. JC-1 staining was used to monitor mitochondrial membrane potential and mitochondrial injury. CCK-8 and TUNEL assays were employed for apoptosis and cell viability. Our result...
Source: Toxicology Letters - November 8, 2017 Category: Toxicology Authors: Liu M, Lu S, He W, Zhang L, Ma Y, Lv P, Ma M, Yu W, Wang J, Zhang M, Zhang Y, Li Y Tags: Toxicol Lett Source Type: research

MiR-34a/sirtuin-1/foxo3a is involved in genistein protecting against ox-LDL-induced oxidative damage in HUVECs.
In this study, human umbilical vein endothelial cells (HUVECs) were pretreated with genistein at different concentrations (10nM, 100nM and 1000nM) for 6h and then exposed to ox-LDL (50mg/L) for another 24h. Results showed that genistein restrained reactive oxygen species (ROS) and malondialdehyde (MDA) production, and ameliorated the inhibitory effect on superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and glutathione peroxidase (GPx) activity elicited by ox-LDL stimulation. The effects of genistein were correlated with the upregulation of sirtuin-1 via inhibiting miR-34a, and were abolished by sirtuin-1 siRNA...
Source: Toxicology Letters - July 5, 2017 Category: Toxicology Authors: Zhang H, Zhao Z, Pang X, Yang J, Yu H, Zhang Y, Zhou H, Zhao J Tags: Toxicol Lett Source Type: research

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