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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

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

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

Activation of the aryl hydrocarbon receptor decreases rifampicin-induced CYP3A4 expression in primary human hepatocytes and HepaRG.
In conclusion, the presented results suggested that the cross-talk between PXR and AhR plays a role in the regulation of CYP3A4 gene expression. PMID: 28571685 [PubMed - as supplied by publisher]
Source: Toxicology Letters - May 29, 2017 Category: Toxicology Authors: Rasmussen MK, Daujat-Chavanieu M, Gerbal-Chaloin S Tags: Toxicol Lett Source Type: research

Silver nanoparticle-induced phosphorylation of histone H3 at serine 10 is due to dynamic changes in actin filaments and the activation of Aurora kinases.
Abstract The phosphorylation of histone H3 at serine 10 (p-H3S10) has been closely correlated with mitotic chromosome condensation. We previously reported that silver nanoparticles (AgNPs) significantly induced p-H3S10 independent of mitosis. In the present study, we examined the mechanisms underlying the induction of p-H3S10 by AgNPs. A treatment with AgNPs markedly induced p-H3S10 in a dose-dependent manner in three types of cell lines, and this was dependent on the cellular incorporation of AgNPs. The immunofluorescent staining of AgNP-induced p-H3S10 was thin and solid throughout the nucleus, and differed from...
Source: Toxicology Letters - May 9, 2017 Category: Toxicology Authors: Zhao X, Toyooka T, Ibuki Y Tags: Toxicol Lett Source Type: research

4-Nonylphenol induces autophagy and attenuates mTOR-p70S6K/4EBP1 signaling by modulating AMPK activation in Sertoli cells.
In this study we exposed 7-week-old male rats to NP by intra-peritoneal injection at 0, 20, 50 or 100mg/kg body weight/2days for 20 consecutive days. Our results showed that exposure to NP dose-dependently induces the formation of autophagosomes in SCs, increases the expression of Beclin-1, the conversion of LC3-I to LC3-II and the mRNA expression of Atg3, Atg5, Atg7 and Atg12 in testis, and these effects are concomitant with the activation of AMPK, and the suppression of TSC2-mTOR-p70S6K/4EBP1 signaling cascade in testis. Furthermore, 10μM Compound C or AMPKα1 siRNA pre-treatment effectively attenuated autophagy and rev...
Source: Toxicology Letters - December 28, 2016 Category: Toxicology Authors: Duan P, Hu C, Quan C, Yu T, Huang W, Chen W, Tang S, Shi Y, Martin FL, Yang K Tags: Toxicol Lett Source Type: research

Salvianolic acid B protects against chronic alcoholic liver injury via SIRT1-mediated inhibition of CRP and ChREBP in rats.
This study investigated the hepatoprotective effects of SalB in chronic alcoholic liver disease (ALD) and explored the related signaling mechanisms. In vivo, SalB treatment significantly attenuated ethanol-induced liver injury by blocking the elevation of serum aminotransferase activities and markedly decreased hepatic lipid accumulation by reducing serum and liver triglyceride (TG) and total cholesterol (TC) levels. Moreover, SalB treatment ameliorated ethanol-induced hepatic inflammation by decreasing the levels of hepatotoxic cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Importantly, SalB...
Source: Toxicology Letters - December 14, 2016 Category: Toxicology Authors: Zhang N, Hu Y, Ding C, Zeng W, Shan W, Fan H, Zhao Y, Shi X, Gao L, Xu T, Wang R, Gao D, Yao J Tags: Toxicol Lett Source Type: research

Combined treatment with vitamin C and sulindac synergistically induces p53- and ROS-dependent apoptosis in human colon cancer cells.
In this study, we evaluated a combinatorial strategy utilizing sulindac and vitamin C. The death of HCT116 cells upon combination therapy occurred via a p53-mediated mechanism. The combination therapeutic resistance developed in isogenic p53 null HCT116 cells and siRNA-mediated p53 knockdown HCT116 cells, but the exogenous expression of p53 in p53 null isogenic cells resulted in the induction of cell death. In addition, we investigated an increased level of intracellular ROS (reactive oxygen species), which was preceded by p53 activation. The expression level of PUMA (p53-upregulated modulator of apoptosis), but not Bim, w...
Source: Toxicology Letters - June 19, 2016 Category: Toxicology Authors: Gong EY, Shin YJ, Hwang IY, Kim JH, Kim SM, Moon JH, Shin JS, Lee DH, Hur DY, Jin DH, Hong SW, Lee WK, Lee WJ Tags: Toxicol Lett Source Type: research

Role of PUMA in methamphetamine-induced neuronal apoptosis.
This study aimed to examine the effects of PUMA in METH-induced neuronal apoptosis. We determined PUMA protein expression in PC12 cells and SH-SY5Y cells after METH exposure using western blot. We also observed the effect of METH on neuronal apoptosis after silencing PUMA expression with siRNA using TUNEL staining and flow cytometry. Additionally, to investigate possible mechanisms of METH-induced PUMA-mediated neuronal apoptosis, we measured the protein expression of apoptotic markers, including cleaved caspase-3, cleaved PARP, Bax, B-cell leukemia/lymphoma-2 (Bcl-2) and cytochrome c (cyto c), after METH treatment with or...
Source: Toxicology Letters - October 30, 2015 Category: Toxicology Authors: Chen C, Qincao L, Xu J, Du S, Huang E, Liu C, Lin Z, Xie WB, Wang H Tags: Toxicol Lett Source Type: research

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