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Source: Toxicology Letters

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Total 86 results found since Jan 2013.

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

Zinc deficiency exacerbates while zinc supplement attenuates cardiac hypertrophy in high-fat diet-induced obese mice through modulating p38 MAPK-dependent signaling.
Abstract Childhood obesity often leads to cardiovascular diseases, such as obesity-related cardiac hypertrophy (ORCH), in adulthood, due to chronic cardiac inflammation. Zinc is structurally and functionally essential for many transcription factors; however, its role in ORCH and underlying mechanism(s) remain unclear and were explored here in mice with obesity induced with high-fat diet (HFD). Four week old mice were fed on either HFD (60%kcal fat) or normal diet (ND, 10% kcal fat) for 3 or 6 months, respectively. Either diet contained one of three different zinc quantities: deficiency (ZD, 10mg zinc per 4057kcal)...
Source: Toxicology Letters - June 20, 2016 Category: Toxicology Authors: Wang S, Luo M, Zhang Z, Gu J, Chen J, Payne KM, Tan Y, Wang Y, Yin X, Zhang X, Liu GC, Wintergerst K, Liu Q, Zheng Y, Cai L 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

Epigenetic silencing of p21 by long non-coding RNA HOTAIR is involved in the cell cycle disorder induced by cigarette smoke extract.
Abstract Long noncoding RNAs (lncRNAs), which are epigenetic regulators, are involved in human malignancies. Little is known, however, about the molecular mechanisms for lncRNA regulation of genes induced by cigarette smoke. We recently found that, in human bronchial epithelial (HBE) cells, the lncRNA, Hox transcript antisense intergenic RNA (HOTAIR), is associated with changes in the cell cycle caused by cigarette smoke extract (CSE). In the present study, we report that increased expression of HOTAIR and enhancer of zeste homolog 2 (EZH2), and tri-methylation of Lys 27 of histone H3 (H3K27me3), affect cell cycle...
Source: Toxicology Letters - October 23, 2015 Category: Toxicology Authors: Liu Y, Wang B, Liu X, Lu L, Luo F, Lu X, Shi L, Xu W, Liu Q Tags: Toxicol Lett Source Type: research

Immunochemical analysis of poly(ADP-ribosyl)ation in HaCaT keratinocytes induced by the mono-alkylating agent 2-chloroethyl ethyl sulfide (CEES): impact of experimental conditions.
In conclusion, this study provides a detailed analysis of the CEES-induced PARylation response in HaCaT keratinocytes, which forms an experimental basis to study the molecular mechanism of PARP1 activation and its functional consequences after mustard treatment in general. Such a study is presented in an accompanying article (Mangerich/Debiak/Birtel et al., this issue). PMID: 26383632 [PubMed - as supplied by publisher]
Source: Toxicology Letters - September 14, 2015 Category: Toxicology Authors: Debiak M, Lex K, Ponath V, Burckhardt-Boer W, Thiermann H, Steinritz D, Schmidt A, Mangerich A, Bürkle A Tags: Toxicol Lett Source Type: research

Comparison of human Nrf2 antibodies: A tale of two proteins.
Abstract The Nrf2 transcription factor is a master regulator of the cellular defense against oxidative and electrophilic stress. An increase in Nrf2 protein levels and an accumulation of Nrf2 in the nucleus are key parts of the Nrf2 activation mechanism. The western blot technique remains the most widely used method to assess these changes. A well-characterized, specific antibody that is commercially available would greatly enhance these studies in the field. Here, an apparently highly specific Nrf2 monoclonal antibody, EP1808Y from Abcam, is compared with the most widely used Nrf2 antibodies, H-300 and C-20, both...
Source: Toxicology Letters - July 25, 2015 Category: Toxicology Authors: Kemmerer ZA, Ader NR, Mulroy S, Eggler AL Tags: Toxicol Lett Source Type: research

Cytokine responses induced by diesel exhaust particles are suppressed by PAR-2 silencing and antioxidant treatment, and driven by polar and non-polar soluble constituents.
Abstract Adsorbed soluble organics seem to be the main drivers of inflammatory responses induced by diesel exhaust particles (DEP). The specific compounds contributing to this process and the cellular mechanisms behind DEP-induced inflammation are not well known. We have assessed pro-inflammatory effects of DEP and various soluble DEP fractions, in human bronchial epithelial cells (BEAS-2B). DEP increased the expression of interleukin (IL)-6 and CXCL8. Silencing of the aryl hydrocarbon receptor (AhR) by siRNA or pretreatment with AhR-antagonists did not attenuate DEP-induced IL-6 and CXCL8 responses. However, the ...
Source: Toxicology Letters - July 6, 2015 Category: Toxicology Authors: Bach N, Bølling AK, Brinchmann BC, Totlandsdal AI, Skuland T, Holme JA, Låg M, Schwarze PE, Øvrevik J Tags: Toxicol Lett Source Type: research

The IL-6/STAT3 pathway via miR-21 is involved in the neoplastic and metastatic properties of arsenite-transformed human keratinocytes.
Abstract Inflammation and microRNAs are involved in human skin cancer; however, their molecular mechanisms remain unclear. Further, a concern in skin cancer research is the identification of biomarkers for early diagnosis and accurate prognosis. To explore new biomarkers of chemical exposure in risk assessment of chemical carcinogenesis and arsenite-induced skin cancer, we investigated the roles of interleukin-6 (IL-6) regulation of microRNA-21 (miR-21), functioning via activation of signal transducers and activators of transcription 3 (STAT3), in neoplastic and metastatic properties of immortalized human keratino...
Source: Toxicology Letters - June 20, 2015 Category: Toxicology Authors: Lu X, Luo F, Liu Y, Zhang A, Li J, Wang B, Xu W, Shi L, Liu X, Lu L, Liu Q Tags: Toxicol Lett Source Type: research

GAPDH-knockdown reduce rotenone-induced H9C2 cells death via autophagy and anti-oxidative stress pathway.
CONCLUSION: siRNA-mediated GAPDH knockdown reduced rotenone-induced H9C2 cell death occurring via autophagy and anti-oxidative stress pathway. This study enriches the understanding of GAPDH pathophysiology role, and provides potential new therapeutic targets for cardiac disease states characterized by oxidative stress. PMID: 25725130 [PubMed - as supplied by publisher]
Source: Toxicology Letters - February 25, 2015 Category: Toxicology Authors: Liang S, Figtree G, Aiqun M, Ping Z Tags: Toxicol Lett Source Type: research

Cynaropicrin attenuates UVB-induced oxidative stress via the AhR-Nrf2-Nqo1 pathway.
Abstract Due to its antioxidant and anti-inflammatory activities, artichoke (Cynara scolymus) has been used as folk medicine to treat various diseases. Cynaropicrin (Cyn), a sesquiterpene lactone, is the major bioactive phytochemical in the artichoke; however, its pharmacological mechanism remains unknown. Because some phytochemicals exert their antioxidant activity by activating aryl hydrocarbon receptor (AhR), leading to subsequent induction of the antioxidant pathway including nuclear factor E2-related factor 2 (Nrf2) and NAD(P)H:quinone oxidoreductase 1 (Nqo1), we investigated whether Cyn also activates the Ah...
Source: Toxicology Letters - February 11, 2015 Category: Toxicology Authors: Takei K, Hashimoto-Hachiya A, Takahara M, Tsuji G, Nakahara T, Furue M Tags: Toxicol Lett Source Type: research

Ligand-independent activation of aryl hydrocarbon receptor signaling in PCB3-quinone treated HaCaT human keratinocytes.
Abstract Aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that plays a critical role in metabolism, cell proliferation, development, carcinogenesis, and xenobiotic response. In general, dioxin-like polychlorinated biphenyls (PCBs) exhibit a ligand-dependent activation of AhR-signaling. Results from this study show that a quinone-derivative (1-(4-Chlorophenyl)-benzo-2,5-quinone; 4-ClBQ) of a non-dioxin like PCB (PCB3) also activates AhR-signaling. Treatments of HaCaT human keratinocytes with 4-ClBQ and dioxin-like PCB126 significantly increased AhR-target gene expression, CYP1A1 mRNA and p...
Source: Toxicology Letters - February 7, 2015 Category: Toxicology Authors: Xiao W, Son J, Vorrink SU, Domann FE, Goswami PC Tags: Toxicol Lett Source Type: research