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Source: Toxicology Letters
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Total 70 results found since Jan 2013.

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

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

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

p-Cresol mediates autophagic cell death in renal proximal tubular cells.
Abstract Higher serum level of p-cresol (PC) in chronic kidney disease (CKD) patients has been linked with CKD progression. The toxic effect of PC on diverse cells has been reported by prior studies, except for renal tubular cells. Both autophagy and apoptosis contribute to renal tubular cell death, yet evidence of its response to PC is limited and their crosstalk is still unclear. Autophagy is an important cellular process involved in toxin-induced cell death. Renal tubular cell death in tubular injury is thought to be one of the key events causing the progression of CKD. Thus, we treated rat (NRK-52E) and human ...
Source: Toxicology Letters - February 7, 2015 Category: Toxicology Authors: Lin HH, Huang CC, Lin TY, Lin CY Tags: Toxicol Lett Source Type: research

Role of autophagy in arsenite-induced neurotoxicity: the involvement of α-synuclein.
Abstract In the present study, the role of autophagy in sodium arsenite (arsenite)-induced neurotoxicity was investigated in rat primary cultured cortical neurons. Incubation with arsenite concentration-dependently increased LC3-II levels (a biomarker of autophagy), indicating that arsenite is capable of inducing autophagy. Co-localization of fluorescent puncta of monodansylcadaverine (a fluorescent dye of autophagic vacuoles) and LysoTracker Red (a fluorescent dye of lysosomes) as well as chloroquine-induced enhancement of arsenite-elevated LC3-II levels suggest that arsenite induced autolysosome formation in pri...
Source: Toxicology Letters - January 29, 2015 Category: Toxicology Authors: Teng YC, Jeng CJ, Huang HJ, Lin AM Tags: Toxicol Lett Source Type: research

17-beta estradiol inhibits oxidative stress-induced accumulation of AIF into nucleolus and PARP1-dependent cell death via estrogen receptor alpha.
Abstract Oxidative stress-induced DNA damage results in over-activation of poly(ADP-ribose) polymerase 1 (PARP1), leading to parthanatos, a newly discovered cell elimination pathway. Inhibition of PARP1-dependent cell death has shown to improve the outcome of diseases, including stroke, heart ischemia, and neurodegenerative diseases. In the present study we aimed to detect whether estrogen plays a protective role in inhibiting parthanatos. We utilized human mammary adenocarcinoma cells (MCF7) that abundantly express the estrogen receptor alpha and beta (ERα and ERβ). Parthanatos was induced by challenging the ce...
Source: Toxicology Letters - September 30, 2014 Category: Toxicology Authors: Batnasan E, Wang R, Wen J, Ke Y, Li X, Bohio AA, Zeng X, Huo H, Han L, Boldogh I, Ba X Tags: Toxicol Lett Source Type: research

Nanomolar levels of PAHs in extracts from urban air induce MAPK signaling in HepG2cells.
This study has investigated intracellular MAPK signaling in response to PAHs in extracts from urban air collected in Stockholm, Sweden and Limeira, Brazil, in comparison to BP in HepG2cells. Nanomolar concentrations of PAHs in the extracts induced activation of MEK4 signaling with down-stream increased gene expression of several important stress response mediators. Involvement of the MEK4/JNK pathway was confirmed using siRNA and an inhibitor of JNK signaling resulting in significantly reduced MAPK signaling transactivated by the AP-1 transcription factors ATF2 and cJun. ATF2 was also identified as a sensitive stress respo...
Source: Toxicology Letters - June 6, 2014 Category: Toxicology Authors: Jarvis IW, Bergvall C, Morales DA, Kummrow F, Umbuzeiro GA, Westerholm R, Stenius U, Dreij K Tags: Toxicol Lett Source Type: research

Salvianolic acid B protects against acute ethanol-induced liver injury through SIRT1-mediated deacetylation of p53 in rats.
This study aimed to investigate the effect of SalB on acute ethanol-induced hepatic injury in rats and to explore the role of SIRT1 in this process. The results showed that pretreatment with SalB significantly reduced ethanol-induced elevation in aminotransferase activities, decreased hepatotoxic cytokine levels such as Interleukin-6 (IL-6), and increased the antioxidant enzyme activity. Moreover, SalB pretreatment reversed the increase in NF-κB, cleaved caspase-3 and decrease in B-cell lymphoma-extra large (Bcl-xL) caused by ethanol exposure. Importantly, SalB pretreatment significantly increased the expression of SIRT1,...
Source: Toxicology Letters - April 21, 2014 Category: Toxicology Authors: Li M, Lu Y, Hu Y, Zhai X, Xu W, Jing H, Tian X, Lin Y, Gao D, Yao J Tags: Toxicol Lett Source Type: research

Ziyuglycoside II induces cell cycle arrest and apoptosis through activation of ROS/JNK pathway in human breast cancer cells.
In this study, the anti-proliferative effect of ziyuglycoside II in two classic human breast cancer cell lines, MCF-7 and MDA-MB-231, was extensively investigated. Our study indicated that ziyuglycoside II could effectively induce G2/M phase arrest and apoptosis in both cell lines. Cell cycle blocking was associated with the down-regulation of Cdc25C, Cdc2, cyclin A and cyclin B1 as well as the up-regulation of p21/WAF1, phospho-Cdc25C and phospho-Cdc2. Ziyuglycoside II treatment also induced reactive oxygen species (ROS) production and apoptosis by activating the extrinsic/Fas/FasL pathway as well as the intrinsic/mitocho...
Source: Toxicology Letters - March 27, 2014 Category: Toxicology Authors: Zhu X, Wang K, Zhang K, Zhu L, Zhou F Tags: Toxicol Lett Source Type: research

Zinc Oxide nanoparticles induce Apoptosis by enhancement of Autophagy via PI3K/Akt/mTOR inhibition.
This study demonstrates autophagy supports apoptosis on ZnO NPs exposure. PMID: 24614525 [PubMed - as supplied by publisher]
Source: Toxicology Letters - March 7, 2014 Category: Toxicology Authors: Roy R, Singh SK, Chauhan LK, Das M, Tripathi A, Dwivedi PD Tags: Toxicol Lett Source Type: research

Downregulation of Rad51 participates in OTA-induced DNA double-strand breaks in GES-1 cells in vitro.
Abstract Ochratoxin A (OTA), a mycotoxin produced by ubiquitous Aspergilli, is carcinogenic, teratogenic, and nephrotoxic in both humans and animals. Our previous study found that OTA induced DNA double-strand breaks (DSBs) and resulted in G2 phase arrest in human gastric epithelium immortalized (GES-1) cells. DSBs can cause genomic instability, mutations, and neoplastic transformations, and improper repair of DSBs may lead to the development of cancer. Rad51 is a key protein in the homologous recombination (HR) pathway of DSBs repair. The roles of Rad51 in the repair of DNA damage vary in response to different ty...
Source: Toxicology Letters - February 10, 2014 Category: Toxicology Authors: Lian H, Cui J, Wang Y, Liu J, Wang J, Shen H, Xing L, Wang J, Yan X, Zhang X Tags: Toxicol Lett Source Type: research

The NF-κB family member RelB regulates microRNA miR-146a to suppress cigarette smoke-induced COX-2 protein expression in lung fibroblasts.
In this study we tested whether RelB attenuation of cigarette smoke-induced COX-2 protein is due to miR-146a. Utilizing pulmonary fibroblasts deficient in RelB expression, together with siRNA knock-down of RelB, we show the essential role of RelB in diminishing smoke-induced COX-2 protein expression despite robust activation of the canonical NF-κB pathway and subsequent induction of Cox-2 mRNA. RelB did not regulate COX-2 protein expression at the level of mRNA stability. Basal levels of miR-146a were significantly lower in Relb-deficient cells and cigarette smoke increased miR-146a expression only in Relb-expressing cell...
Source: Toxicology Letters - January 25, 2014 Category: Toxicology Authors: Zago M, de Souza AR, Hecht E, Rousseau S, Hamid Q, Eidelman DH, Baglole CJ Tags: Toxicol Lett Source Type: research

Celecoxib potentially inhibits metastasis of lung cancer promoted by surgery in mice, via suppression of the PGE2-modulated β-catenin pathway.
In conclusion, celecoxib inhibits metastasis of A549 cells in the circulation enhanced by PGE2 after surgery by not only inhibiting endogenous PGE2 expression, but also by suppression downstream of PGE2 via the GSK-3β-β-catenin pathway. PMID: 24374173 [PubMed - as supplied by publisher]
Source: Toxicology Letters - December 24, 2013 Category: Toxicology Authors: Zhang S, Da L, Yang X, Feng D, Yin R, Li M, Zhang Z, Jiang F, Xu L Tags: Toxicol Lett Source Type: research