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Source: Toxicology and Applied Pharmacology

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Total 118 results found since Jan 2013.

Mitochondrial-targeted aryl hydrocarbon receptor and the impact of 2,3,7,8-tetrachlorodibenzo-p-dioxin on cellular respiration and the mitochondrial proteome.
Abstract The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor within the Per-Arnt-Sim (PAS) domain superfamily. Exposure to the most potent AHR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), is associated with various pathological effects including metabolic syndrome. While research over the last several years has demonstrated a role for oxidative stress and metabolic dysfunction in AHR-dependent TCDD-induced toxicity, the role of the mitochondria in this process has not been fully explored. Our previous research suggested that a portion of the cellular pool of AHR could be found in ...
Source: Toxicology and Applied Pharmacology - April 18, 2016 Category: Toxicology Authors: Hwang HJ, Dornbos P, Steidemann M, Dunivin TK, Rizzo M, LaPres JJ Tags: Toxicol Appl Pharmacol Source Type: research

TCDD promoted EMT of hFPECs via AhR, which involved the activation of EGFR/ERK signaling.
Abstract One critical step of second palatal fusion is the newly formed medial epithelia seam (MES) disintegration, which involves apoptosis, epithelial to mesenchymal transition (EMT), and cell migration. Although the environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) produces cleft palate at high rates, little is known about the effects of TCDD exposure on the fate of palatal epithelial cells. By using primary epithelial cells isolated from human fetal palatal shelves (hFPECs), we show that TCDD increased cell proliferation and EMT, as demonstrated by increased the epithelial markers (E-cadherin a...
Source: Toxicology and Applied Pharmacology - March 10, 2016 Category: Toxicology Authors: Gao Z, Bu Y, Liu X, Wang X, Zhang G, Wang E, Ding S, Liu Y, Shi R, Li Q, Fu J, Yu Z Tags: Toxicol Appl Pharmacol Source Type: research

Cellular uptake of lead in the blood-cerebrospinal fluid barrier: Novel roles of Connexin 43 hemichannel and its down-regulations via Erk phosphorylation.
This study was designed to investigate the roles of Cx43 in Pb uptake in the epithelial cells. Autometallography was used to outline Pb's subcellular location, and the characteristics of Pb transport into CP cells, including concentration- and time-dependence were analyzed by atomic absorption spectroscopy. Knockdown/overexpression of Cx43 with transient siRNA/plasmids transfections before Pb exposure diminished/increased the Pb accumulation. In the Z310 cell-based doxycycline-inducible Cx43 expression cell line (iZCx43), doxycycline induced a significant increase (3-fold) in Pb uptake, corresponding to the increased Cx43 ...
Source: Toxicology and Applied Pharmacology - February 26, 2016 Category: Toxicology Authors: Song H, Zheng G, Liu Y, Shen XF, Zhao ZH, Aschner M, Luo WJ, Chen JY Tags: Toxicol Appl Pharmacol Source Type: research

Partial contribution of the Keap1-Nrf2 system to cadmium-mediated metallothionein expression in vascular endothelial cells.
Abstract Cadmium is an environmental electrophile that modifies protein reactive thiols such as Kelch-like ECH-associated protein 1 (Keap1), a negative regulator of nuclear factor-erythroid 2-related factor 2 (Nrf2). In the present study, we investigated a role of the Keap1-Nrf2 system in cellular response to cadmium in vascular endothelial cells. Exposure of bovine aortic endothelial cells to cadmium resulted in modification of Keap1 and Nrf2 activation, thereby up-regulating not only its typical downstream proteins but also metallothionein-1/2. Experiments with siRNA-mediated knockdown of Nrf2 or Keap1 supported...
Source: Toxicology and Applied Pharmacology - January 28, 2016 Category: Toxicology Authors: Shinkai Y, Kimura T, Itagaki A, Yamamoto C, Taguchi K, Yamamoto M, Kumagai Y, Kaji T Tags: Toxicol Appl Pharmacol Source Type: research

DNA damage-inducible transcript 4 (DDIT4) mediates methamphetamine-induced autophagy and apoptosis through mTOR signaling pathway in cardiomyocytes.
Abstract Methamphetamine (METH) is an amphetamine-like psychostimulant that is commonly abused. Previous studies have shown that METH can induce damages to the nervous system and recent studies suggest that METH can also cause adverse and potentially lethal effects on the cardiovascular system. Recently, we demonstrated that DNA damage-inducible transcript 4 (DDIT4) regulates METH-induced neurotoxicity. However, the role of DDIT4 in METH-induced cardiotoxicity remains unknown. We hypothesized that DDIT4 may mediate METH-induced autophagy and apoptosis in cardiomyocytes. To test the hypothesis, we examined DDIT4 pr...
Source: Toxicology and Applied Pharmacology - January 26, 2016 Category: Toxicology Authors: Chen R, Wang B, Chen L, Cai D, Li B, Chen C, Huang E, Liu C, Lin Z, Xie WB, Wang H Tags: Toxicol Appl Pharmacol Source Type: research

Role of NLRC5 in progression and reversal of hepatic fibrosis.
CONCLUSION: NLRC5 is differentially expressed in hepatic tissues and hepatic stellate cells during hepatic fibrosis and its reversal. All the data indicated that NLRC5 may play a crucial role in regulating the reversal of hepatic fibrosis through NF-κB signaling pathway. PMID: 26806094 [PubMed - as supplied by publisher]
Source: Toxicology and Applied Pharmacology - January 21, 2016 Category: Toxicology Authors: Liu X, Wu Y, Yang Y, Li W, Huang C, Meng X, Li J Tags: Toxicol Appl Pharmacol Source Type: research

PTP1B confers liver fibrosis by regulating the activation of hepatic stellate cells.
Abstract Liver fibrosis is a reversible wound-healing response to chronic hepatic injuries. Activation of hepatic stellate cells (HSCs) plays a pivotal role in the development of hepatic fibrosis. The currently accepted mechanism for the resolution of liver fibrosis is the apoptosis and inactivation of activated HSCs. Protein tyrosine phosphatase 1B (PTP1B), a prototype of non-receptor protein tyrosine phosphatase, is proved to be a vital modulator in cardiac fibrogenesis. However, the precise role of PTP1B on liver fibrosis and HSC activation is still unclear. Our study showed that the expression of PTP1B was ele...
Source: Toxicology and Applied Pharmacology - December 29, 2015 Category: Toxicology Authors: Chen PJ, Cai SP, Yang Y, Li WX, Huang C, Meng XM, Li J Tags: Toxicol Appl Pharmacol Source Type: research

Ghrelin protects against depleted uranium-induced apoptosis of MC3T3-E1 cells through oxidative stress-mediated p38-mitogen-activated protein kinase pathway.
This study evaluates the impact of ghrelin on DU-induced apoptosis of the osteoblast MC3T3-E1 and investigates its underlying mechanisms. The results show that ghrelin relieved the intracellular oxidative stress induced by DU, eliminated reactive oxygen species (ROS) and reduced lipid peroxidation by increasing intracellular GSH levels; in addition, ghrelin effectively suppressed apoptosis, enhanced mitochondrial membrane potential, and inhibited cytochrome c release and caspase-3 activation after DU exposure. Moreover, ghrelin significantly reduced the expression of DU-induced phosphorylated p38-mitogen-activated protein ...
Source: Toxicology and Applied Pharmacology - October 31, 2015 Category: Toxicology Authors: Hao Y, Liu C, Huang J, Gu Y, Li H, Yang Z, Liu J, Wang W, Li R Tags: Toxicol Appl Pharmacol Source Type: research

Continuous activation of Nrf2 and its target antioxidant enzymes leads to arsenite-induced malignant transformation of human bronchial epithelial cells.
Abstract Long-term exposure to arsenite leads to human lung cancer, but the underlying mechanisms of carcinogenesis remain obscure. The transcription factor of nuclear factor-erythroid-2 p45-related factor (Nrf2)-mediated antioxidant response represents a critical cellular defense mechanism and protection against various diseases. Paradoxically, emerging data suggest that the constitutive activation of Nrf2 is associated with cancer development, progression and chemotherapy resistance. However, the role of Nrf2 in the occurrence of cancer induced by long-term arsenite exposure remains to be fully understood. By es...
Source: Toxicology and Applied Pharmacology - September 26, 2015 Category: Toxicology Authors: Yang X, Wang D, Ma Y, Xu X, Zhu Z, Wang X, Deng H, Li C, Chen M, Tong J, Yamanaka K, An Y Tags: Toxicol Appl Pharmacol Source Type: research

Posttranscriptional silencing of the lncRNA MALAT1 by miR-217 inhibits the epithelial-mesenchymal transition via enhancer of zeste homolog 2 in the malignant transformation of HBE cells induced by cigarette smoke extract.
Abstract Lung cancer is regarded as the leading cause of cancer-related deaths, and cigarette smoking is one of the strongest risk factors for the development of lung cancer. However, the mechanisms for cigarette smoke-induced lung carcinogenesis remain unclear. The present study investigated the effects of an miRNA (miR-217) on levels of an lncRNA (MALAT1) and examined the role of these factors in the epithelial-mesenchymal transition (EMT) induced by cigarette smoke extract (CSE) in human bronchial epithelial (HBE) cells. In these cells, CSE caused decreases of miR-217 levels and increases in lncRNA MALAT1 level...
Source: Toxicology and Applied Pharmacology - September 25, 2015 Category: Toxicology Authors: Lu L, Luo F, Liu Y, Liu X, Shi L, Lu X, Liu Q Tags: Toxicol Appl Pharmacol Source Type: research

Cadmium promotes the proliferation of triple-negative breast cancer cells through EGFR-mediated cell cycle regulation.
Abstract Cadmium (Cd) is a carcinogenic metal which is implicated in breast cancer by epidemiological studies. It is reported to promote breast cancer cell growth in vitro through membrane receptors. The study described here examined Cd-mediated growth of non-metastatic human breast cancer derived cells that lack receptors for estrogen, progesterone, and HER2. Treatment of triple-negative HCC 1937 cells with 0.1-0.5μM Cd increased cell growth by activation of AKT and ERK. Accelerated cell cycle progression was achieved by increasing the levels of cyclins A, B, and E, as well as those of CDKs 1 and 2. Although tri...
Source: Toxicology and Applied Pharmacology - September 15, 2015 Category: Toxicology Authors: Wei Z, Song X, Shaikh ZA Tags: Toxicol Appl Pharmacol Source Type: research

Requirement of ERα and Basal Activities of EGFR and Src Kinase in Cd-induced Activation of MAP/ERK Pathway in Human Breast Cancer MCF-7 Cells.
This study explores the mechanism of Cd-induced activation of MAPK/ERK pathway. Specifically, the role of cell surface receptors ERα, EGFR, and Src kinase was evaluated in human breast cancer MCF-7 cells treated with 1-3 μM Cd. The activation of ERK was studied using a serum response element (SRE) luciferase reporter assay. Receptor phosphorylation was detected by Western blot analyses. Cd treatment increased both the SRE reporter activity and ERK1/2 phosphorylation in a concentration-dependent manner. Cd treatment had no effect on reactive oxygen species (ROS) generation. Also, blocking the entry of Cd into the cells wi...
Source: Toxicology and Applied Pharmacology - May 22, 2015 Category: Toxicology Authors: Song X, Wei Z, Shaikh ZA Tags: Toxicol Appl Pharmacol Source Type: research

Combined effects of EGFR tyrosine kinase inhibitors and vATPase inhibitors in NSCLC cells.
Abstract Despite excellent initial clinical responses of non-small cell lung cancer (NSCLC) patients to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), many patients eventually develop resistance. According to a recent report, vacuolar H+ ATPase (vATPase) is overexpressed and is associated with chemotherapy drug resistance in NSCLC. We investigated the combined effects of EGFR TKIs and vATPase inhibitors and their underlying mechanisms in the regulation of NSCLC cell death. We found that combined treatment with EGFR TKIs (erlotinib, gefitinib, or lapatinib) and vATPase inhibitors (bafilo...
Source: Toxicology and Applied Pharmacology - May 14, 2015 Category: Toxicology Authors: Jin HO, Hong SE, Kim CS, Park JA, Kim JH, Kim JY, Kim B, Chang YH, Hong SI, Hong YJ, Park IC, Lee JK Tags: Toxicol Appl Pharmacol Source Type: research

Dopamine induces growth inhibition and vascular normalization through reprograming M2-polarized macrophages in rat C6 glioma.
Abstract Dopamine (DA), a monoamine catecholamine neurotransmitter with antiangiogenic activity, stabilizes tumor vessels in colon, prostate and ovarian cancer, thus increases chemotherapeutic efficacy. Here, in the rat C6 glioma models, we investigated the vascular normalization effects of DA and its mechanisms of action. DA (25, 50 mg/kg) inhibited tumor growth, while a precursor of DA (levodopa) prolonged the survival time of rats bearing orthotopic C6 glioma. DA improved tumor perfusion, with significant effects from day 3, and a higher level at day 5 to 7. In addition, DA decreased microvessel density and hyp...
Source: Toxicology and Applied Pharmacology - March 25, 2015 Category: Toxicology Authors: Qin T, Wang C, Chen X, Duan C, Zhang X, Zhang J, Chai H, Tang T, Chen H, Yue J, Li Y, Yang J Tags: Toxicol Appl Pharmacol Source Type: research

Curcumin attenuates glutamate neurotoxicity in the hippocampus by suppression of ER stress-associated TXNIP/NLRP3 inflammasome activation in a manner dependent on AMPK.
This study aims to investigate the action of curcumin in the hippocampus subjected to glutamate neurotoxicity. Glutamate stimulation induced reactive oxygen species (ROS), endoplasmic reticulum stress (ER stress) and TXNIP/NLRP3 inflammasome activation, leading to the damage in the hippocampus. Curcumin treatment in the hippocampus or SH-SY5Y cells inhibited IRE1α and PERK phosphorylation with suppression of intracellular ROS production. Curcumin increased AMPK activity and knockdown of AMPKα with specific siRNA abrogated its inhibitory effects on IRE1α and PERK phosphorylation, indicating that AMPK activity was essenti...
Source: Toxicology and Applied Pharmacology - March 16, 2015 Category: Toxicology Authors: Li Y, Li J, Li S, Li Y, Wang X, Liu B, Fu Q, Ma S Tags: Toxicol Appl Pharmacol Source Type: research