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Source: Toxicology and Applied Pharmacology

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Total 118 results found since Jan 2013.

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

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

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

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

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

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

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

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

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

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

Arsenic silences hepatic PDK4 expression through activation of histone H3K9 methylatransferase G9a.
Abstract It is well established that increased liver cancer incidence is strongly associated with epigenetic silencing of tumor suppressor genes; the latter is contributed by the environmental exposure to arsenic. Pyruvate dehydrogenase kinase 4 (PDK4) is a mitochondrial protein that regulates the TCA cycle. However, the epigenetic mechanisms mediated by arsenic to control PDK4 expression remain elusive. In the present study, we showed that histone methyltrasferase G9a- and Suv39H-mediated histone H3 lysine 9 (H3K9) methylations contributed to PDK4 silencing in hepatic cells. The PDK4 expression was induced by G9a...
Source: Toxicology and Applied Pharmacology - May 19, 2016 Category: Toxicology Authors: Zhang X, Wu J, Choiniere J, Yang Z, Huang Y, Bennett J, Wang L Tags: Toxicol Appl Pharmacol Source Type: research

Epigenetic modification of miR-10a regulates renal damage by targeting CREB1 in type 2 diabetes mellitus.
In this study, we assessed the role of miR-10a in extracellular matrix accumulation in the kidney of diabetic mellitus induced by combining administration of chronic high fat diet (HFD) and low dosage of streptozotocin (STZ, 35mg/kg). Here, we found that HFD/STZ administration decreased the level of microRNA (miR-10a) expression in ICR strain mice. Overexpression of miR-10a alleviated the increased ratio of urine albumin-to-creatinine (ACR) ratio of HFD/STZ mice. In contrast, knockdown of miR-10a increased the ratio of kidney ACR in naïve mice. Furthermore, cAMP response element binding protein 1 (CREB1) was validated as ...
Source: Toxicology and Applied Pharmacology - June 8, 2016 Category: Toxicology Authors: Shan Q, Zheng G, Zhu A, Cao L, Lu J, Wu D, Zhang Z, Fan S, Sun C, Hu B, Zheng Y Tags: Toxicol Appl Pharmacol Source Type: research

Effect of TCDD on the fate of epithelial cells isolated from human fetal palatal shelves (hFPECs).
Abstract Cleft palate is caused by the failure of palatal midline epithelial cells to disintegrate, which is necessary for palatal mesenchymal confluence. Although 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) exposure is linked to cleft palate at a high rate, the mechanism remains to be elucidated. The present study was designed to determine the effects of TCDD on the fate of epithelial cell isolated from human fetal palatal shelves (hFPECs). We demonstrate that TCDD increased cell proliferation and promoted the progression of cells from G1 to S phase as well as increased the number of cells entering the G2/M phase....
Source: Toxicology and Applied Pharmacology - June 12, 2016 Category: Toxicology Authors: Gao Z, Bu Y, Zhang G, Liu X, Wang X, Ding S, Wang E, Shi R, Li Q, Fu J, Yu Z Tags: Toxicol Appl Pharmacol Source Type: research

Bifunctional Alkylating Agent-Mediated MGMT-DNA Cross-linking and its Proteolytic Cleavage in 16HBE Cells.
Abstract Nitrogen mustard (NM), a bifunctional alkylating agent (BAA), contains two alkyl arms and can act as a cross-linking bridge between DNA and protein to form a DNA-protein cross-link (DPC). O(6)-methylguanine-DNA methyltransferase (MGMT), a DNA repair enzyme for alkyl adducts removal, is found to enhance cell sensitivity to BAAs and to promote damage, possibly due to its stable covalent cross-linking with DNA mediated by BAAs. To investigate MGMT-DNA cross-link (mDPC) formation and its possible dual roles in NM exposure, human bronchial epithelial cell line 16HBE was subjected to different concentrations of...
Source: Toxicology and Applied Pharmacology - June 20, 2016 Category: Toxicology Authors: Cheng J, Ye F, Dan G, Zhao Y, Wang B, Zhao J, Sai Y, Zou Z Tags: Toxicol Appl Pharmacol Source Type: research

Hepatocyte-protective effect of nectandrin B, a nutmeg lignan, against oxidative stress: Role of Nrf2 activation through ERK phosphorylation and AMPK-dependent inhibition of GSK-3 β.
This study investigated the hepatocyte-protective effect of nectandrin B against tert-butylhydroperoxide-induced oxidative injury and the underlying molecular mechanism. The cell viability assay revealed that nectandrin B prevents apoptosis stimulated by tert-butylhydroperoxide in both HepG2 cells and primary mouse hepatocytes. Nectandrin B also attenuated ROS production and restored the depleted glutathione level. Real-time PCR and immunoblot analyses showed that the expression of glutamate-cysteine ligase, an enzyme responsible for the glutathione biosynthesis, was induced by nectandrin B, indicating its indirect antioxi...
Source: Toxicology and Applied Pharmacology - August 6, 2016 Category: Toxicology Authors: Song JS, Kim EK, Choi YW, Oh WK, Kim YM Tags: Toxicol Appl Pharmacol Source Type: research