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Source: PLoS One
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Total 74 results found since Jan 2013.
Sphingosine-1-Phosphate Is a Novel Regulator of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Activity
by Firhan A. Malik, Anja Meissner, Illya Semenkov, Steven Molinski, Stan Pasyk, Saumel Ahmadi, Hai H. Bui, Christine E. Bear, Darcy Lidington, Steffen-Sebastian Bolz
The cystic fibrosis transmembrane conductance regulator (CFTR) attenuates sphingosine-1-phosphate (S1P) signaling in resistance arteries and has emerged as a prominent regulator of myogenic vasoconstriction. This investigation demonstrates that S1P inhibits CFTR activity via adenosine monophosphate-activated kinase (AMPK), establishing a potential feedback link. In Baby Hamster Kidney (BHK) cells expressing wild-type human CFTR, S1P (1μmol/L) attenuates fors...
Source: PLoS One - June 16, 2015 Category: Biomedical Science Authors: Firhan A. Malik et al. Source Type: research
Molecular Modification of Metadherin/MTDH Impacts the Sensitivity of Breast Cancer to Doxorubicin
Conclusion MTDH gene plays a promoting role in the proliferation of breast cancer cells and its high expression may be associated with doxorubicin sensitivity of breast cancer.
Source: PLoS One - May 19, 2015 Category: Biomedical Science Authors: Zhenchuan Song et al. Source Type: research
Lipopolysaccharide (LPS)-Induced Biliary Epithelial Cell NRas Activation Requires Epidermal Growth Factor Receptor (EGFR)
by Christy E. Trussoni, James H. Tabibian, Patrick L. Splinter, Steven P. O’Hara
Cholangiocytes (biliary epithelial cells) actively participate in microbe-induced proinflammatory responses in the liver and contribute to inflammatory and infectious cholangiopathies. We previously demonstrated that cholangiocyte TLR-dependent NRas activation contributes to proinflammatory/ proliferative responses. We test the hypothesis that LPS-induced activation of NRas requires the EGFR. SV40-transformed human cholangiocytes (H69 cells), or low passage normal human cholangiocytes (NHC), were treated with LPS in the presence or absence ...
Source: PLoS One - April 27, 2015 Category: Biomedical Science Authors: Christy E. Trussoni et al. Source Type: research
Inducible but Not Constitutive Expression of PD-L1 in Human Melanoma Cells Is Dependent on Activation of NF-κB
by Kavitha Gowrishankar, Dilini Gunatilake, Stuart J. Gallagher, Jessamy Tiffen, Helen Rizos, Peter Hersey
Monoclonal antibodies against immune checkpoint blockade have proven to be a major success in the treatment of melanoma. The programmed death receptor-1 ligand-1 (PD-L1) expression on melanoma cells is believed to have an inhibitory effect on T cell responses and to be an important escape mechanism from immune attack. Previous studies have shown that PD-L1 can be expressed constitutively or can be induced by IFN-γ secreted by infiltrating lymphocytes. In the present study we have investigated the mechanism underlyin...
Source: PLoS One - April 6, 2015 Category: Biomedical Science Authors: Kavitha Gowrishankar et al. Source Type: research
IL-24 Inhibits Lung Cancer Cell Migration and Invasion by Disrupting The SDF-1/CXCR4 Signaling Axis
Conclusions IL-24 disrupts the SDF-1/CXCR4 signaling pathway and inhibits lung tumor cell migration and invasion. Additionally, IL-24, when combined with CXCR4 inhibitors exhibited enhanced anti-metastatic activity and is an attractive therapeutic strategy for lung metastasis.
Source: PLoS One - March 16, 2015 Category: Biomedical Science Authors: Janani Panneerselvam et al. Source Type: research
Viral Infection of Human Lung Macrophages Increases PDL1 Expression via IFNβ
by Karl J. Staples, Ben Nicholas, Richard T. McKendry, C. Mirella Spalluto, Joshua C. Wallington, Craig W. Bragg, Emily C. Robinson, Kirstin Martin, Ratko Djukanović, Tom M. A. Wilkinson
Lung macrophages are an important defence against respiratory viral infection and recent work has demonstrated that influenza-induced macrophage PDL1 expression in the murine lung leads to rapid modulation of CD8+ T cell responses via the PD1 receptor. This PD1/PDL1 pathway may downregulate acute inflammatory responses to prevent tissue damage. The aim of this study was to investigate the mechanisms of PDL1 regulation by human macrophage...
Source: PLoS One - March 16, 2015 Category: Biomedical Science Authors: Karl J. Staples et al. Source Type: research
Angiopoietin-1 Requires Oxidant Signaling through p47phox to Promote Endothelial Barrier Defense
Conclusions These results suggest an essential role for NOX signaling in Angpt-1-mediated endothelial barrier defense against mediators of systemic inflammation. More broadly, oxidants generated for signal transduction may have a barrier-promoting role in vascular endothelium.
Source: PLoS One - March 11, 2015 Category: Biomedical Science Authors: Chandra C. Ghosh et al. Source Type: research
HIF-1α Activation by Intermittent Hypoxia Requires NADPH Oxidase Stimulation by Xanthine Oxidase
by Jayasri Nanduri, Damodara Reddy Vaddi, Shakil A. Khan, Ning Wang, Vladislav Makarenko, Gregg L. Semenza, Nanduri R. Prabhakar
Hypoxia-inducible factor 1 (HIF-1) mediates many of the systemic and cellular responses to intermittent hypoxia (IH), which is an experimental model that simulates O2 saturation profiles occurring with recurrent apnea. IH-evoked HIF-1α synthesis and stability are due to increased reactive oxygen species (ROS) generated by NADPH oxidases, especially Nox2. However, the mechanisms by which IH activates Nox2 are not known. We recently reported that IH activates xanthine oxidase (XO) and the resulti...
Source: PLoS One - March 9, 2015 Category: Biomedical Science Authors: Jayasri Nanduri et al. Source Type: research
A γ-Secretase Inhibitor, but Not a γ-Secretase Modulator, Induced Defects in BDNF Axonal Trafficking and Signaling: Evidence for a Role for APP
We report that GSI disrupted retrograde axonal trafficking of brain-derived neurotrophic factor (BDNF), suppressed BDNF-induced downstream signaling pathways and induced changes in the distribution within neuronal processes of mitochondria and synaptic vesicles. In contrast, treatment with a novel class of GSMs had no significant effect on these measures. Since knockdown of APP by specific siRNA prevented GSI-induced changes in BDNF axonal trafficking and signaling, we concluded that GSI effects on APP processing were responsible, at least in part, for BDNF trafficking and signaling deficits. Our findings argue that with r...
Source: PLoS One - February 24, 2015 Category: Biomedical Science Authors: April M. Weissmiller et al. Source Type: research
Inhibitory Mechanism of FAT4 Gene Expression in Response to Actin Dynamics during Src-Induced Carcinogenesis
In this study, we show that transient activation of the Src oncoprotein represses FAT4 mRNA expression through actin depolymerization in the immortalized normal human mammary epithelial cell line MCF-10A. Src activation causes actin depolymerization via the MEK/Erk/Cofilin cascade. The MEK inhibitor U0126 blocks the inhibitory effect of Src on FAT4 mRNA expression and Src-induced actin depolymerization. To determine whether actin dynamics act on the regulation of FAT4 mRNA expression, we treated MCF-10A cells with the ROCK inhibitor Y-27632. Y-27632 treatment decreased FAT4 mRNA expression. This suppressive effect was bloc...
Source: PLoS One - February 13, 2015 Category: Biomedical Science Authors: Takao Ito et al. Source Type: research
TNF-α Mediates PKCδ/JNK1/2/c-Jun-Dependent Monocyte Adhesion via ICAM-1 Induction in Human Retinal Pigment Epithelial Cells
by I-Ta Lee, Shiau-Wen Liu, Pei-Ling Chi, Chih-Chung Lin, Li-Der Hsiao, Chuen-Mao Yang
Retinal inflammatory diseases induced by cytokines, such as tumor necrosis factor-α (TNF-α) are associated with an up-regulation of intercellular adhesion molecule-1 (ICAM-1) in the retinal pigment epithelial cells (RPECs). Retinal pigment epithelium (RPE) is a monolayer of epithelial cells that forms the outer blood-retinal barrier in the posterior segment of the eye, and is also implicated in the pathology of, such as neovascularization in age-related macular degeneration (AMD). However, the detailed mechanisms of TNF-α-induced ICA...
Source: PLoS One - February 12, 2015 Category: Biomedical Science Authors: I-Ta Lee et al. Source Type: research
Inhibitor of DNA Binding 4 (ID4) Is Highly Expressed in Human Melanoma Tissues and May Function to Restrict Normal Differentiation of Melanoma Cells
by Yuval Peretz, Hong Wu, Shayan Patel, Alfonso Bellacosa, Richard A. Katz
Melanoma tissues and cell lines are heterogeneous, and include cells with invasive, proliferative, stem cell-like, and differentiated properties. Such heterogeneity likely contributes to the aggressiveness of the disease and resistance to therapy. One model suggests that heterogeneity arises from rare cancer stem cells (CSCs) that produce distinct cancer cell lineages. Another model suggests that heterogeneity arises through reversible cellular plasticity, or phenotype-switching. Recent work indicates that phenotype-switching may include the abilit...
Source: PLoS One - February 2, 2015 Category: Biomedical Science Authors: Yuval Peretz et al. Source Type: research
Upregulation of Unc-51-Like Kinase 1 by Nitric Oxide Stabilizes SIRT1, Independent of Autophagy
by Junhui Xing, Hongtao Liu, Huabing Yang, Rui Chen, Yuguo Chen, Jian Xu
SIRT1 is central to the lifespan and vascular health, but undergoes degradation that contributes to several medical conditions, including diabetes. How SIRT1 turnover is regulated remains unclear. However, emerging evidence suggests that endothelial nitric oxide synthase (eNOS) positively regulates SIRT1 protein expression. We recently identified NO as an endogenous inhibitor of 26S proteasome functionality with a cellular reporter system. Here we extended this finding to a novel pathway that regulates SIRT1 protein breakdown. In cycloheximide (CHX)-...
Source: PLoS One - December 26, 2014 Category: Biomedical Science Authors: Junhui Xing et al. Source Type: research
MYC Is an Early Response Regulator of Human Adipogenesis in Adipose Stem Cells
by Chad Deisenroth, Michael B. Black, Salil Pendse, Linda Pluta, Sam M. Witherspoon, Patrick D. McMullen, Russell S. Thomas
Adipose stem cell (ASC) differentiation is necessary for the proper maintenance and function of adipose tissue. The procurement and characterization of multipotent ASCs has enabled investigation into the molecular determinants driving human adipogenesis. Here, the transcription factor MYC was identified as a significant regulator of ASC differentiation. Expression of MYC transcript and protein was found to accumulate during the initial course of differentiation. Loss-of-function analysis using siRNA ...
Source: PLoS One - December 1, 2014 Category: Biomedical Science Authors: Chad Deisenroth et al. Source Type: research
