Double-stranded RNA upregulates the expression of inflammatory mediators in human aortic valve cells through the TLR3-TRIF-noncanonical NF-{kappa}B pathway
The objective of this study is to determine the effect of dsRNA on AVIC inflammatory responses and the underlying mechanism. AVICs from normal human aortic valves were stimulated with polyinosinic-polycytidylic acid [poly(I:C)], a mimic of dsRNA. Poly(I:C) increased the production of IL-6, IL-8, monocyte chemoattractant protein-1, and ICAM-1. Poly(I:C) also induced robust activation of ERK1/2 and NF-B. Knockdown of Toll-like receptor 3 (TLR3) or Toll-IL-1 receptor domain-containing adapter-inducing IFN-β (TRIF) suppressed ERK1/2 and NF-B p65 phosphorylation and reduced inflammatory mediator production induced by poly(...
Source: AJP: Cell Physiology - April 7, 2017 Category: Cytology Authors: Zhan, Q., Song, R., Li, F., Ao, L., Zeng, Q., Xu, D., Fullerton, D. A., Meng, X. Tags: RESEARCH ARTICLE Source Type: research
Mitochondrial connexin40 regulates mitochondrial calcium uptake in coronary endothelial cells
Connexins (Cxs) are a group of integral membrane proteins that can form gap junctions between adjacent cells. Recently, it was reported that Cx43 is expressed not only in the plasma membrane but also in the inner mitochondrial membrane and that it regulates mitochondrial functions. Cx40 is predominantly expressed in vascular endothelial cells (ECs) and plays an important role in the electrical propagation between ECs and endothelial/smooth muscle cells. However, it is unknown whether Cx40 is expressed in the mitochondria and what the role of mitochondrial Cx40 is in endothelial functions. We observed in coronary ECs that C...
Source: AJP: Cell Physiology - April 7, 2017 Category: Cytology Authors: Guo, R., Si, R., Scott, B. T., Makino, A. Tags: RESEARCH ARTICLE Source Type: research
Na-K-ATPase regulates intercellular communication in the vascular wall via cSrc kinase-dependent connexin43 phosphorylation
Communication between vascular smooth muscle cells (VSMCs) is dependent on gap junctions and is regulated by the Na-K-ATPase. The Na-K-ATPase is therefore important for synchronized VSMC oscillatory activity, i.e., vasomotion. The signaling between the Na-K-ATPase and gap junctions is unknown. We tested here the hypothesis that this signaling involves cSrc kinase. Intercellular communication was assessed by membrane capacitance measurements of electrically coupled VSMCs. Vasomotion in isometric myograph, input resistance, and synchronized [Ca2+]i transients were used as readout for intercellular coupling in rat mesenteric ...
Source: AJP: Cell Physiology - April 7, 2017 Category: Cytology Authors: Hangaard, L., Bouzinova, E. V., Staehr, C., Dam, V. S., Kim, S., Xie, Z., Aalkjaer, C., Matchkov, V. V. Tags: RESEARCH ARTICLE Source Type: research
Lipopolysaccharide inhibits colonic biotin uptake via interference with membrane expression of its transporter: a role for a casein kinase 2-mediated pathway
This study shows for the first time that LPS inhibits colonic biotin uptake via decreasing membrane expression of its transporter and that these effects likely involve a CK2-mediated pathway. (Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - April 1, 2017 Category: Cytology Authors: Lakhan, R., Said, H. M. Tags: RESEARCH ARTICLE Source Type: research
c-Jun enhances intestinal epithelial restitution after wounding by increasing phospholipase C-{gamma}1 transcription
c-Jun is an activating protein 1 (AP-1) transcription factor and implicated in many aspects of cellular functions, but its exact role in the regulation of early intestinal epithelial restitution after injury remains largely unknown. Phospholipase C-1 (PLC1) catalyzes hydrolysis of phosphatidylinositol 4,5 biphosphate into the second messenger diacylglycerol and inositol 1,4,5 triphosphate, coordinates Ca2+ store mobilization, and regulates cell migration and proliferation in response to stress. Here we reported that c-Jun upregulates PLC1 expression and enhances PLC1-induced Ca2+ signaling, thus promoting intestinal epithe...
Source: AJP: Cell Physiology - April 1, 2017 Category: Cytology Authors: Wang, P.-Y., Wang, S. R., Xiao, L., Chen, J., Wang, J.-Y., Rao, J. N. Tags: RESEARCH ARTICLE Source Type: research
Effects of Pseudomonas aeruginosa on CFTR chloride secretion and the host immune response
In the healthy lung the opportunistic pathogen, Pseudomonas aeruginosa, is rapidly eliminated by mucociliary clearance, a process that is dependent on the activity of the CFTR anion channel that, in concert with a number of other transport proteins, regulates the volume and composition of the periciliary surface liquid. This fluid layer is essential to enable cilia to clear pathogens from the lungs. However, in cystic fibrosis (CF), mutations in the CFTR gene reduce Cl– and HCO3– secretion, thereby decreasing periciliary surface liquid volume and mucociliary clearance of bacteria. In CF this leads to persistent...
Source: AJP: Cell Physiology - April 1, 2017 Category: Cytology Authors: Stanton, B. A. Tags: REVIEW Source Type: research
Onward and upward with transparent research reporting
(Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - April 1, 2017 Category: Cytology Authors: Adams, J. C. Tags: EDITORIAL Source Type: research
ATF6 knockdown decreases apoptosis, arrests the S phase of the cell cycle, and increases steroid hormone production in mouse granulosa cells
Activating transcription factor 6 (ATF6), a sensor protein located in the endoplasmic reticulum (ER) membrane, is an important factor in the ER stress signaling pathway. ER stress is known to be involved in folliculogenesis, follicular growth, and ovulation; however, the physiological function of ATF6 in mouse granulosa cells remains largely unknown. The aim of this study was to assess the role of ATF6 in mouse granulosa cells with respect to apoptosis, the cell cycle, and steroid hormone production, as well as several key genes related to follicular development, via RNA interference, immunohistochemical staining, real-tim...
Source: AJP: Cell Physiology - March 9, 2017 Category: Cytology Authors: Xiong, Y., Chen, H., Lin, P., Wang, A., Wang, L., Jin, Y. Tags: RESEARCH ARTICLE Source Type: research
Quantification of growth factor signaling and pathway cross talk by live-cell imaging
Peptide growth factors stimulate cellular responses through activation of their transmembrane receptors. Multiple intracellular signaling cascades are engaged following growth factor–receptor binding, leading to short- and long-term biological effects. Each receptor-activated signaling pathway does not act in isolation but rather interacts at different levels with other pathways to shape signaling networks that are distinctive for each growth factor. To gain insights into the specifics of growth factor-regulated interactions among different signaling cascades, we developed a HeLa cell line stably expressing fluoresce...
Source: AJP: Cell Physiology - March 9, 2017 Category: Cytology Authors: Gross, S. M., Rotwein, P. Tags: RESEARCH ARTICLE Source Type: research
S-nitrosylation and S-glutathionylation of Cys134 on troponin I have opposing competitive actions on Ca2+ sensitivity in rat fast-twitch muscle fibers
Nitric oxide is generated in skeletal muscle with activity and decreases Ca2+ sensitivity of the contractile apparatus, putatively by S-nitrosylation of an unidentified protein. We investigated the mechanistic basis of this effect and its relationship to the oxidation-induced increase in Ca2+ sensitivity in mammalian fast-twitch (FT) fibers mediated by S-glutathionylation of Cys134 on fast troponin I (TnIf). Force-[Ca2+] characteristics of the contractile apparatus in mechanically skinned fibers were assessed by direct activation with heavily Ca2+-buffered solutions. Treatment with S-nitrosylating agents, S-nitrosoglutathi...
Source: AJP: Cell Physiology - March 9, 2017 Category: Cytology Authors: Dutka, T. L., Mollica, J. P., Lamboley, C. R., Weerakkody, V. C., Greening, D. W., Posterino, G. S., Murphy, R. M., Lamb, G. D. Tags: RESEARCH ARTICLE Source Type: research
A two-faced cysteine residue modulates skeletal muscle contraction. Focus on "S-nitrosylation and S-glutathionylation of Cys134 on troponin I have opposing competitive actions on Ca2+ sensitivity in rat fast-twitch muscle fibers
(Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - March 9, 2017 Category: Cytology Authors: de Winter, J. M., Ottenheijm, C. A. C. Tags: EDITORIAL FOCUS Source Type: research
Biological signaling by carbon monoxide and carbon monoxide-releasing molecules
Carbon monoxide (CO) is continuously produced in mammalian cells during the degradation of heme. It is a stable gaseous molecule that reacts selectively with transition metals in a specific redox state, and these characteristics restrict the interaction of CO with defined biological targets that transduce its signaling activity. Because of the high affinity of CO for ferrous heme, these targets can be grouped into heme-containing proteins, representing a large variety of sensors and enzymes with a series of diverse function in the cell and the organism. Despite this notion, progress in identifying which of these targets ar...
Source: AJP: Cell Physiology - March 9, 2017 Category: Cytology Authors: Motterlini, R., Foresti, R. Tags: THEME Source Type: research
Myelo-erythroid commitment after burn injury is under {beta}-adrenergic control via MafB regulation
This study illustrates how conditions resulting in a high catecholamine microenvironment such as burns can instigate myelo-erythroid reprioritization influenced by β-adrenergic stimulation leading to anemia. In a mouse model of scald burn injury, we observed, along with a threefold increase in bone marrow LSK cells (linneg Sca1+cKit+), that the myeloid shift is accompanied with a significant reduction in megakaryocyte erythrocyte progenitors (MEPs). β-Blocker administration (propranolol) for 6 days after burn, not only reduced the number of LSKs and MafB+ cells in multipotent progenitors, but also influenced myel...
Source: AJP: Cell Physiology - March 2, 2017 Category: Cytology Authors: Hasan, S., Johnson, N. B., Mosier, M. J., Shankar, R., Conrad, P., Szilagyi, A., Gamelli, R. L., Muthumalaiappan, K. Tags: RESEARCH ARTICLE Source Type: research
TAZ activation drives fibroblast spheroid growth, expression of profibrotic paracrine signals, and context-dependent ECM gene expression
Recent studies have implicated the Hippo pathway and its transcriptional effectors YAP and TAZ as necessary for fibroblast activation and tissue fibrosis. To test the specific and sufficient roles for TAZ in driving autonomous fibroblast activation, we cultured NIH3T3 fibroblasts expressing a doxycycline-inducible nuclear-localized mutant of TAZ (TAZ4SA) in scaffold-free 3D hanging drop spheroids, or on matrices of specified mechanical rigidity. Control NIH3T3 fibroblasts formed spheroids in hanging drop culture that remained stable and neither increased nor decreased in size significantly over 15 days. In contrast, TAZ4SA...
Source: AJP: Cell Physiology - March 2, 2017 Category: Cytology Authors: Jorgenson, A. J., Choi, K. M., Sicard, D., Smith, K. M. J., Hiemer, S. E., Varelas, X., Tschumperlin, D. J. Tags: RESEARCH ARTICLE Source Type: research
Keeping fibroblasts in suspense: TAZ-mediated signaling activates a context-dependent profibrotic phenotype. Focus on "TAZ activation drives fibroblast spheroid growth, expression of profibrotic paracrine signals, and context-dependent ECM gene expression"
(Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - March 2, 2017 Category: Cytology Authors: Piersma, B., Bank, R. A. Tags: EDITORIAL FOCUS Source Type: research
