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Source: FASEB Journal
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Total 33 results found since Jan 2013.
Beyond the brain: disrupted in schizophrenia 1 regulates pancreatic {beta}-cell function via glycogen synthase kinase-3{beta} Research Communication
Individuals with schizophrenia and their first-degree relatives have higher rates of type 2 diabetes (T2D) than the general population (18–30 vs. 1.2–6.3%), independent of body mass index and antipsychotic medication, suggesting shared genetic components may contribute to both diseases. The cause of this association remains unknown. Mutations in disrupted in schizophrenia 1 (DISC1) increase the risk of developing psychiatric disorders [logarithm (base 10) of odds = 7.1]. Here, we identified DISC1 as a major player controlling pancreatic β-cell proliferation and insulin secretion via regulation of glycogen ...
Source: FASEB Journal - February 1, 2016 Category: Biology Authors: Jurczyk, A., Nowosielska, A., Przewozniak, N., Aryee, K.-E., DiIorio, P., Blodgett, D., Yang, C., Campbell-Thompson, M., Atkinson, M., Shultz, L., Rittenhouse, A., Harlan, D., Greiner, D., Bortell, R. Tags: Research Communication Source Type: research
Abolition of mitochondrial substrate-level phosphorylation by itaconic acid produced by LPS-induced Irg1 expression in cells of murine macrophage lineage Research Communication
Itaconate is a nonamino organic acid exhibiting antimicrobial effects. It has been recently identified in cells of macrophage lineage as a product of an enzyme encoded by immunoresponsive gene 1 (Irg1), acting on the citric acid cycle intermediate cis-aconitate. In mitochondria, itaconate can be converted by succinate–coenzyme A (CoA) ligase to itaconyl-CoA at the expense of ATP (or GTP), and is also a weak competitive inhibitor of complex II. Here, we investigated specific bioenergetic effects of increased itaconate production mediated by LPS-induced stimulation of Irg1 in murine bone marrow–derived macrophage...
Source: FASEB Journal - January 5, 2016 Category: Biology Authors: Nemeth, B., Doczi, J., Csete, D., Kacso, G., Ravasz, D., Adams, D., Kiss, G., Nagy, A. M., Horvath, G., Tretter, L., Mocsai, A., Csepanyi-Kömi, R., Iordanov, I., Adam-Vizi, V., Chinopoulos, C. Tags: Research Communication Source Type: research
Extracellular matrix-induced Hic-5 expression in glomerular mesangial cells leads to a prosclerotic phenotype independent of TGF-{beta} Research Communication
Chronic fibroproliferative diseases account for approximately 45% of all deaths in the developed world. In the kidney, glomerulosclerosis is the underlying pathology in approximately half of patients with renal failure receiving dialysis. Mesangial cell expression of the LIM protein hydrogen peroxide-induced clone-5 (Hic-5) is important in its pathogenesis. Hic-5 expression increases following mesangial cell attachment to collagen I, associated with increased collagen I expression and increased susceptibility to apoptosis both in vitro and in experimental glomerulosclerosis. TGF-β has an established role in many fibro...
Source: FASEB Journal - December 1, 2015 Category: Biology Authors: Hornigold, N., Mooney, A. Tags: Research Communication Source Type: research
Elevated expression of periostin in human osteoarthritic cartilage and its potential role in matrix degradation via matrix metalloproteinase-13 Research Communication
We examined periostin expression by immunohistochemical analysis of lesional and nonlesional cartilage from human and rodent OA knee cartilage. In addition, we used small interfering (si)RNA and adenovirus transduction of chondrocytes to knock down and up-regulate periostin levels, respectively, and analyzed its effect on matrix metalloproteinase (MMP)-13, a disintegrin and MMP with thrombospondin motifs (ADAMTS)-4, and type II collagen expression. We found high periostin levels in human and rodent OA cartilage. Periostin increased MMP-13 expression dose [1–10 µg/ml (EC50 0.5–1 μg/ml)] and time (24&nda...
Source: FASEB Journal - October 1, 2015 Category: Biology Authors: Attur, M., Yang, Q., Shimada, K., Tachida, Y., Nagase, H., Mignatti, P., Statman, L., Palmer, G., Kirsch, T., Beier, F., Abramson, S. B. Tags: Research Communication Source Type: research
Influenza virus M2 targets cystic fibrosis transmembrane conductance regulator for lysosomal degradation during viral infection Research Communication
We sought to determine the mechanisms by which influenza infection of human epithelial cells decreases cystic fibrosis transmembrane conductance regulator (CFTR) expression and function. We infected human bronchial epithelial (NHBE) cells and murine nasal epithelial (MNE) cells with various strains of influenza A virus. Influenza infection significantly reduced CFTR short circuit currents (Isc) and protein levels at 8 hours postinfection. We then infected CFTR expressing human embryonic kidney (HEK)-293 cells (HEK-293 CFTRwt) with influenza virus encoding a green fluorescent protein (GFP) tag and performed whole-cell and c...
Source: FASEB Journal - June 30, 2015 Category: Biology Authors: Londino, J. D., Lazrak, A., Noah, J. W., Aggarwal, S., Bali, V., Woodworth, B. A., Bebok, Z., Matalon, S. Tags: Research Communication Source Type: research
Activated Kupffer cells inhibit insulin sensitivity in obese mice Research Communication
Obesity promotes insulin resistance associated with liver inflammation, elevated glucose production, and type 2 diabetes. Although insulin resistance is attenuated in genetic mouse models that suppress systemic inflammation, it is not clear whether local resident macrophages in liver, denoted Kupffer cells (KCs), directly contribute to this syndrome. We addressed this question by selectively silencing the expression of the master regulator of inflammation, NF-B, in KCs in obese mice. We used glucan-encapsulated small interfering RNA particles (GeRPs) that selectively silence gene expression in macrophages in vivo. Followin...
Source: FASEB Journal - June 30, 2015 Category: Biology Authors: Tencerova, M., Aouadi, M., Vangala, P., Nicoloro, S. M., Yawe, J. C., Cohen, J. L., Shen, Y., Garcia-Menendez, L., Pedersen, D. J., Gallagher-Dorval, K., Perugini, R. A., Gupta, O. T., Czech, M. P. Tags: Research Communication Source Type: research
Regulation of homologous recombinational repair by lamin B1 in radiation-induced DNA damage Research Communication
DNA double-strand breaks (DSBs) are the major lethal lesion induced by ionizing radiation (IR). RAD51-dependent homologous recombination (HR) is one of the most important pathways in DSB repair and genome integrity maintenance. However, the mechanism of HR regulation by RAD51 remains unclear. To understand the mechanism of RAD51-dependent HR, we searched for interacting partners of RAD51 by a proteomics analysis and identified lamin B1 in human cells. Lamins are nuclear lamina proteins that play important roles in the structural organization of the nucleus and the regulation of chromosome functions. Immunoblotting analyses...
Source: FASEB Journal - June 1, 2015 Category: Biology Authors: Liu, N.-A., Sun, J., Kono, K., Horikoshi, Y., Ikura, T., Tong, X., Haraguchi, T., Tashiro, S. Tags: Research Communication Source Type: research
Nuclear localization of the dystrophin-associated protein {alpha}-dystrobrevin through importin {alpha}2/{beta}1 is critical for interaction with the nuclear lamina/maintenance of nuclear integrity Research Communication
Although α-dystrobrevin (DB) is assembled into the dystrophin-associated protein complex, which is central to cytoskeletal organization, it has also been found in the nucleus. Here we delineate the nuclear import pathway responsible for nuclear targeting of α-DB for the first time, together with the importance of nuclear α-DB in determining nuclear morphology. We map key residues of the nuclear localization signal of α-DB within the zinc finger domain (ZZ) using various truncated versions of the protein, and site-directed mutagenesis. Pulldown, immunoprecipitation, and AlphaScreen assays showed that...
Source: FASEB Journal - April 30, 2015 Category: Biology Authors: Aguilar, A., Wagstaff, K. M., Suarez-Sanchez, R., Zinker, S., Jans, D. A., Cisneros, B. Tags: Research Communication Source Type: research
The endogenous zinc finger transcription factor, ZNF24, modulates the angiogenic potential of human microvascular endothelial cells Research Communication
We have previously identified a zinc finger transcription factor, ZNF24 (zinc finger protein 24), as a novel inhibitor of tumor angiogenesis and have demonstrated that ZNF24 exerts this effect by repressing the transcription of VEGF in breast cancer cells. Here we focused on the role of ZNF24 in modulating the angiogenic potential of the endothelial compartment. Knockdown of ZNF24 by siRNA in human primary microvascular endothelial cells (ECs) led to significantly decreased cell migration and invasion compared with control siRNA. ZNF24 knockdown consistently led to significantly impaired VEGF receptor 2 (VEGFR2) signaling ...
Source: FASEB Journal - April 1, 2015 Category: Biology Authors: Jia, D., Huang, L., Bischoff, J., Moses, M. A. Tags: Research Communication Source Type: research
Lysophosphatidate signaling stabilizes Nrf2 and increases the expression of genes involved in drug resistance and oxidative stress responses: implications for cancer treatment Research Communication
This study provides the first evidence that LPA increases antioxidant gene and multidrug-resistant transporter expression. Blocking this aspect of LPA signaling provides a novel strategy for improving chemotherapy.—Venkatraman, G., Benesch, M. G. K., Tang, X., Dewald, J., McMullen, T. P. W., Brindley, D. N. Lysophosphatidate signaling stabilizes Nrf2 and increases the expression of genes involved in drug resistance and oxidative stress responses: implications for cancer treatment.
Source: FASEB Journal - March 2, 2015 Category: Biology Authors: Venkatraman, G., Benesch, M. G. K., Tang, X., Dewald, J., McMullen, T. P. W., Brindley, D. N. Tags: Research Communication Source Type: research
Functional MMP-10 is required for efficient tissue repair after experimental hind limb ischemia Research Communication
We studied the role of matrix metalloproteinase-10 (MMP-10) during skeletal muscle repair after ischemia using a model of femoral artery excision in wild-type (WT) and MMP-10 deficient (Mmp10–/–) mice. Functional changes were analyzed by small animal positron emission tomography and tissue morphology by immunohistochemistry. Gene expression and protein analysis were used to study the molecular mechanisms governed by MMP-10 in hypoxia. Early after ischemia, MMP-10 deficiency resulted in delayed tissue reperfusion (10%, P < 0.01) and in increased necrosis (2-fold, P < 0.01), neutrophil (4-fold, P < 0.01)...
Source: FASEB Journal - March 2, 2015 Category: Biology Authors: Gomez-Rodriguez, V., Orbe, J., Martinez-Aguilar, E., Rodriguez, J. A., Fernandez-Alonso, L., Serneels, J., Bobadilla, M., Perez-Ruiz, A., Collantes, M., Mazzone, M., Paramo, J. A., Roncal, C. Tags: Research Communication Source Type: research
Adiponectin modulates focal adhesion disassembly in activated hepatic stellate cells: implication for reversing hepatic fibrosis Research Communications
Previous evidence indicates that adiponectin possesses antifibrogenic activity in inhibiting liver fibrosis. Therapeutic strategies, however, are limited by adiponectin quaternary structure and effective concentrations in circulation. Here we postulate a novel molecular mechanism, whereby adiponectin targets focal adhesion kinase (FAK) activity and disrupts key features of the fibrogenic response. Adiponectin-null (Ad–/–) mice and wild-type littermates were exposed to either saline or carbon tetrachloride (CCl4) for 6 wk. CCl4-gavaged mice were also injected with attenuated adenoviral adiponectin (Ad-Adn) or Ad...
Source: FASEB Journal - December 1, 2014 Category: Biology Authors: Kumar, P., Smith, T., Rahman, K., Mells, J. E., Thorn, N. E., Saxena, N. K., Anania, F. A. Tags: Research Communications Source Type: research
Melanoma upregulates ICAM-1 expression on endothelial cells through engagement of tumor CD44 with endothelial E-selectin and activation of a PKC{alpha}-p38-SP-1 pathway Research Communications
In conclusion, CD44/selectin binding signals ICAM-1 up-regulation on the EC surface through a PKCα–p38–SP-1 pathway, which further enhances melanoma cell adhesion to ECs during metastasis.—Zhang, P., Goodrich, C., Fu, C., Dong, C. Melanoma upregulates ICAM-1 expression on ECs through engagement of tumor CD44 with endothelial E-selectin and activation of a PKCα–p38–SP-1 pathway.
Source: FASEB Journal - October 30, 2014 Category: Biology Authors: Zhang, P., Goodrich, C., Fu, C., Dong, C. Tags: Research Communications Source Type: research
AMSH-mediated deubiquitination of Cx43 regulates internalization and degradation of gap junctions Research Communications
In this study, we demonstrate that Cx43 is modified with lysine 63-linked polyubiquitin chains and that these increase the interaction between Cx43 and AMSH. We also show that AMSH is recruited to GJ plaque sites at the plasma membrane, where it mediates the deubiquitination of Cx43. Using siRNA depletion or overexpression of a catalytically inactive mutant of AMSH, we show that by decreasing Cx43 deubiquitination, both the internalization and degradation rate of Cx43 are increased. Overall, these data strongly suggest that AMSH-mediated deubiquitination of Cx43 protects GJs from degradation.—Ribeiro-Rodrigues, T. M....
Source: FASEB Journal - October 30, 2014 Category: Biology Authors: Ribeiro-Rodrigues, T. M., Catarino, S., Marques, C., Ferreira, J. V., Martins-Marques, T., Pereira, P., Girao, H. Tags: Research Communications Source Type: research
Matrix metalloproteinase 9-mediated shedding of syndecan 4 in response to tumor necrosis factor {alpha}: a contributor to endothelial cell glycocalyx dysfunction Research Communications
The endothelial surface glycocalyx is a hydrated mesh in which proteoglycans are prominent. It is damaged in diseases associated with elevated levels of tumor necrosis factor α (TNF-α). We investigated the mechanism of TNF-α-induced disruption of the glomerular endothelial glycocalyx. We used conditionally immortalized human glomerular endothelial cells (GEnCs), quantitative PCR arrays, Western blotting, immunoprecipitation, immunofluorescence, and dot blots to examine the effects of TNF-α. TNF-α induced syndecan 4 (SDC4) mRNA up-regulation by 2.5-fold, whereas cell surface SDC4 and heparan su...
Source: FASEB Journal - October 30, 2014 Category: Biology Authors: Ramnath, R., Foster, R. R., Qiu, Y., Cope, G., Butler, M. J., Salmon, A. H., Mathieson, P. W., Coward, R. J., Welsh, G. I., Satchell, S. C. Tags: Research Communications Source Type: research
