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Total 33 results found since Jan 2013.

Intraluminal delivery of thrombospondin-2 small interfering RNA inhibits the vascular response to injury in a rat carotid balloon angioplasty model Research
In an effort to inhibit the response to vascular injury that leads to intimal hyperplasia, this study investigated the in vivo efficacy of intraluminal delivery of thrombospondin-2 (TSP-2) small interfering RNA (siRNA). Common carotid artery (CCA) balloon angioplasty injury was performed in rats. Immediately after denudation, CCA was transfected intraluminally (15 min) with one of the following: polyethylenimine (PEI)+TSP-2 siRNA, saline, PEI only, or PEI+control siRNA. CCA was analyzed at 24 h or 21 d by using quantitative real-time PCR and immunohistochemistry. TSP-2 gene and protein expression were significantly up-regu...
Source: FASEB Journal - January 2, 2017 Category: Biology Authors: Bodewes, T. C. F., Johnson, J. M., Auster, M., Huynh, C., Muralidharan, S., Contreras, M., LoGerfo, F. W., Pradhan-Nabzdyk, L. Tags: Research Source Type: research

RNA-induced silencing attenuates G protein-mediated calcium signals Research Communication
Phospholipase Cβ (PLCβ) is activated by G protein subunits in response to environmental stimuli to increase intracellular calcium. In cells, a significant portion of PLCβ is cytosolic, where it binds a protein complex required for efficient RNA-induced silencing called C3PO (component 3 promoter of RISC). Binding between C3PO and PLCβ raises the possibility that RNA silencing activity can affect the ability of PLCβ to mediate calcium signals. By use of human and rat neuronal cell lines (SK-N-SH and PC12), we show that overexpression of one of the main components of C3PO diminishes Ca2+ release in r...
Source: FASEB Journal - April 28, 2016 Category: Biology Authors: Philip, F., Sahu, S., Golebiewska, U., Scarlata, S. Tags: Research Communication 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

EphB2 contributes to human naive B-cell activation and is regulated by miR-185 Research Communications
In this study, the expression of EphB2 on B cells was tested by Western blot, and the roles of EphB2 in B-cell proliferation, cytokine secretion, and immunoglobulin (Ig) production were evaluated using EphB2 siRNA interference in human B cells from healthy volunteers. Our study revealed that EphB2 was distributed on naive B cells and was up-regulated on activated B cells. Moreover, B-cell proliferation (decreased by 22%, P<0.05), TNF-α secretion (decreased by 40%, P<0.01) and IgG production (decreased by 26%, P < 0.05) were depressed concordantly with the down-regulated EphB2 expression. Subsequently, we scr...
Source: FASEB Journal - July 30, 2014 Category: Biology Authors: Yu, M., Liang, W., Wen, S., Zhao, T., Zhu, M.-X., Li, H.-H., Long, Q., Wang, M., Cheng, X., Liao, Y.-H., Yuan, J. Tags: Research Communications Source Type: research

Opiorphin is a master regulator of the hypoxic response in corporal smooth muscle cells Research Communications
Men with sickle cell disease (SCD) risk developing priapism. Recognizing that SCD is a disease of hypoxia, we investigated the effect of hypoxia on gene expression in corporal smooth muscle (CSM) cells. Rat CSM cells in vitro were treated with CoCl2 or low oxygen tension to mimic hypoxia. Hypoxic conditions increased expression of genes previously associated with priapism in animal models. Variable coding sequence a1 (Vcsa1; the rat opiorphin homologue, sialorphin), hypoxia-inducible factor 1a (Hif-1a), and A2B adenosine receptor (a2br) were increased by 10-, 4-, and 6-fold, respectively, by treatment with CoCl2, whereas l...
Source: FASEB Journal - July 30, 2014 Category: Biology Authors: Fu, S., Tar, M. T., Melman, A., Davies, K. P. Tags: Research Communications 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

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

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

Lysophosphatidylethanolamine acyltransferase 1/membrane-bound O-acyltransferase 1 regulates morphology and function of P19C6 cell-derived neurons Research
In this study, we examined whether LPLATs are involved in neuronal differentiation using all-trans-retinoic acid (ATRA)–treated P19C6 cells. In these cells, mRNA levels of lysophosphatidylethanolamine acyltransferase (LPEAT)-1/membrane-bound O-acyltransferase (MBOAT)-1 were higher than those in undifferentiated cells. LPEAT enzymatic activity increased with 16:0- and 18:1-CoA as acyl donors. When LPEAT1/MBOAT1 was knocked down with small interfering RNA (siRNA), outgrowth of neurites and expression of neuronal markers decreased in ATRA-treated P19C6 cells. Voltage-dependent calcium channel activity was also suppresse...
Source: FASEB Journal - June 29, 2016 Category: Biology Authors: Tabe, S., Hikiji, H., Ariyoshi, W., Hashidate-Yoshida, T., Shindou, H., Okinaga, T., Shimizu, T., Tominaga, K., Nishihara, T. Tags: Research Source Type: research

Knockdown of DNA methyltransferase 3a alters gene expression and inhibits function of embryonic cardiomyocytes Research
We previously found that in utero caffeine exposure causes down-regulation of DNA methyltransferases (DNMTs) in embryonic heart and results in impaired cardiac function in adulthood. To assess the role of DNMTs in these events, we investigated the effects of reduced DNMT expression on embryonic cardiomyocytes. siRNAs were used to knock down individual DNMT expression in primary cultures of mouse embryonic cardiomyocytes. Immunofluorescence staining was conducted to evaluate cell morphology. A video-based imaging assay and multielectrode array were used to assess cardiomyocyte contractility and electrophysiology, respective...
Source: FASEB Journal - August 31, 2016 Category: Biology Authors: Fang, X., Poulsen, R. R., Wang-Hu, J., Shi, O., Calvo, N. S., Simmons, C. S., Rivkees, S. A., Wendler, C. C. Tags: Research Source Type: research

Cooperation of Musashi-2, Numb, MDM2, and P53 in drug resistance and malignant biology of pancreatic cancer Research
Our earlier work showed that Musashi (MSI)-2 promoted the development of pancreatic cancer (PC) by down-regulating Numb, which prevented murine double-minute (MDM)-2–mediated p53 ubiquitin degradation. Thus, we investigate the relationship among MSI2, Numb, MDM2, and p53 in PC in vitro and in vivo, an association that has not been reported to our knowledge. MSI2 had no relationship with mutant p53 (mtp53) and wild-type p53 (wtp53) in normal PC cells. However, in response to gemcitabine or cisplatin treatment, MSI2 silencing simultaneously down-regulated MDM2 and up-regulated Numb and wtp53 protein levels. Moreover, t...
Source: FASEB Journal - June 1, 2017 Category: Biology Authors: Sheng, W., Dong, M., Chen, C., Wang, Z., Li, Y., Wang, K., Li, Y., Zhou, J. Tags: Research Source Type: research

Role of HSP60 (HSPD1) in diabetes-induced renal tubular dysfunction: regulation of intracellular protein aggregation, ATP production, and oxidative stress Research
Because underlying mechanisms of diabetic nephropathy/tubulopathy remained poorly understood, we aimed to define a key protein involving in hyperglycemia-induced renal tubular dysfunction. All altered renal proteins identified from previous large-scale proteome studies were subjected to global protein network analysis, which revealed heat shock protein 60 (HSP60, also known as HSPD1) as the central node of protein–protein interactions. Functional validation was performed using small interfering RNA (siRNA) to knock down HSP60 (siHSP60). At 48 h after exposure to high glucose (HG) (25 mM), Madin-Darby canine kidney (M...
Source: FASEB Journal - May 1, 2017 Category: Biology Authors: Aluksanasuwan, S., Sueksakit, K., Fong-ngern, K., Thongboonkerd, V. Tags: Research 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

{beta}-Arrestin-1 mediates thyrotropin-enhanced osteoblast differentiation Research Communications
Thyrotropin (TSH) activation of the TSH receptor (TSHR), a 7-transmembrane-spanning receptor (7TMR), may have osteoprotective properties by direct effects on bone. TSHR activation by TSH phosphorylates protein kinases AKT1, p38α, and ERK1/2 in some cells. We found TSH-induced phosphorylation of these kinases in 2 cell lines engineered to express TSHRs, human embryonic kidney HEK-TSHR cells and human osteoblastic U2OS-TSHR cells. In U2OS-TSHR cells, TSH up-regulated pAKT1 (7.1±0.5-fold), p38α (2.9±0.4-fold), and pERK1/2 (3.1±0.2-fold), whereas small molecule TSHR agonist C2 had no or little ...
Source: FASEB Journal - July 30, 2014 Category: Biology Authors: Boutin, A., Eliseeva, E., Gershengorn, M. C., Neumann, S. Tags: Research Communications Source Type: research