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Total 33 results found since Jan 2013.
A PP2A-mediated feedback mechanism controls Ca2+-dependent NO synthesis under physiological oxygen Research
Intracellular O2 is a key regulator of NO signaling, yet most in vitro studies are conducted in atmospheric O2 levels, hyperoxic with respect to the physiologic milieu. We investigated NO signaling in endothelial cells cultured in physiologic (5%) O2 and stimulated with histamine or shear stress. Culture of cells in 5% O2 (>5 d) decreased histamine- but not shear stress–stimulated endothelial (e)NOS activity. Unlike cells adapted to a hypoxic environment (1% O2), those cultured in 5% O2 still mobilized sufficient Ca2+ to activate AMPK. Enhanced expression and membrane targeting of PP2A-C was observed in 5% O2, res...
Source: FASEB Journal - November 30, 2017 Category: Biology Authors: Keeley, T. P., Siow, R. C. M., Jacob, R., Mann, G. E. Tags: Research Source Type: research
LEF1-mediated MMP13 gene expression is repressed by SIRT1 in human chondrocytes Research
In this study, we assessed the role of SIRT1 in LEF1-mediated MMP13 gene expression in human OA chondrocytes. Results showed that MMP13 protein levels and enzymatic activity decreased significantly during SIRT1 overexpression or activation by resveratrol. Conversely, MMP13 gene expression was reduced in chondrocytes transfected with SIRT1 siRNA or treated with nicotinamide (NAM), a sirtuin inhibitor. Chondrocytes challenged with IL-1β, a cytokine involved in OA pathogenesis, enhanced LEF1 protein levels and gene expression, resulting in increased MMP13 gene expression; however, overexpression of SIRT1 during IL-1&beta...
Source: FASEB Journal - June 29, 2017 Category: Biology Authors: Elayyan, J., Lee, E.-J., Gabay, O., Smith, C. A., Qiq, O., Reich, E., Mobasheri, A., Henrotin, Y., Kimber, S. J., Dvir-Ginzberg, M. 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
Osteogenesis requires FAK-dependent collagen synthesis by fibroblasts and osteoblasts Research
Focal adhesion kinase (FAK) is critical in adhesion-dependent signaling, but its role in osteogenesis in vivo is ill defined. We deleted Fak in fibroblasts and osteoblasts in Floxed-Fak mice bred with those expressing Cre-recombinase driven by 3.6-kb α1(I)-collagen promoter. Compared with wild-type (WT), conditional FAK-knockout (CFKO) mice were shorter (2-fold; P < 0.0001) and had crooked, shorter tails (50%; P < 0.0001). Microcomputed tomography analysis showed reduced bone volume (4-fold in tails; P < 0.0001; 2-fold in mandibles; P < 0.0001), whereas bone surface area/bone volume increased (3-fold in t...
Source: FASEB Journal - February 27, 2017 Category: Biology Authors: Rajshankar, D., Wang, Y., McCulloch, C. A. Tags: Research Source Type: research
Loss-of-function screens of druggable targetome against cancer stem-like cells Research
In this study, small interfering RNA (siRNA)-based screening of ~4800 druggable genes in 3-dimensional CSLC cultures in comparison to 2-dimensional bulk cultures of U87 glioma cells revealed 3 groups of genes essential for the following: survival of the CSLC population only, bulk-cultured population only, or both populations. While diverse biologic processes were associated with siRNAs reducing the bulk-cultured population, CSLC-eliminating siRNAs were enriched in a few functional categories, such as lipid metabolism, protein metabolism, and gene expression. Interestingly, siRNAs that selectively reduced CSLC only were fou...
Source: FASEB Journal - January 31, 2017 Category: Biology Authors: Song, M., Lee, H., Nam, M.-H., Jeong, E., Kim, S., Hong, Y., Kim, N., Yim, H. Y., Yoo, Y.-J., Kim, J. S., Kim, J.-S., Cho, Y.-Y., Mills, G. B., Kim, W.-Y., Yoon, S. Tags: Research Source Type: research
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
Insulin receptor substrate-1 time-dependently regulates bone formation by controlling collagen I{alpha}2 expression via miR-342 Research
Insulin promotes bone formation via a well-studied canonical signaling pathway. An adapter in this pathway, insulin-receptor substrate (IRS)-1, has been implicated in the diabetic osteopathy provoked by impaired insulin signaling. To further investigate IRS-1’s role in the bone metabolism, we generated Irs-1-deficient Irs-1smla/smla mice. These null mice developed a spontaneous mutation that led to an increase in trabecular thickness (Tb.Th) in 12-mo-old, but not in 2-mo-old mice. Analyses of the bone marrow stromal cells (BMSCs) from these mice revealed their differential expression of osteogenesis-related genes and...
Source: FASEB Journal - November 29, 2016 Category: Biology Authors: Guo, Y., Tang, C.-Y., Man, X.-F., Tang, H.-N., Tang, J., Wang, F., Zhou, C.-L., Tan, S.-W., Feng, Y.-Z., Zhou, H.-D. Tags: Research Source Type: research
Novel role for p56/Lck in regulation of endothelial cell survival and angiogenesis Research
This study assessed the role of tyrosine–protein kinase Lck (p56/Lck) in this pathway. We analyzed early events leading to apoptosis of human endothelial cells exposed to HKa. The role of p56/Lck was investigated using short interfering (si) RNA knockdown and lentivirus expression in assays of endothelial tube formation, sprouting of neovessels from murine aorta, and angiogenesis in Matrigel plugs. HKa stimulated expression and phosphorylation of p56/Lck. siRNA knockdown of p56/Lck promoted endothelial proliferation and blocked HKa-induced apoptosis and activation of p53, Bax, and Bak. Lentivirus expression of p56/Lc...
Source: FASEB Journal - October 2, 2016 Category: Biology Authors: Betapudi, V., Shukla, M., Alluri, R., Merkulov, S., McCrae, K. R. Tags: Research Source Type: research
Tetraspanin-2 promotes glucotoxic apoptosis by regulating the JNK/{beta}-catenin signaling pathway in human pancreatic {beta} cells Research
Diabetes mellitus is a complex and heterogeneous disease, which has β-cell dysfunction at its core. Glucotoxicity affects pancreatic islets, causing β-cell apoptosis. However, the role of JNK/β-catenin signaling in glucotoxic β-cell apoptosis is not well understood. Recently, we identified tetraspanin-2 (TSPAN2) protein as a proapoptotic β-cell factor induced by glucose, suggesting that TSPAN2 might contribute to pancreatic β-cell glucotoxicity. To investigate the effects of glucose concentration on TSPAN2 expression and apoptosis, we used reverted immortalized RNAKT-15 human pancreatic β...
Source: FASEB Journal - August 31, 2016 Category: Biology Authors: Hwang, I.-H., Park, J., Kim, J. M., Kim, S. I., Choi, J.-S., Lee, K.-B., Yun, S. H., Lee, M.-G., Park, S. J., Jang, I.-S. 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
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
{mu}-Crystallin controls muscle function through thyroid hormone action Research Communication
In this study, Crym was preferentially expressed in skeletal muscle throughout the body. Crym-knockout mice exhibited a significant hypertrophy of fast-twitch glycolytic type IIb fibers, causing an increase in grip strength and high intensity running ability in Crym-null mice. Genetic inactivation of Crym or blockade of Crym by siRNA-mediated knockdown up-regulated the gene expression of fast-glycolytic contractile fibers in satellite cell-derived myotubes in vitro. These alterations in Crym-inactivated muscle were rescued by inhibition of thyroid hormone, even though Crym is a positive regulator of thyroid hormone action ...
Source: FASEB Journal - April 28, 2016 Category: Biology Authors: Seko, D., Ogawa, S., Li, T.-S., Taimura, A., Ono, Y. Tags: Research Communication 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
Combination of small RNAs for skeletal muscle regeneration Research Communication
In this study, we used myostatin small interfering (si)RNA (siGDF-8), a major inhibitory factor in the development and postnatal regeneration of skeletal muscle and muscle-specific microRNAs (miR-1 and -206) to further accelerate muscle regeneration. This combination of 3 small RNAs significantly improved the gene expression of myogenic regulatory factors in vitro, suggesting myogenic activation. Moreover, cell proliferation and myotube formation improved without compromising each other, which indicates the myogenic potential of this combination of small RNAs. The recovery of chemically injured tibialis anterior muscles in...
Source: FASEB Journal - March 1, 2016 Category: Biology Authors: Kim, N., Yoo, J. J., Atala, A., Lee, S. J. Tags: Research Communication Source Type: research
