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Total 656 results found since Jan 2013.

Nox4 redox regulation of PTP1B contributes to the proliferation and migration of glioblastoma cells by modulating tyrosine-phosphorylation of coronin-1C.
In this study, we demonstrated that silencing of Nox4 expression by Nox4-targeted siRNA suppressed cell growth and motility of glioblastoma U87 cells, indicating the involvement of Nox4. Furthermore, Nox4-derived ROS oxidized and inactivated protein tyrosine phosphatase (PTP):1B: PTP1B in its active form downregulates cell proliferation and migration. By affinity purification with the substrate-trapping mutant of PTP1B, tyrosine-phosphorylated coronin-1C was identified as a substrate of PTP1B. Its tyrosine phosphorylation level was suppressed by Nox4 inhibition, suggesting that tyrosine-phosphorylation of coronin-1C is reg...
Source: Free Radical Biology and Medicine - November 13, 2013 Category: Biology Authors: Mondol AS, Tonks NK, Kamata T Tags: Free Radic Biol Med Source Type: research

p38(MAPK) -regulated induction of p62 and NBR1 following PDT promotes autophagic clearance of ubiquitin-aggregates and reduces reactive oxygen species levels by supporting Nrf2-antioxidant signaling.
Abstract Emerging evidence indicate that oxidative stress instigates the formation of ubiquitin (Ub)-aggregates, substrates of autophagy, through a process requiring the ubiquitin binding adaptors p62/SQSTM1 and NBR1. Here, we have investigated the role of p62 and NBR1 in cell survival following hypericin-mediated photodynamic therapy (Hyp-PDT), a procedure known to incite robust ROS-based endoplasmic reticulum (ER) stress and autophagy pathways. We found that Hyp-PDT stimulated the formation of p62- and NBR1-associated Ub-aggregates in normal and cancer cells, which were ultimately removed by autophagy, through a...
Source: Free Radical Biology and Medicine - November 21, 2013 Category: Biology Authors: Rubio N, Verrax J, Dewaele M, Verfaillie T, Johansen T, Piette J, Agostinis P Tags: Free Radic Biol Med Source Type: research

ErbB3 binding protein-1 (Ebp1) controls proliferation and myogenic differentiation of muscle stem cells.
Abstract Satellite cells are resident stem cells of skeletal muscle, supplying myoblasts for postnatal muscle growth, hypertrophy and repair. Of the complex regulatory networks that control satellite cells, the EGF-family of ligands contributes. Here we investigated the role of ErbB3 binding protein-1 (Ebp1) in regulation of myogenic stem cell proliferation and differentiation. Ebp1 is a well-conserved DNA/RNA binding protein that is implicated in cell growth, apoptosis and differentiation in many cell types. Of the two main Ebp1 isoforms, only p48 was expressed in satellite cells and C2C12 myoblasts. While not pr...
Source: Developmental Biology - November 22, 2013 Category: Biology Authors: Figeac N, Serralbo O, Marcelle C, Zammit PS Tags: Dev Biol Source Type: research

Aldehyde dehydrogenase 3a1 protects airway epithelial cells from cigarette smoke-induced dna damage and cytotoxicity.
ALDEHYDE DEHYDROGENASE 3A1 PROTECTS AIRWAY EPITHELIAL CELLS FROM CIGARETTE SMOKE-INDUCED DNA DAMAGE AND CYTOTOXICITY. Free Radic Biol Med. 2013 Dec 4; Authors: Jang JH, Bruse S, Liu Y, Duffy V, Zhang C, Oyamada N, Randell S, Matsumoto A, Thompson DC, Lin Y, Vasiliou V, Tesfaigzi Y, Nyunoya T Abstract Aldehyde dehydrogenase 3A1 (ALDH3A1), an ALDH superfamily member, catalyzes the oxidation of reactive aldehydes, highly toxic components of cigarette smoke (CS). Even so, the role of ALDH3A1 in CS-induced cytotoxicity and DNA damage has not been examined. Among all of the ALDH superfamily members, ALDH3A1 mRNA...
Source: Free Radical Biology and Medicine - December 4, 2013 Category: Biology Authors: Jang JH, Bruse S, Liu Y, Duffy V, Zhang C, Oyamada N, Randell S, Matsumoto A, Thompson DC, Lin Y, Vasiliou V, Tesfaigzi Y, Nyunoya T Tags: Free Radic Biol Med Source Type: research

Vav1 as a Central Regulator of Invadopodia Assembly.
Abstract Invadopodia are protrusive structures used by tumor cells for degradation of the extracellular matrix to promote invasion [1]. Invadopodia formation and function are regulated by cytoskeletal-remodeling pathways and the oncogenic kinase Src. The guanine nucleotide exchange factor Vav1, which is an activator of Rho family GTPases, is ectopically expressed in many pancreatic cancers, where it promotes tumor cell survival and migration [2, 3]. We have now determined that Vav1 is also a potent regulator of matrix degradation by pancreatic tumor cells as depletion of Vav1 by siRNA-mediated knockdown inhibits t...
Source: Current Biology - December 11, 2013 Category: Biology Authors: Razidlo GL, Schroeder B, Chen J, Billadeau DD, McNiven MA Tags: Curr Biol Source Type: research

The Mitochondrial ROS regulator p66Shc controls PDGF-induced signaling and migration through PTP oxidation.
This study explores the contribution of p66Shc-induced ROS in PTP oxidation and growth factor receptor-induced signaling and migration through analyses of p66Shc KO fibroblasts and cells with siRNA-mediated p66Shc down-regulation. Analyses of PDGFβR phosphorylation in two independent cell systems demonstrated a decrease of PDGFβR phosphorylation after p66Shc deletion or down-regulation, which occurred in a partially site-selective and antioxidant-sensitive manner. Deletion of p66Shc also reduced PDGF-induced activation of downstream signaling of Erk, Akt, PLCγ-1 and FAK. Importantly, reduced levels of p66Shc lead to dec...
Source: Free Radical Biology and Medicine - December 27, 2013 Category: Biology Authors: Frijhoff J, Dagnell M, Augsten M, Beltrami E, Giorgio M, Ostman A Tags: Free Radic Biol Med Source Type: research

Systems analysis utilising pathway interactions identifies sonic hedgehog pathway as a primary biomarker and oncogenic target in hepatocellular carcinoma
The development and progression of cancer is associated with disruption of biological networks. Historically studies have identified sets of signature genes involved in events ultimately leading to the development of cancer. Identification of such sets does not indicate which biologic processes are oncogenic drivers and makes it difficult to identify key networks to target for interventions. Using a comprehensive, integrated computational approach, the authors identify the sonic hedgehog (SHH) pathway as the gene network that most significantly distinguishes tumour and tumour-adjacent samples in human hepatocellular carcin...
Source: IET Systems Biology - December 1, 2013 Category: Biology Source Type: research

Proopiomelanocortin gene delivery induces apoptosis in melanoma through NADPH oxidase 4-mediated ROS generation.
In this study, we characterize the involvement of hypoxia and reactive oxygen species (ROS) generation in the antineoplastic mechanism of proopiomelanocortin (POMC) gene delivery in a mouse B16-F10 melanoma model in vivo and in vitro. Histological analysis revealed increased TUNEL-positive cells and enhanced hypoxic activities in melanoma treated with adenovirus encoding POMC (Ad-POMC) but not control vector. Because the apoptotic cells were detected mainly in regions distant from blood vessels, it was hypothesized that POMC therapy might render melanoma cells vulnerable to hypoxic insult. Using a hypoxic chamber or cobalt...
Source: Free Radical Biology and Medicine - January 8, 2014 Category: Biology Authors: Liu GS, Wu JC, Tsai HE, Dusting GJ, Chan EC, Wu CS, Tai MH Tags: Free Radic Biol Med Source Type: research

Significance of the rapid increase in GSH levels in the protective response to cadmium exposure through phosphorylated Nrf2 signaling in Jurkat T-cells.
In this study, we initially determined that when human T cell-derived Jurkat cells were exposed to a low concentration of Cd, the glutathione (GSH) concentration rapidly increased via the transient nuclear accumulation of the transcription factor Nrf2. Therefore, we hypothesized that this increase in the GSH levels was a significant event that occurred in response to the Cd toxicity in the Jurkat T-cells. To test this hypothesis, the expression of Nrf2 in the cells was silenced using siRNA transfection. These restricted expression conditions demonstrated that the sensitivity of the Jurkat T-cells to Cd toxicity was signifi...
Source: Free Radical Biology and Medicine - January 14, 2014 Category: Biology Authors: Ogasawara Y, Takeda Y, Takayama H, Nishimoto S, Ichikawa K, Ueki M, Suzuki T, Ishii K Tags: Free Radic Biol Med Source Type: research

Glucosamine attenuates cigarette smoke-induced lung inflammation by inhibiting ROS-sensitive inflammatory signaling.
Abstract Cigarette smoking causes persistent lung inflammation that is mainly regulated by redox-sensitive pathways. We have reported that cigarette smoke (CS) activates a NADPH oxidase-dependent reactive oxygen species (ROS)-sensitive AMP-activated protein kinase (AMPK) signaling pathway leading to induction of lung inflammation. Glucosamine, a dietary supplement used to treat osteoarthritis, has antioxidant and anti-inflammatory properties. However, whether glucosamine has similar beneficial effects against CS-induced lung inflammation remains unclear. Using a murine model we show that chronic CS exposure for 4 ...
Source: Free Radical Biology and Medicine - January 28, 2014 Category: Biology Authors: Wu YL, Lin AH, Chen CH, Huang WC, Wang HY, Liu MH, Lee TS, Kou YR Tags: Free Radic Biol Med Source Type: research

NADPH oxidase 4 promotes cardiac microvascular angiogenesis following hypoxia/reoxygenation in vitro.
In conclusion, this study demonstrated a previous unrecognized protective role of Nox4, a ROS-generating enzyme and the major Nox isoform in CMECs, against H/R injury by inhibiting apoptosis, promoting migration and angiogenesis via a PHD2-dependent upregulation of HIF-1/VEGF proangiogenetic signaling. PMID: 24480752 [PubMed - as supplied by publisher]
Source: Free Radical Biology and Medicine - January 27, 2014 Category: Biology Authors: Wang J, Hong Z, Zeng C, Yu Q, Wang H Tags: Free Radic Biol Med Source Type: research

A Role for Myosin II in Mammalian Mitochondrial Fission.
Abstract Mitochondria are dynamic organelles, undergoing both fission and fusion regularly in interphase cells. Mitochondrial fission is thought to be part of a quality-control mechanism whereby damaged mitochondrial components are segregated from healthy components in an individual mitochondrion, followed by mitochondrial fission and degradation of the damaged daughter mitochondrion [1]. Fission also plays a role in apoptosis [2]. Defects in mitochondrial dynamics can lead to neurodegenerative diseases such as Alzheimer's disease [3]. Mitochondrial fission requires the dynamin GTPase Drp1, which assembles in a ri...
Source: Current Biology - January 28, 2014 Category: Biology Authors: Korobova F, Gauvin TJ, Higgs HN Tags: Curr Biol Source Type: research

Mathematical Model of a Telomerase Transcriptional Regulatory Network Developed by Cell-Based Screening: Analysis of Inhibitor Effects and Telomerase Expression Mechanisms
In this report, we used transfection screening to test interactions among 14 TERT regulatory transcription factors and their respective promoters in ovarian cancer cells. The results were used to generate a network model of TERT transcription and to implement a dynamic Boolean model whose steady states were analysed. Modelled effects of signal transduction inhibitors successfully predicted TERT repression by Src-family inhibitor SU6656 and lack of repression by ERK inhibitor FR180204, results confirmed by RT-QPCR analysis of endogenous TERT expression in treated cells. Modelled effects of GSK3 inhibitor 6-bromoindirubin-3â...
Source: PLoS Computational Biology - February 13, 2014 Category: Biology Authors: Alan E. Bilsland et al. Source Type: research

Role of Unfolded Protein Response in Affecting Osteoblast Differentiation Induced by Fluoride.
In conclusion, fluoride had dual effect on osteogenic action. The UPR possibly involved in the mechanism of osteoblasts differentiation induced by fluoride. PMID: 24522478 [PubMed - as supplied by publisher]
Source: Biological Trace Element Research - February 13, 2014 Category: Biology Authors: Li XN, Lv P, Sun Z, Li GS, Xu H Tags: Biol Trace Elem Res Source Type: research

Serotonin regulates innate immune responses of colon epithelial cells through NOX2-derived reactive oxygen species.
In this study, we examined the role and mechanism of action of 5-HT in inflammatory response of colon epithelial cells in vitro and in vivo. In colon epithelial cells (CCD 841, HT-29, Caco-2), direct application of 5-HT induced production of ROS and monocyte-epithelial adhesion, an initial event of inflammation, which were blocked not only by 5-HT receptor antagonists (tropisetron, RS39604, and SB269970), antioxidants (ascorbic acid, apocynin) and various inhibitors of NADPH oxidase (DPI), CREB (KG-501), and NF-κB (PDTC), but also by transfection with Nox2 siRNA. Nox2-derived production of ROS corresponded with the rapid ...
Source: Free Radical Biology and Medicine - February 10, 2014 Category: Biology Authors: Chandra Regmi S, Park SY, Kwang Ku S, Kim JA Tags: Free Radic Biol Med Source Type: research