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Total 656 results found since Jan 2013.

The transcription factor Nrf2 promotes survival by enhancing the expression of uncoupling protein 3 under conditions of oxidative stress.
In conclusion, we have identified a novel regulatory process induced by an oxidative insult whereby the expression of the mitochondrial protein UCP3 is driven by the Nrf2 transcription factor, which decreases ROS production and prevents cell death. PMID: 23597505 [PubMed - as supplied by publisher]
Source: Free Radical Biology and Medicine - April 16, 2013 Category: Biology Authors: Anedda A, López-Bernardo E, Acosta-Iborra B, Saadeh Suleiman M, Landázuri MO, Cadenas S Tags: Free Radic Biol Med Source Type: research

The role of the Nrf2-mediated defense system in corneal epithelial wound healing.
In this study, we investigated the role of the Nrf2-mediated defense system in corneal epithelial wound healing by using Nrf2-knockout (KO) mice. Nrf2 was expressed in the corneal epithelium of wild-type (WT) mice, but not in KO mice. Observation of wounds after 24h of healing revealed that healing of the corneal epithelium was significantly delayed in the Nrf2 KO mice, whereas Nrf2 was activated in the corneal epithelium of WT mice. Ki-67 staining revealed that the number of Ki-67-positive proliferating cells was significantly lower in the Nrf2 KO mice than in the WT mice at 24-36h after injury; however, these numbers wer...
Source: Free Radical Biology and Medicine - April 12, 2013 Category: Biology Authors: Hayashi R, Himori N, Taguchi K, Ishikawa Y, Uesugi K, Ito M, Duncan T, Tsujikawa M, Nakazawa T, Yamamoto M, Nishida K Tags: Free Radic Biol Med Source Type: research

Homocysteine alters the osteoprotegerin/RANKL system in the osteoblast to promote bone loss: pivotal role of the redox regulator forkhead O1.
In this study we determined the molecular mechanisms of how homocysteine differentially affects receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) synthesis in the bone. The results showed that oxidative stress induced by homocysteine deranges insulin-sensitive FOXO1 and MAP kinase signaling cascades to decrease OPG and increase RANKL synthesis in osteoblast cultures. We observed that downregulation of insulin/FOXO1 and p38 MAP kinase signaling mechanisms due to phosphorylation of protein phosphatase 2A (PP2A) was the key event that inhibited OPG synthesis in homocysteine-treated osteoblast c...
Source: Free Radical Biology and Medicine - March 15, 2013 Category: Biology Authors: Vijayan V, Khandelwal M, Manglani K, Singh RR, Gupta S, Surolia A Tags: Free Radic Biol Med Source Type: research

Dimerumic acid attenuates receptor for advanced glycation endproducts signal to inhibit inflammation and diabetes mediated by Nrf2 activation and promotes methylglyoxal metabolism into d-lactic acid.
This study was designed to evaluate the effects of dimerumic acid (DMA) on receptor for advanced glycation endproducts (RAGE) signal activation and THP-1 monocyte inflammation treated with S100b, a specific ligand of RAGE. We found that DMA inhibited inflammatory cytokine production via upregulation of nuclear factor-erythroid 2-related factor 2 (Nrf2) and alleviated oxidative stress through attenuation of p47phox translocation to the membrane of S100b-treated THP-1 monocytes. We found that DMA activated Nrf2 mediated by the p38 kinase pathway in THP-1 monocytes. However, anti-inflammatory activity of DMA was attenuated by...
Source: Free Radical Biology and Medicine - May 23, 2013 Category: Biology Authors: Lee BH, Hsu WH, Hsu YW, Pan TM Tags: Free Radic Biol Med Source Type: research

Aberrant Wnt signalling and cellular over-proliferation in a novel mouse model of Meckel-Gruber syndrome.
Abstract Meckel-Gruber syndrome (MKS) is an embryonic lethal ciliopathy resulting from mutations in genes encoding proteins localising to the primary cilium. Mutations in the basal body protein MKS1 account for 7% of cases of MKS. The condition affects the development of multiple organs, including brain, kidney and skeleton. Here we present a novel Mks1(tm1a(EUCOMM)Wtsi) knockout mouse which accurately recapitulates the human condition, consistently developing pre-axial polydactyly, complex posterior fossa defects (including the Dandy-Walker malformation), and renal cystic dysplasia. TOPFlash Wnt reporter assays i...
Source: Developmental Biology - May 1, 2013 Category: Biology Authors: Wheway G, Abdelhamed Z, Natarajan S, Toomes C, Inglehearn C, Johnson CA Tags: Dev Biol Source Type: research

Pitx genes are redeployed in adult myogenesis where they can act to promote myogenic differentiation in muscle satellite cells.
Abstract Skeletal muscle retains a resident stem cell population called satellite cells. Although mitotically quiescent in mature muscle, satellite cells can be activated to produce myoblast progeny to generate myonuclei for skeletal muscle homoeostasis, hypertrophy and repair. Regulation of satellite cell function in adult requires redeployment of many of the regulatory networks fundamental to developmental myogenesis. Involved in such control of muscle stem cell fate in embryos are members of the Pitx gene family of bicoid-class homeodomain proteins. Here, we investigated the expression and function of all three...
Source: Developmental Biology - May 1, 2013 Category: Biology Authors: Knopp P, Figeac N, Fortier M, Moyle L, Zammit PS Tags: Dev Biol Source Type: research

Effects of Zinc Transporter on Differentiation of Bone Marrow Mesenchymal Stem Cells to Osteoblasts.
Abstract The differentiation of bone marrow mesenchymal stem cells (MSCs) into osteoblasts is a crucial step during bone formation. However, the exact mechanisms regulating the early stages of osteogenic differentiation remain unknown. In the present study, we found that ZnT7, a member of the zinc transporter family SLC30A(ZnTs), was downregulated during dexamethasone-induced differentiation of rat MSCs into osteoblasts. Dexamethasone treatment resulted in significantly lower levels of ZnT7 compared with cocultured cells without dexamethasone. Differentiation was evaluated by measuring alkaline phosphatase (ALP) a...
Source: Biological Trace Element Research - June 18, 2013 Category: Biology Authors: Liu Y, Yan F, Yang WL, Lu XF, Wang WB Tags: Biol Trace Elem Res Source Type: research

Structural insights into the arms race between host and virus along RNA silencing pathways in Arabidopsis thaliana
ABSTRACT RNA silencing refers to a conserved sequence‐specific gene‐regulation mechanism mediated by small RNA molecules. In plants, microRNA (miRNA) and small interfering RNA (siRNA) represent two major types of small RNA molecules which play pivotal roles in plant developmental control and antiviral defences. To escape these plant defences, plant viruses have encoded a vast array of viral suppressors of RNA silencing (VSRs) to attack the host antiviral silencing pathway by interfering with small RNA processing, RNA‐induced silencing complex (RISC) assembly, viral mRNA cleavage etc. Transgenic plants expressing dist...
Source: Biological Reviews - August 1, 2013 Category: Biology Authors: Wei Guo, Jia Yee Liew, Y. Adam Yuan Tags: Original Article Source Type: research

Target Inhibition Networks: Predicting Selective Combinations of Druggable Targets to Block Cancer Survival Pathways
by Jing Tang, Leena Karhinen, Tao Xu, Agnieszka Szwajda, Bhagwan Yadav, Krister Wennerberg, Tero Aittokallio A recent trend in drug development is to identify drug combinations or multi-target agents that effectively modify multiple nodes of disease-associated networks. Such polypharmacological effects may reduce the risk of emerging drug resistance by means of attacking the disease networks through synergistic and synthetic lethal interactions. However, due to the exponentially increasing number of potential drug and target combinations, systematic approaches are needed for prioritizing the most potent multi-target alter...
Source: PLoS Computational Biology - September 12, 2013 Category: Biology Authors: Jing Tang et al. Source Type: research

Structural insights into the arms race between host and virus along RNA silencing pathways in Arabidopsis thaliana.
Abstract RNA silencing refers to a conserved sequence-specific gene-regulation mechanism mediated by small RNA molecules. In plants, microRNA (miRNA) and small interfering RNA (siRNA) represent two major types of small RNA molecules which play pivotal roles in plant developmental control and antiviral defences. To escape these plant defences, plant viruses have encoded a vast array of viral suppressors of RNA silencing (VSRs) to attack the host antiviral silencing pathway by interfering with small RNA processing, RNA-induced silencing complex (RISC) assembly, viral mRNA cleavage etc. Transgenic plants expressing d...
Source: Biological Reviews of the Cambridge Philosophical Society - September 4, 2013 Category: Biology Authors: Guo W, Liew JY, Yuan YA Tags: Biol Rev Camb Philos Soc Source Type: research

Mechanism of protein decarbonylation.
Abstract Ligand/receptor-stimulation of cells promotes protein carbonylation that is followed by the decarbonylation process, which might involve thiol-dependent reduction (Wong et al., Circ. Res. 102 301-318, 2008). The present study further investigated the properties of this protein decarbonylation mechanism. We found that the thiol-mediated reduction of protein carbonyls is dependent on heat-labile biologic components. Cysteine and glutathione were found to be efficient substrates for decarbonylation. Thiols decreased the protein carbonyl content, as detected by 2,4-dinitrophenylhydrazine, but not the levels o...
Source: Free Radical Biology and Medicine - September 14, 2013 Category: Biology Authors: Wong CM, Marcocci L, Das D, Wang X, Luo H, Zungu-Edmondson M, Suzuki YJ Tags: Free Radic Biol Med Source Type: research

A functional link between heme oxygenase-1 and tristetraprolin in the anti-inflammatory effects of nicotine.
In this study, we sought to determine whether HO-1 associates with TTP to mediate the anti-inflammatory effects of nicotine. Inhibition of HO-1 activity or HO-1 expression attenuated the effects of nicotine on STAT3 activation, TTP induction, and TNF-α production in LPS-treated macrophages. Induction of HO-1 expression increased the level of TTP in the absence of nicotine. In a LPS-induced endotoxemia model, HO-1 deficiency blocked the effects of nicotine on the STAT3 phosphorylation, TTP induction and LPS-induced TNF-α production in the liver. Downregulation of STAT3 by siRNA attenuated the effect of nicotine on TTP exp...
Source: Free Radical Biology and Medicine - October 2, 2013 Category: Biology Authors: Uddin MJ, Joe Y, Zheng M, Blackshear PJ, Ryter SW, Park JW, Chung HT Tags: Free Radic Biol Med Source Type: research

Α-synuclein and mitochondrial bioenergetics regulate tetrahydrobiopterin levels in a human dopaminergic model of PD.
Abstract Parkinson's disease (PD) is a multi-factorial disease resulting in preferential death of the dopaminergic neurons in the substantia nigra. Studies of PD-linked genes and toxin-induced models of PD have implicated mitochondrial dysfunction, oxidative stress and the misfolding and aggregation of α-synuclein (α-syn) as key factors in disease initiation and progression. Many of these features of PD may be modelled in cells or animal models using the neurotoxin 1-methyl-4-phenylpyridinium (MPP+). Reducing oxidative stress and NOS activity have been shown to be protective in cell or animal models of MPP+ toxi...
Source: Free Radical Biology and Medicine - October 19, 2013 Category: Biology Authors: Ryan BJ, Lourenço-Venda L, Crabtree MJ, Hale AB, Channon KM, Wade-Martins R Tags: Free Radic Biol Med Source Type: research

The Human Constitutive Androstane Receptor Promotes the Differentiation and Maturation of Hepatic-like Cells.
Abstract Expression of the constitutive androstane receptor (CAR, NR1I3) is enriched in the mature mammalian liver and increasingly recognized for its prominent role in regulating a myriad of processes including biotransformation, chemical transport, energy metabolism and lipid homeostasis. Previously, we demonstrated that CAR levels were markedly enhanced during the differentiation of hepatic-like cells derived from hESCs, prompting the hypothesis that CAR contributes a key functional role in directing human hepatogenesis. Here we demonstrate that over-expression of CAR in human embryonic stem cells (ESCs), trans...
Source: Developmental Biology - October 18, 2013 Category: Biology Authors: Chen F, Zamule SM, Coslo DM, Chen T, Omiecinski CJ Tags: Dev Biol Source Type: research

Ferritin heavy chain as main mediator of preventive effect of metformin on mitochondrial damage induced by doxorubicin in cardiomyocyte.
In conclusion, these results deepen our knowledge of the protective action of MET against DOX-induced cardiotoxicity and suggest that therapeutic strategies based on FHC modulation could protect cardiomyocytes from the mitochondrial damage induced by DOX by restoring iron homeostasis. PMID: 24231192 [PubMed - as supplied by publisher]
Source: Free Radical Biology and Medicine - November 11, 2013 Category: Biology Authors: Asensio-Lopez MC, Sanchez-Mas J, Pascual-Figal DA, de Torre C, Valdes M, Lax A Tags: Free Radic Biol Med Source Type: research