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[PMID]: 25392529
[Au] Autor:Ramon S; Baker SF; Sahler JM; Kim N; Feldsott EA; Serhan CN; Martínez-Sobrido L; Topham DJ; Phipps RP
[Ad] Address:Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642; Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical Schoo...
[Ti] Title:The Specialized Proresolving Mediator 17-HDHA Enhances the Antibody-Mediated Immune Response against Influenza Virus: A New Class of Adjuvant?
[So] Source:J Immunol;193(12):6031-40, 2014 Dec 15.
[Is] ISSN:1550-6606
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Influenza viruses remain a critical global health concern. More efficacious vaccines are needed to protect against influenza virus, yet few adjuvants are approved for routine use. Specialized proresolving mediators (SPMs) are powerful endogenous bioactive regulators of inflammation, with great clinical translational properties. In this study, we investigated the ability of the SPM 17-HDHA to enhance the adaptive immune response using an OVA immunization model and a preclinical influenza vaccination mouse model. Our findings revealed that mice immunized with OVA plus 17-HDHA or with H1N1-derived HA protein plus 17-HDHA increased Ag-specific Ab titers. 17-HDHA increased the number of Ab-secreting cells in vitro and the number of HA-specific Ab-secreting cells present in the bone marrow. Importantly, the 17-HDHA-mediated increased Ab production was more protective against live pH1N1 influenza infection in mice. To our knowledge, this is the first report on the biological effects of ω-3-derived SPMs on the humoral immune response. These findings illustrate a previously unknown biological link between proresolution signals and the adaptive immune system. Furthermore, this work has important implications for the understanding of B cell biology, as well as the development of new potential vaccine adjuvants.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1412
[Cu] Class update date: 141206
[Lr] Last revision date:141206
[Js] Journal subset:AIM; IM
[St] Status:In-Data-Review
[do] DOI:10.4049/jimmunol.1302795

  2 / 314116 MEDLINE  
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[PMID]: 25378596
[Au] Autor:Ma Y; Bramwell KK; Lochhead RB; Paquette JK; Zachary JF; Weis JH; Teuscher C; Weis JJ
[Ad] Address:Division of Microbiology and Immunology, Department of Pathology, University of Utah, Salt Lake City, UT 84112;...
[Ti] Title:Borrelia burgdorferi Arthritis-Associated Locus Bbaa1 Regulates Lyme Arthritis and K/B×N Serum Transfer Arthritis through Intrinsic Control of Type I IFN Production.
[So] Source:J Immunol;193(12):6050-60, 2014 Dec 15.
[Is] ISSN:1550-6606
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Localized upregulation of type I IFN was previously implicated in development of Borrelia burgdorferi-induced arthritis in C3H mice, and was remarkable due to its absence in the mildly arthritic C57BL/6 (B6) mice. Independently, forward genetics analysis identified a quantitative trait locus on Chr4, termed B. burgdorferi-associated locus 1 (Bbaa1), that regulates Lyme arthritis severity and includes the 15 type I IFN genes. Involvement of Bbaa1 in arthritis development was confirmed in B6 mice congenic for the C3H allele of Bbaa1 (B6.C3-Bbaa1), which developed more severe Lyme arthritis and K/B×N model of rheumatoid arthritis (RA) than did parental B6 mice. Administration of a type I IFN receptor blocking mAb reduced the severity of both Lyme arthritis and RA in B6.C3-Bbaa1 mice, formally linking genetic elements within Bbaa1 to pathological production of type I IFN. Bone marrow-derived macrophages from Bbaa1 congenic mice implicated this locus as a regulator of type I IFN induction and downstream target gene expression. Bbaa1-mediated regulation of IFN-inducible genes was upstream of IFN receptor-dependent amplification; however, the overall magnitude of the response was dependent on autocrine/paracrine responses to IFN-ß. In addition, the Bbaa1 locus modulated the functional phenotype ascribed to bone marrow-derived macrophages: the B6 allele promoted expression of M2 markers, whereas the C3H allele promoted induction of M1 responses. This report identifies a genetic locus physically and functionally linked to type I IFN that contributes to the pathogenesis of both Lyme and RA.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1412
[Cu] Class update date: 141206
[Lr] Last revision date:141206
[Js] Journal subset:AIM; IM
[St] Status:In-Data-Review
[do] DOI:10.4049/jimmunol.1401746

  3 / 314116 MEDLINE  
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[PMID]: 25248763
[Au] Autor:Miller MR; Mandell JB; Beatty KM; Harvey SA; Rizzo MJ; Previte DM; Thorne SH; McKenna KC
[Ad] Address:Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania....
[Ti] Title:Splenectomy Promotes Indirect Elimination of Intraocular Tumors by CD8+ T Cells That Is Associated with IFNγ- and Fas/FasL-Dependent Activation of Intratumoral Macrophages.
[So] Source:Cancer Immunol Res;2(12):1175-85, 2014 Dec.
[Is] ISSN:2326-6074
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Ocular immune privilege (IP) limits the immune surveillance of intraocular tumors as certain immunogenic tumor cell lines (P815, E.G7-OVA) that are rejected when transplanted in the skin grow progressively when placed in the anterior chamber of the eye. As splenectomy (SPLNX) is known to terminate ocular IP, we characterized the immune mechanisms responsible for rejection of intraocular tumors in SPLNX mice as a first step toward identifying how to restore tumoricidal activity within the eye. CD8(+) T cells, IFNγ, and FasL, but not perforin, or TNFα were required for the elimination of intraocular E.G7-OVA tumors that culminated in destruction of the eye (ocular phthisis). IFNγ and FasL did not target tumor cells directly as the majority of SPLNX IFNγR1(-/-) mice and Fas-defective lpr mice failed to eliminate intraocular E.G7-OVA tumors that expressed Fas and IFNγR1. Bone marrow chimeras revealed that IFNγR1 and Fas expression on immune cells was most critical for rejection, and SPLNX increased the frequency of activated macrophages (MÏ•) within intraocular tumors in an IFNγ- and Fas/FasL-dependent manner, suggesting an immune cell target of IFNγ and Fas. As depletion of MÏ•s limited CD8 T cell-mediated rejection of intraocular tumors in SPLNX mice, our data support a model in which IFNγ- and Fas/FasL-dependent activation of intratumoral MÏ•s by CD8(+) T cells promotes severe intraocular inflammation that indirectly eliminates intraocular tumors by inducing phthisis, and suggests that immunosuppressive mechanisms that maintain ocular IP interfere with the interaction between CD8(+) T cells and MÏ•s to limit the immunosurveillance of intraocular tumors. Cancer Immunol Res; 2(12); 1175-85. ©2014 AACR.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1412
[Cu] Class update date: 141206
[Lr] Last revision date:141206
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1158/2326-6066.CIR-14-0093-T

  4 / 314116 MEDLINE  
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[PMID]: 25473215
[Au] Autor:Jeong HS; Lee HK; Tark KC; Lew DH; Koh YW; Kim CH; Seo IS
[Ad] Address:Department of Plastic & Reconstructive Surgery, Kangnam Sacred Heart Hospital, Hallym University Medical Center, Halllym University College of Medicine, Seoul, Korea. ; Department of Plastic and Reconstructive Surgery, Institute for Human Tissue Restoration, Yonsei University College of Medicine...
[Ti] Title:Effect of Endogenous Bone Marrow Derived Stem Cells Induced by AMD-3100 on Expanded Ischemic Flap.
[So] Source:J Korean Med Sci;29 Suppl 3:S237-48, 2014 Nov.
[Is] ISSN:1598-6357
[Cp] Country of publication:Korea (South)
[La] Language:eng
[Ab] Abstract:The purpose of this study was to devise an expanded ischemic flap model and to investigate the role of AMD-3100 (Plerixafor, chemokine receptor 4 inhibitor) in this model by confirming its effect on mobilization of stem cells from the bone marrow. Male Sprague-Dawley rats were used as an animal research model. The mobilization of stem cells from the bone marrow was confirmed in the AMD-3100-treated group. The fractions of endothelial progenitor cells (EPC) and the vascular endothelial growth factor receptor (VEGFR) 2+ cells in the peripheral blood were increased in groups treated with AMD-3100. The expression of vascular endothelial growth factor (VEGF) was increased in response to expansion or AMD injection. The expression of stromal cell derived factor (SDF)-1 and VEGFR2 were increased only in unexpanded flap treated with AMD-3100. Treatment with AMD-3100 increased both the number and area of blood vessels. However, there were no statistically significant differences in the survival area or physiologic microcirculation in rats from the other groups. This endogenous neovascularization induced by AMD-3100 may be a result of the increase in both the area and number of vessels, as well as paracrine augmentation of the expression of VEGF and EPCs. However, the presence of a tissue expander under the flap could block the neovascularization between the flap and the recipient regardless of AMD-3100 treatment and expansion.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1412
[Cu] Class update date: 141206
[Lr] Last revision date:141206
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.3346/jkms.2014.29.S3.S237

  5 / 314116 MEDLINE  
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[PMID]: 25473269
[Au] Autor:Akhavanpoor M; Gleissner CA; Gorbatsch S; Doesch AO; Akhavanpoor H; Wangler S; Jahn F; Lasitschka F; Katus HA; Erbel C
[Ad] Address:Department of Cardiology, University of Heidelberg, Germany ; DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, Germany....
[Ti] Title:CCL19 and CCL21 modulate the inflammatory milieu in atherosclerotic lesions.
[So] Source:Drug Des Devel Ther;8:2359-71, 2014.
[Is] ISSN:1177-8881
[Cp] Country of publication:New Zealand
[La] Language:eng
[Ab] Abstract:Despite advances in the pharmacologic and interventional treatment of coronary artery disease, atherosclerosis remains the leading cause of death worldwide. Atherosclerosis is a chronic inflammatory disease, and elevated expression of CCL19 and CCL21 has been observed in ruptured lesions of coronary arteries of patients with myocardial infarction and carotid plaques of patients with ischemic symptoms, as well as in plasma of coronary artery disease patients. However, the exact role of CCL19 and CCL21 in atherosclerosis remains unknown. In order to identify CCL19 and CCL21 as a novel therapeutic target, we performed bone marrow transplantation as an immunomodulatory treatment concept. Bone marrow of plt/plt mice (lacking CCL19 and CCL21-Ser) was transplanted into atherogenic Ldlr (-/-) mice. The study demonstrated a significantly increased inflammatory cellular infiltration into the lesions of plt/plt/Ldlr (-/-) mice versus controls. Although the level of chemoattraction was increased, messenger ribonucleic acid and protein levels in thoracic aorta and serum of several proinflammatory cytokines (TNFα, IFNγ, IL-6, IL-12, and IL-17) were significantly reduced in plt/plt/Ldlr (-/-) versus control mice. Increased influx, accompanied by reduced activation of leukocytes in atherosclerotic lesion, was accompanied by increased plaque stability but unchanged lesion development. In conclusion, modulation of the chemokines CCL19 and CCL21 represents a potent immunoregulatory treatment approach, and thus represents a novel therapeutic target to stabilize atherosclerotic lesions.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1412
[Cu] Class update date: 141206
[Lr] Last revision date:141206
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.2147/DDDT.S72394

  6 / 314116 MEDLINE  
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[PMID]: 25464512
[Au] Autor:Xiao Z; Cao L; Liang Y; Huang J; Stern AR; Dallas M; Johnson M; Quarles LD
[Ad] Address:Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, 38165, United States of America....
[Ti] Title:Osteoblast-specific deletion of pkd2 leads to low-turnover osteopenia and reduced bone marrow adiposity.
[So] Source:PLoS One;9(12):e114198, 2014.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Polycystin-1 (Pkd1) interacts with polycystin-2 (Pkd2) to form an interdependent signaling complex. Selective deletion of Pkd1 in the osteoblast lineage reciprocally regulates osteoblastogenesis and adipogenesis. The role of Pkd2 in skeletal development has not been defined. To this end, we conditionally inactivated Pkd2 in mature osteoblasts by crossing Osteocalcin (Oc)-Cre;Pkd2+/null mice with floxed Pkd2 (Pkd2flox/flox) mice. Oc-Cre;Pkd2flox/null (Pkd2Oc-cKO) mice exhibited decreased bone mineral density, trabecular bone volume, cortical thickness, mineral apposition rate and impaired biomechanical properties of bone. Pkd2 deficiency resulted in diminished Runt-related transcription factor 2 (Runx2) expressions in bone and impaired osteoblastic differentiation ex vivo. Expression of osteoblast-related genes, including, Osteocalcin, Osteopontin, Bone sialoprotein (Bsp), Phosphate-regulating gene with homologies to endopeptidases on the X chromosome (Phex), Dentin matrix protein 1 (Dmp1), Sclerostin (Sost), and Fibroblast growth factor 23 (FGF23) were reduced proportionate to the reduction of Pkd2 gene dose in bone of Oc-Cre;Pkd2flox/+ and Oc-Cre;Pkd2flox/null mice. Loss of Pkd2 also resulted in diminished peroxisome proliferator-activated receptor γ (PPARγ) expression and reduced bone marrow fat in vivo and reduced adipogenesis in osteoblast culture ex vivo. Transcriptional co-activator with PDZ-binding motif (TAZ) and Yes-associated protein (YAP), reciprocally acting as co-activators and co-repressors of Runx2 and PPARγ, were decreased in bone of Oc-Cre;Pkd2flox/null mice. Thus, Pkd1 and Pkd2 have coordinate effects on osteoblast differentiation and opposite effects on adipogenesis, suggesting that Pkd1 and Pkd2 signaling pathways can have independent effects on mesenchymal lineage commitment in bone.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1412
[Cu] Class update date: 141206
[Lr] Last revision date:141206
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1371/journal.pone.0114198

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[PMID]: 25460570
[Au] Autor:Orozco JJ; Balkin ER; Gooley TA; Kenoyer A; Hamlin DK; Wilbur DS; Fisher DR; Hylarides MD; Shadman M; Green DJ; Gopal AK; Press OW; Pagel JM
[Ad] Address:Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America; Hematology Division, University of Washington, Seattle, WA, United States of America....
[Ti] Title:Anti-CD45 Radioimmunotherapy with 90Y but Not 177Lu Is Effective Treatment in a Syngeneic Murine Leukemia Model.
[So] Source:PLoS One;9(12):e113601, 2014.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Radioimmunotherapy (RIT) for treatment of hematologic malignancies has primarily employed monoclonal antibodies (Ab) labeled with 131I or 90Y which have limitations, and alternative radionuclides are needed to facilitate wider adoption of RIT. We therefore compared the relative therapeutic efficacy and toxicity of anti-CD45 RIT employing 90Y and 177Lu in a syngeneic, disseminated murine myeloid leukemia (B6SJLF1/J) model. Biodistribution studies showed that both 90Y- and 177Lu-anti-murine CD45 Ab conjugates (DOTA-30F11) targeted hematologic tissues, as at 24 hours 48.8±21.2 and 156±14.6% injected dose per gram of tissue (% ID/g) of 90Y-DOTA-30F11 and 54.2±9.5 and 199±11.7% ID/g of 177Lu-DOTA-30F11 accumulated in bone marrow (BM) and spleen, respectively. However, 90Y-DOTA-30F11 RIT demonstrated a dose-dependent survival benefit: 60% of mice treated with 300 µCi 90Y-DOTA-30F11 lived over 180 days after therapy, and mice treated with 100 µCi 90Y-DOTA-30F11 had a median survival 66 days. 90Y-anti-CD45 RIT was associated with transient, mild myelotoxicity without hepatic or renal toxicity. Conversely, 177Lu- anti-CD45 RIT yielded no long-term survivors. Thus, 90Y was more effective than 177Lu for anti-CD45 RIT of AML in this murine leukemia model.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1412
[Cu] Class update date: 141206
[Lr] Last revision date:141206
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1371/journal.pone.0113601

  8 / 314116 MEDLINE  
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[PMID]: 25460165
[Au] Autor:Snider AJ; Ali WH; Sticca JA; Coant N; Ghaleb AM; Kawamori T; Yang VW; Hannun YA; Obeid LM
[Ad] Address:Northport Veterans Affairs Medical Center, Northport, New York, United States of America; Department of Medicine, Stony Brook University, Stony Brook, New York, United States of America; Stony Brook Cancer Center, Stony Brook University, Stony Brook, New York, United States of America....
[Ti] Title:Distinct roles for hematopoietic and extra-hematopoietic sphingosine kinase-1 in inflammatory bowel disease.
[So] Source:PLoS One;9(12):e113998, 2014.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Sphingosine kinase 1 (SK1), one of two SK enzymes, is highly regulated and has been shown to act as a focal point for the action of many growth factors and cytokines. SK1 leads to generation of sphingosine-1-phosphate (S1P) and potentially the activation of S1P receptors to mediate biologic effects. Our previous studies implicated SK1/S1P in the regulation of inflammatory processes, specifically in inflammatory bowel disease (IBD). These studies were conducted using a total body knockout mouse for SK1 and were unable to determine the source of SK1/S1P (hematopoietic or extra-hematopoietic) involved in the inflammatory responses. Therefore, bone marrow transplants were performed with wild-type (WT) and SK1-/- mice and colitis induced with dextran sulfate sodium (DSS). Irrespective of the source of SK1/S1P, bone marrow or tissue, DSS induced colitis in all mice; however, mice lacking SK1 in both hematopoietic and extra-hematopoietic compartments exhibited decreased crypt damage. Systemic inflammation was assessed, and mice with WT bone marrow demonstrated significant neutrophilia in response to DSS. In the local inflammatory response, mice lacking SK1/S1P in either bone marrow or tissue exhibited decreased induction of cytokines and less activation of STAT3 (signal transducer and activator of transcription 3). Interestingly, we determined that extra-hematopoietic SK1 is necessary for the induction of cyclooxygenase 2 (COX2) in colon epithelium in response to DSS-induced colitis. Taken together our data suggest that hematopoietic-derived SK1/S1P regulates specific aspects of the systemic inflammatory response, while extra-hematopoietic SK1 in the colon epithelium is necessary for the autocrine induction of COX2 in DSS-induced colitis.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1412
[Cu] Class update date: 141206
[Lr] Last revision date:141206
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1371/journal.pone.0113998

  9 / 314116 MEDLINE  
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[PMID]: 25132274
[Au] Autor:Li C; Luo T; Zheng Z; Murphy AR; Wang X; Kaplan DL
[Ad] Address:National Engineering Laboratory for Modern Silk, Soochow University, Suzhou 215123, China; Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA....
[Ti] Title:Curcumin-functionalized silk materials for enhancing adipogenic differentiation of bone marrow-derived human mesenchymal stem cells.
[So] Source:Acta Biomater;11:222-32, 2015 Jan 1.
[Is] ISSN:1878-7568
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Curcumin, a natural phenolic compound derived from the plant Curcuma longa, was physically entrapped and stabilized in silk hydrogel films, and its influence on human bone marrow-derived mesenchymal stem cells (hBMSC) was assessed related to adipogenic differentiation. The presence of curcumin significantly reduced the silk gelation time and changed the porous morphology of gel matrix, but did not change the formation of the silk beta-sheet structure. Based on spectrofluorimetric analysis, curcumin most likely interacted with hydrophobic residues in silk, interacting with the beta-sheet domains formed in the hydrogels. The antioxidant activity of silk film-associated curcumin remained functional over at least one month in both the dry and hydrated state. Negligible curcumin was released from silk hydrogel films over 48h incubation in aqueous solution. For hBMSC cultured on silk films containing more than 0.25mgml(-1) curcumin, cell proliferation was inhibited, while adipogenesis was significantly promoted based on transcripts as well as Oil Red O staining. When hBMSC were cultured in media containing free curcumin, both proliferation and adipogenesis of hBMSC were inhibited when curcumin concentrations exceeded 5µM, which is more than 1000times higher than the level of curcumin released from the films in aqueous solution. Thus, silk film-associated curcumin exhibited different effects on hBMSC proliferation and differentiation compared with curcumin in solution.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1412
[Cu] Class update date: 141206
[Lr] Last revision date:141206
[Js] Journal subset:IM
[St] Status:In-Data-Review

  10 / 314116 MEDLINE  
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[PMID]: 25437431
[Au] Autor:Zhu J; Bi Z; Yang T; Wang W; Li Z; Huang W; Wang L; Zhang S; Zhou Y; Fan N; Bai Y; Song W; Wang C; Wang H; Bi Y
[Ad] Address:School of Public Health, Wuhan University, Wuhan, Hubei, P.R. China; Hubei Key Laboratory of Allergy and Immune-related Diseases, Wuhan, Hubei, P.R. China; Hubei Biomass-resource Chemistry and Environmental Biotechnology Key Laboratory, Wuhan University, Wuhan, Hubei, P.R. China....
[Ti] Title:Regulation of PKM2 and Nrf2-ARE Pathway during Benzoquinone Induced Oxidative Stress in Yolk Sac Hematopoietic Stem Cells.
[So] Source:PLoS One;9(12):e113733, 2014.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Benzene is an occupational toxicant and an environmental pollutant that is able to induce the production of reactive oxygen species (ROS), causing oxidative stress and damages of the macromolecules in target cells, such as the hematopoietic stem cells. We had previously found that embryonic yolk sac hematopoietic stem cells (YS-HSCs) are more sensitive to benzene toxicity than the adult bone marrow hematopoietic stem cells, and that nuclear factor-erythroid-2-related factor 2 (Nrf2) is the major regulator of cytoprotective responses to oxidative stress. In the present report, we investigated the effect of PKM2 and Nrf2-ARE pathway on the cellular antioxidant response to oxidative stress induced by benzene metabolite benzoquinone (BQ) in YS-HSC isolated from embryonic yolk sac and enriched by magnetic-activated cell sorting (MACS). Treatment of the YS-HSC with various concentrations of BQ for 6 hours induces ROS generation in a dose-dependent manner. Additional tests showed that BQ is also capable of inducing expression of NADPH oxidase1 (NOX1), and several other antioxidant enzymes or drug-metabolizing enzymes, including heme oxygenase 1 (HMOX1), superoxide dismutase (SOD), catalase and NAD(P)H dehydrogenase quinone 1 (NQO1). Concomitantly, only the expression of PKM2 protein was decreased by the treatment of BQ but not the PKM2 mRNA, which suggested that BQ may induce PKM2 degradation. Pretreatment of the cells with antioxidant N-acetylcysteine (NAC) decreased ROS generation and prevented BQ-induced PKM2 degradation, suggesting involvement of ROS in the PKM2 protein degradation in cellular response to BQ. These findings suggest that BQ is a potent inducer of ROS generation and the subsequent antioxidant responses of the YS-HSC. The accumulated ROS may attenuate the expression of PKM2, a key regulator of the pyruvate metabolism and glycolysis.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1412
[Cu] Class update date: 141206
[Lr] Last revision date:141206
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1371/journal.pone.0113733


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