金月芽期刊網

和“oxygenase-1”相關的論文

  • 促進小鼠骨髓間充質干細胞增殖和成骨分化的血管內皮生長因子 相關:干細胞 骨髓干細胞 血管內皮生長因子
  • 背景:血管內皮生長因子是骨髓間充質干細胞所處骨髓微環境中的重要調控因子,其可促進骨髓間充質干細胞的血管內皮方向分化,但尚無其對骨髓間充質干細胞增殖和成骨分化調控作用的報道。目的:探討血管內皮生長因子對骨髓間充質干細胞增殖和成骨分化的調控作用及其機制。方法:分離、培養小鼠骨髓間充質干細胞,CCK8方法檢測不同質量濃度血管內皮生長因子重組蛋白對骨髓間充質干細胞增殖的影響,選定適宜血管內皮生長因子重組蛋白質量濃度并檢測其對骨髓間充質干細胞成骨分化的影響,分子生物學方法檢測血管內皮生長因子干預下骨髓間充質干細胞中Osterix,Runx2,堿性磷酸?、骨鈣素和血紅素氧化?1的表達。結果與結論:?血管內皮生長因子可以促進骨髓間充質干細胞增殖,且具有濃度依賴性,100μg/L血管內皮生長因子重組蛋白的促增殖作用最顯著。?成骨誘導劑存在條件下,血管內皮生長因子促進骨髓間充質干細胞成骨標志基因Osterix、Runx2、堿性磷酸?和骨鈣素的表達;血管內皮生長因子干預組骨髓間充質干細胞成骨分化的鈣結節數量較對照組增加。?血管內皮生長因子可誘導骨髓間充質干細胞中血紅素氧化?1 mRNA和蛋白水平的高表達。以上結果表明血管內皮生長因子促進骨髓間充質干細胞增殖和向成骨細胞分化的調控機制可能與骨髓間充質干細胞內血紅素氧化?1表達增加有關。
  • Inhibiting heme oxygenase-1 attenuates rat liver fibrosis by removing iron accumulation 相關:Heme oxygenase-1 HEPCIDIN
  • AIM:To investigate the effects of the heme oxygenase(HO)-1/carbon monoxide system on iron deposition and portal pressure in rats with hepatic fibrosis induced by bile duct ligation(BDL).METHODS:Male Sprague-Dawley rats were divided randomly into a Sham group,BDL group,Fe group,deferoxamine(DFX) group,zinc protoporphyrin(ZnPP) group and cobalt protoporphyrin(CoPP) group.The levels of HO-1 were detected using different methods.The serum carboxyhemoglobin(COHb),iron,and portal vein pressure(PVP) were also quantified.The plasma and mRNA levels of hepcidin were measured.Hepatic fibrosis and its main pathway were assessed using Van Gieson’s stain,hydroxyproline,transforming growth factor-β1(TGF-β1),nuclear factor-E2-related factor 2(Nrf2),matrix metalloproteinase-2(MMP-2) and tissue inhibitor of metalloproteinase-1(TIMP-1).RESULTS:Serum COHb and protein and mRNA expression levels of HO-1 and Nrf2 were increased in the BDL group compared with the Sham group and were much higher in the CoPP group.The ZnPP group showed lower expression of HO-1 and Nrf2 and lower COHb.The levels of iron and PVP were enhanced in the BDL group but were lower in the ZnPP and DFX groups and were higher in the CoPP and Fe groups.Hepcidin levels were higher,whereas superoxide dismutase levels were increased and malonaldehyde levels were decreased in the ZnPP and DFX groups.The ZnPP group also showed inhibited TGF-β1 expression and regulated TIMP-1/MMP-2 expression,as well as obviously attenuated liver fibrosis.CONCLUSION:Reducing hepatic iron deposition and CO levels by inhibiting HO-1 activity though the Nrf2/Keap pathway could be helpful in improving hepatic fibrosis and regulating PVP.
  • Zinc protoporphyrin IX enhances chemotherapeutic response of hepatoma cells to cisplatin 相關:ZINC protoporphyrin iX
  • AIM:To investigate the effect of zinc protoporphyrin IX on the response of hepatoma cells to cisplatin and the possible mechanism involved.METHODS:Cytotoxicity was determined using the3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Apoptosis was determined by a flow cytometric assay.Western blotting was used to measure protein expression.Heme oxygenase(HO)-1 activity was measured by determining the level of bilirubin generated in isolated microsomes.Reactive oxygen species(ROS)production was monitored by flow cytometry.Caspase-3 activity was measured with a colorimetric assay kit.Mice were inoculated with 1×107 tumor cells subcutaneously into the right flanks.All mice were sacrificed 6 wk after the first treatment and tumors were weighed and measured.RESULTS:Overexpression of HO-1 in HepG2 cell line was associated with increased chemoresistance to cisdiaminedichloroplatinum(cisplatin;CDDP)compared to other cell lines in vitro.Inhibition of HO-1 expression or activity by zinc protoporphyrin IX(ZnPP IX)markedly augmented CDDP-mediated cytotoxicity towards all liver cancer cell lines in vitro and in vivo.In contrast,induction of HO-1 with hemin increased resistance of tumor cells to CDDP-mediated cytotoxicity in vitro and in vivo.Furthermore,cells treated with ZnPP IX plus CDDP exhibited marked production of intracellular ROS and caspase-3 activity,which paralleled the incidence of cell apoptosis,whereas hemin decreased cellular ROS and caspase-3 activity induced by CDDP.CONCLUSION:ZnPP IX increases cellular sensitivity and susceptibility of liver cancer cell lines to CDDP and this may represent a mechanism of increasing ROS.
  • Heme oxygenase-1 protects rat liver against warm ischemia/reperfusion injury via TLR2/TLR4-triggered signaling pathways 相關:Heme oxygenase-1 Ischemia
  • AIM:To investigate the efficacy and molecularmechanisms of induced heme oxygenase(HO)-1 in protecting liver from warm ischemia/reperfusion(I/R)injury.METHODS:Partial warm ischemia was produced in the left and middle hepatic lobes of SD rats for 75min,followed by 6 h of reperfusion.Rats were treated with saline,cobalt protoporphyrin(Co PP)or zinc protoporphyrin(Zn PP)at 24 h prior to the ischemia insult.Blood and samples of ischemic lobes subjected to ischemia were collected at 6 h after reperfusion.Serum transaminases level,plasma lactate dehydrogenase and myeloperoxidase activity in liver were measured.Liver histological injury and inflammatory cell infiltration were evaluated by tissue section and liver immunohistochemical analysis.We used quantitative reverse transcription polymerase chain reaction to analyze liver expression of inflammatory cytokines and chemokines.The cell lysates were subjected to immunoprecipitation with anti-Toll-IL-1R-containing adaptor inducing interferon-β(TRIF)and anti-myeloid differentiation factor 88(My D88),and then the immunoprecipitates were analyzed by SDS-PAGE and immunoblotted with the indicated antibodies.RESULTS:HO-1 protected livers from I/R injury,as evidenced by diminished liver enzymes and wellpreserved tissue architecture.In comparison with Zn PP livers 6 h after surgery,Co PP treatment livers showed a significant increase inflammatory cell infiltration of lymphocytes,plasma cells,neutrophils and macrophages.The Toll-like receptor(TLR)-4 and TANK binding kinase1 protein levels of rats treated with Co PP significantly reduced in TRIF-immunoprecipitated complex,as compared with Zn PP treatment.In addition,pretreatment with Co PP reduced the expression levels of TLR2,TLR4,IL-1R-associated kinase(IRAK)-1 and tumor necrosis factor receptor-associated factor 6 in My D88-immunoprecipitated complex.The inflammatory cytokines and chemokines m RNA expression rapidly decreased inCo PP-pretreated liver,compared with the Zn PP-treat...
  • 1,2,3,4,6-penta-O-galloyl-β-D-glucose Protects PC12 Cells from MPP~+-mediated Cell Death by Inducing Heme Oxygenase-1 in an ERK-and Akt-dependent Manner 相關:1,2,3,4,6-penta-O-galloyl-β-D-glucose (β-PGG) heme
  • This study examined the ability of 1,2,3,4,6-penta-O-galloyl-β-D-glucose (β-PGG) to induce the expression of heme oxygenase-1 (HO-1) in the PC12 cells and its regulation in the PC12 cells.One week before treatment with the drug,nerve growth factor (NGF) was added to the cultures at a final concentration of 50 ng/mL to induce neuronal differentiation.After drug treatment,HO-1 gene transcription was analyzed by reverse transcription polymerase chain reaction (RT-PCR).Expression of HO-1 and NF-E2-related factor2 (Nrf2) and activation of extracellular signal-regulated kinase (ERK) and Akt were detected by Western blotting.The viability of the PC12 cells treated with different medicines was examined by MTT assay.The oxidative stress in the PC12 cells was evaluated qualitatively and quantitatively by DCFH-DA.The results showed that β-PGG up-regulated HO-1 expression and this increased expression provided neuroprotection against MPP+-induced oxidative injury.Moreover,β-PGG induced Nrf2 nuclear translocation,which was found to be upstream of β-PGG-induced HO-1 expression,and the activation of ERK and Akt,a pathway that is involved in β-PGG-induced Nrf2 nuclear translocation,HO-1 expression and neuroprotection.In conclusion,β-PGG up-regulates HO-1 expression by stimulating Nrf2 nuclear translocation in an ERK-and Akt-dependent manner,and HO-1 expression by β-PGG may provide the PC12 cells with an acquired antioxidant defense capacity to survive the oxidative stress.
  • 慢病毒介導的血紅素加氧?-1對脂肪干細胞在低氧無血清條件下的保護作用 相關:慢病毒屬 血紅素加氧?-1 細胞凋亡
  • 目的:探討慢病毒介導的血紅素加氧?-1(HO-1)對脂肪干細胞(ADSCs)在低氧無血清的條件下的保護作用。方法分離培養SD大鼠ADSCs,取第三代ADSCs分為五組:對照組;單純低氧無血清組;空載體病毒組;HO-1組;HO-1+ZnPP組。采用DAPI染色檢測各組細胞凋亡率;Western blot法檢測各組HO-1、Cleaved-Caspase-3的表達量。結果攜帶HO-1基因的慢病毒轉染ADSCs(HO-1組)可明顯增加ADSCs中HO-1的表達;ADSCs在缺氧狀態下發生大量凋亡,其凋亡率為(27.29±1.18)%,轉空載體的細胞凋亡率達(27.47±1.35)%,而轉HO-1基因的ADSCs的凋亡率僅為(12.00±1.18)%,HO-1+ZnPP組:凋亡率(25.52±2.98)%。與對照組相比,低氧無血清組與空載體病毒組ADSCs的Cleaved-Caspase-3的表達有顯著升高(P<0.05);HO-1組Cleaved-Caspase-3的表達與低氧無血清組與空載體病毒組相比有明顯下降( P<0.05);而HO-1+ZnPP組Cleaved-Caspase-3的表達又明顯高于HO-1組(P<0.05)。結論提高ADSCs中HO-1蛋白的表達可以通過降低凋亡效應因子Caspase-3的活性顯著降低ADSCs在低氧無血清條件下的凋亡率。
  • 蘭索拉唑對幽門螺桿菌誘導人胃上皮細胞產生IL-1β和IL-8的影響 相關:蘭索拉唑 幽門螺桿菌 胃上皮細胞
  • 目的:探討蘭索拉唑對幽門螺桿菌(helicobacter pylori,Hp)感染的胃上皮細胞的體外抗炎效應。方法體外培養胃上皮細胞系AGS,加入蘭索拉唑和培養的Hp感染不同時間。ELISA檢測IL-1β和IL-8的產生,Western blot檢測NF-κB p 65亞基的核轉位以及紅素氧合?1(Heme oxygenase-1, HO-1)蛋白表達水平。結果蘭索拉唑孵育8 h后,能顯著抑制Hp誘導的IL-1β和IL-8。同時,蘭索拉唑能抑制NF-κB p 65亞基的核轉位,并能上調HO-1蛋白的表達。結論蘭索拉唑可能通過抑制NF-κB的激活,上調HO-1的表達而發揮對胃上皮細胞的抗炎作用。
  • Toll樣受體-2和血紅素加氧?-1在復發性鼻息肉中的表達及意義 相關:Toll樣受體-2 血紅素加氧?-1 復發性鼻息肉
  • 目的:研究復發性鼻息肉組織中TLR-2、HO-1的表達和意義,并探討2者表達與鼻息肉復發的關系.方法采用免疫蛋白印記技術,檢測復發性鼻息肉組20例組織、鼻息肉組20例組織及正常對照組20例鉤突粘膜組織中TLR-2、HO-1蛋白表達情況,并比較分析2者之間的關系.結果復發性鼻息肉組織中TLR-2、HO-1的表達量與鼻息肉組織相比差異有統計學意義(P〈0.05);鼻息肉組織中TLR-2、HO-1的表達量與正常鼻黏膜組織相比差異有統計學意義(P〈0.05);TLR-2和HO-1在各組的表達量存在明顯的相關性(P〈0.05).結論 TLR-2、HO-1在鼻息肉復發機制中發揮著重要作用,2者可能作為鼻息肉患者術后隨診和復發趨勢判斷的客觀指標.
  • 骨髓增生異常綜合征患者血紅素加氧?表達水平及其臨床意義 相關:血紅素加氧?-1 骨髓增生異常綜合征 C-JUN氨基末端激?
  • 目的:觀察初診低危骨髓增生異常綜合征(MDS)患者血紅素加氧?-1(HO-1)表達水平的變化及其基礎水平與患者預后的關系,探討HO-1在該病中可能的作用機制和臨床應用前景。方法收集60例初診低危 MDS 患者以及20例缺鐵性貧血(IDA)患者的骨髓單個核細胞(BMMNCs),予不同濃度(0、5、10、20μM)的HO-1誘導劑Hemin體外孵育,用蛋白免疫印跡法檢測HO-1蛋白表達水平和MAPK信號通路中c-Jun氨基末端激?(JNK)磷酸化表達水平的變化,并隨訪分析HO-1的基礎表達水平與患者無進展生存期(PFS)的關系。結果?低危 MDS 患者BMMNCs中HO-1蛋白基礎表達水平與IDA患者比較差異無統計學意義(P>0.05);隨著Hemin干預濃度的增加,HO-1蛋白表達量逐漸升高,JNK信號分子磷酸化表達水平亦逐漸升高,呈濃度依賴性(均為P<0.05);? HO-1高表達的患者PFS長于低表達患者組(中位數41.6個月 vs.32.0個月,P=0.047)。COX回歸分析顯示HO-1表達水平是判斷低危MDS患者預后的獨立因素(P=0.006)。結論在低危MDS患者中,HO-1高表達者預后較好,HO-1可能通過JNK信號分子途徑影響MDS的疾病過程。上調HO-1有可能成為改善疾病預后的新的治療靶點。
  • PE P-1-血紅素加氧?-1融合蛋白預處理對L02肝細胞缺氧復氧損傷的影響 相關:PEP-1? 血紅素加氧?-1 肝細胞
  • 目的:評價細胞穿透?PEP-1介導血紅素加氧?-1(HO-1)預處理對L02肝細胞缺氧復氧損傷的影響。方法利用基因工程手段表達和純化融合蛋白PEP-1-HO-1(PEP-1-heme oxy-genase-1,PEP-1-HO-1)。使用人肝細胞株(HL-7702)建立培養人肝細胞缺氧復氧模型。按實驗需要以10%新生牛血清的DMEM液靜置培養L02肝細胞,將細胞進行隨機分為7組:A組,正常對照組(常規培養);B組,缺氧復氧組(缺氧復氧組細胞缺氧18 h,復氧6 h);C組,PEP-1-HO-1預處理組,按PEP-1-HO-1濃度分為5亞組(C1,0.125μmol/L;C2,0.25μmol/L ;C3,0.5μmol/L;C4,1.0μmol/L;C5,2.0μmol/L,缺氧前以PEP-1-HO-1融合蛋白預處理2 h,缺氧18 h,復氧6 h)。復氧結束后,收集各組細胞及培養液上清,檢測MDA、LDH、AST、ALT含量及SOD活性。結果缺氧復氧組較正常對照組相比,MDA、LDH、AST及ALT水平明顯升高(P<0.05),而 SOD 水平下降(P<0.05);PEP-1-HO-1預處理組與缺氧復氧組相比,預處理組能明顯降低MDA、LDH、AST及ALT水平(P<0.05),使得SOD水平上升(P<0.05),且在一定濃度下與劑量呈正相關。結論 PEP-1-HO-1融合蛋白預處理可減輕細胞缺氧復氧損傷。