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| 1 | High levels of homocysteine downregulate apolipoprotein E expression via nuclear factor kappa B显示文摘AIM: To investigate the effect of high homocysteine(Hcy) levels on apolipoprotein E(apoE) expression and the signaling pathways involved in this gene regulation.METHODS: Reverse transcriptase polymerase chain reaction(RT-PCR) and Western blot were used to assess apo E expression in cells treated with various concentrations(50-500 μmol/L) of Hcy. Calcium phosphatetransient transfections were performed in HEK-293 and RAW 264.7 cells to evaluate the effect of Hcy on apoE regulatory elements [promoter and distal multienhancer 2(ME2)]. To this aim, plasmids containing the proximal apoE promoter [(-500/+73)apoE construct] alone or in the presence of ME2 [ME2/(-500/+73)apoE construct] to drive the expression of the reporter luciferase gene were used. Co-transfection experiments were carried out to investigate the downstream effectors of Hcymediated regulation of apoE promoter by using specific inhibitors or a dominant negative form of IKβ. In other co-transfections, the luciferase reporter was under the control of synthetic promoters containing multiple specific binding sites for nuclear factor kappa B(NF-κB), activator protein-1(AP-1) or nuclear factor of activated T cells(NFAT). Chromatin immunoprecipitation(ChI P)assay was accomplished to detect the binding of NF-κB p65 subunit to the apoE promoter in HEK-293 treated with 500 μmol/L Hcy. As control, cells were incubated with similar concentration of cysteine. NF-κB p65 proteins bound to DNA were immunoprecipitated with anti-p65 antibodies and DNA was identified by PCR using primers amplifying the region-100/+4 of the apoE gene. RESULTS: RT-PCR revealed that high levels of Hcy(250-750 μmol/L) induced a 2-3 fold decrease in apoE m RNA levels in HEK-293 cells, while apo E gene expression was not significantly affected by treatment with lower concentrations of Hcy(100 μmol/L). Immunoblotting data provided additional evidence for the negative role of Hcy in apoE expression. Hcy decreased apoE promoter activity, in the presence or absence of ME2, in a dose dependent manner, in both RAW 264.7 and HEK-293 cells, as revealed by transient transfection experiments. The downstream effectors of the signaling pathways of Hcy were also investigated. The inhibitory effect of Hcy on the apo E promoter activity was counteracted by MAPK/ERK kinase 1/2(MEK1/2) inhibitor U0126, suggesting that MEK1/2 is involved in the downregulation of apoE promoter activity by Hcy. Our data demonstrated that Hcy-induced inhibition of apoE took place through activation of NF-κB. Moreover, we demonstrated that Hcy activated a synthetic promoter containing three NF-κB binding sites, but did not affect promoters containing AP-1 or NFAT binding sites. ChI P experiments revealed that NF-κB p65 subunit is recruited to the apoE promoter following Hcy treatment of cells.CONCLUSION: Hcy-induced stress negatively modulates apoE expression via MEK1/2 and NF-κB activation. The decreased apo E expression in peripheral tissues may aggravate atherosclerosis, neurodegenerative diseases and renal dysfunctions. | Violeta G Trusca Adina D Mihai Elena V Fuior Ioana M Fenyo Anca V Gafencu | 2016 | World Journal of Biological Chemistry2016，7，1： | 6 |
| 2 | Review of fuel processing catalysts for hydrogen production in PEM fuel cell systems 显示文摘 | ANCA F G | 2002 | Current Opinion in Solid State and Materials Science2002，6，5： | 1 |
| 3 | A peroxidase gene promoter induced by phytopathogens and Methyl Jasmonate in transgenic plant显示文摘 | Mark D C Anne L R Anca G R | 1997 | Molecular Plant-Microbe Interactions1997，10，： | 1 |
| 4 | CD105/Ki67 double immunnos- raining expression in liver metastasis from colon carcinoma显示文摘 | Raluca A Anca M Pusa G | 2011 | Rom J Morphol Embryo12011，52，2： | 1 |
| 5 | Investigation of Aeromonas hydrophila presence in trouts and hatchery environment by targeting ah and ahp virulence genes 显示文摘 | Laurentiu T Anca M G Aneta L T | 2013 | Current Opinion in Biotechnology2013，24，1： | 1 |
| 6 | A peroxidase gene promoter induced by phytopathogens and Methyl Jasmonate in transgenic plant 显示文摘 | Mark Curtis D Anne Rae L Anca Rusu G | 1997 | Molecular Plant Microbe interactions1997，，10： | 1 |
| 7 | DNA adsorption on a poly-L-lysine-immobilized poly ( 2-hydroxyethyl methacrylate ) membrane显示文摘 | Senel S Bayramoglu G Anca M Y | 2003 | Polymer International2003，52，7： | 1 |
| 8 | Effects of a red clover extract(MF11RCE)on endometrium and sex hormones in postmenopausal women显示文摘 | Anca G Franz R | 2006 | Maturitas2006，55，： | 1 |
| 9 | Effects of a red clover extract(MFllRCE) on endometrium and sex hormones in postmenopansal women 显示文摘 | Martin I Anca G Franz R | 2006 | Maturitas2006，55，1： | 1 |
| 10 | Enzymatic removal of phenol and p-chlo- rophenol in enzyme reactor: Horseradish peroxidase immobilized on magnetic beads 显示文摘 | Bayramoglu G Anca MY | 2008 | Journal of Hazardous Materials2008，156，13： | 1 |
| 11 | Shanahan perceptual organization for inferring object boundaries in an image 显示文摘 | Anca L Raleseu James G | 1999 | Pattern recognition1999，32，： | 1 |
| 12 | SunCHem:an integrated process for the hydrothermal production of methane from microalgae and CO 2 mitigation显示文摘 | Anca G Haiduc Martin Brandenberger Sebastien Suquet | 2009 | Journal of Applied Phycology2009，21，： | 1 |
| 13 | Enzymatic Removal of Phenol and p-Chlorophenol in Enzyme Reactor:Horseradish Peroxidase Immobilized on Magnetic Beads显示文摘 | Bayramo G Anca M Y | 2008 | J Hazard Mater2008，156，13： | 1 |
| 14 | Effects of a red clover extract (MF11RCE) on endometrium and sex hormones in postmenopausal women 显示文摘 | MARTIN I ANCA G FRANZ R | 2006 | Maturitas2006，55，： | 1 |
| 15 | Affinity dyeligand poly(hydroxyethyl methacrylate)/chitosan composite membrane for adsorption lysozyme and kinetic properties显示文摘 | Bayramoglu G Yglmaz M Anca MY | | 0，，01： | 1 |
| 16 | Ethylenediamine grafted poly( glycidylmethacrylate-co-methylmethacry- late) adsorbent for removal of chromate anions 显示文摘 | B ayramoglu G Anca M Y | 2005 | Separation and Purification Technology2005，45，3： | 1 |
| 17 | CD105/Ki67 double immunnostaining expression in liver metastasis from colon carcinoma显示文摘 | Raluca A Anca M Pusa G | 2011 | Rom J Morphol Embryol2011，52，2： | 1 |
| 18 | Transient immune hepatitis as post-coronavirus disease complication:A case report显示文摘BACKGROUND We report a case of post-coronavirus disease(COVID)immune hepatitis occurring in a young male with no pre-existing comorbidities.CASE SUMMARY A previously healthy 21-year-old male patient was admitted to our hospital with mild COVID-19.During the course of in-hospital isolation and monitoring,he developed an alanine aminotransferase(ALT)and aspartate aminotransferase(AST)increase,with the enzymes peaking at day 24(ALT 15 times the upper normal limit),with preserved liver function.The liver enzyme increase occurred 20 d after the complete clinical remission of COVID-19,and ALT dynamics paralleled the increase in total antibodies against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).The case was interpreted as post-COVID immune hepatitis,with extensive laboratory investigations excluding other potential causes.The hepatocytolysis remitted 20 d after the peak ALT,without further intervention,with complete recovery,but the total anti-SARS-CoV-2 antibodies continued to increase the next 5 mo following the acute infection.CONCLUSION Close attention should also be paid to young patients with mild forms of disease,and a high index of suspicion should be maintained for post-COVID complications. | Anca Cristina Drăgănescu Oana Săndulescu Anuța Bilașco Camelia Kouris Anca Streinu-Cercel Monica Luminos Adrian Streinu-Cercel | 2021 | World Journal of Clinical Cases2021，9，16： | 0 |
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