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| 1 | TLR4 signaling and the inhibition of liver hepcidin expression by alcohol显示文摘AIM:To understand the role of toll-like receptor 4(TLR4)signaling in the regulation of iron-regulatory hormone,hepcidin by chronic alcohol consumption.METHODS:For chronic alcohol intake studies,TLR4mutant mice on C3H/HeJ background and wildtype counterpart on C3H/HeOuJ background were pair-fed with regular(control)and ethanol-containing Lieber De Carli liquids diets.Gene expression was determined by real-time quantitative PCR.Protein-protein interactions and protein expression were determined by co-immunoprecipitation and western blotting.The occupancy of hepcidin gene promoter was determined by chromatin immunoprecipitation assays.RESULTS:Chronic alcohol intake suppressed hepcidin mRNA expression in the livers of wildtype,but not TLR4 mutant,mice.The phosphorylation and nuclear translocation of nuclear factor(NF)-κB p65 subunit protein was observed in alcohol-fed wildtype,but not in alcohol-fed TLR4 mutant,mice.Similarly,alcohol induced the binding of NF-κB p50 subunit protein to hepcidin gene promoter in wildtype,but not in TLR4mutant,mice.In contrast,the phosphorylation of Stat3in the liver was stronger in alcohol-treated TLR4 mutant mice compared to alcohol-treated wildtype mice.The occupancy of hepcidin gene promoter by Stat3was observed in alcohol-fed mutant,but not in wildtype,mice.An interaction between NF-κB p65 subunit protein and small heterodimer partner protein(SHP)was observed in the livers of both wildtype and TLR4mutant mice fed with the control diet,as shown by coimmunoprecipitation studies.Alcohol intake elevated cytosolic SHP expression but attenuated its interaction with NF-κB in the liver,which was more prominent in the livers of wildtype compared to TLR4 mutant mice.CONCLUSION:Activation of TLR4 signaling and NF-кB are involved in the suppression of hepcidin gene transcription by alcohol in the presence of inflammation in the liver. | Emily Zmijewski Sizhao Lu Duygu Dee Harrison-Findik | 2014 | World Journal of Gastroenterology2014，20，34： | 6 |
| 2 | Effect of alcohol exposure on hepatic superoxide generation and hepcidin expression显示文摘AIM: To understand the role of mitochondrial-produced superoxide(O 2 ?) in the regulation of iron-regulatory hormone, hepcidin by alcohol in the liver. METHODS: For alcohol experiments, manganese superoxide dismutase knockout mice heterozygous for Sod2 gene expression(Sod2 +/) and age-matched littermate control mice(LMC), expressing Sod2 gene on both alleles, were exposed to either 10%(w/v) ethanol in the drinking water or plain water(control) for 7 d. Total cellular O 2 ? levels in hepatocytes isolated from the livers of mice were measured by electron paramagnetic resonance spectroscopy. The mitochondrial-targeted, O 2 ?-sensitive fluorogenic probe, MitoSOX Red and flow cytometry were utilized to measure O 2 ? in mitochondria. Gene and protein expression were determined by Taqman Real-time quantitative PCR and Western blotting, respectively. RESULTS: Sod2 +/- mice expressed 40% less MnSOD protein(SOD2) in hepatocytes compared to LMC mice. The deletion of Sod2 allele did not alter the basal expression level of hepcidin in the liver. 10% ethanol exposure for 1 wk inhibited hepatic hepcidin mRNA expression three-fold both in Sod2 +/ and LMC mice. O 2 ? levels in hepatocytes of untreated Sod2 +/ mice were three-fold higher than in untreated LMC mice, as observed by electron paramagnetic resonance spectroscopy. O 2 ? levels in mitochondria of Sod2 +/ mice were four-fold higher than in mitochondria of untreated LMC mice, as measured by MitoSOX Red fluorescence and flow cytometry. Alcohol induced a two-fold higher increase in O 2 ? levels in hepatocytes of LMC mice than in Sod2 +/ mice compared to respective untreated counterparts. In contrast, 1 wk alcohol exposure did not alter mitochondrial O 2 ? levels in both Sod2 +/- and control mice. CONCLUSION: Mitochondrial O2 ? is not involved in the inhibition of liver hepcidin transcription and thereby regulation of iron metabolism by alcohol. These findings also suggest that short-term alcohol consumption significantly elevates O 2 ? levels in hepatocytes, which appears not to originate from mitochondria. | Duygu Dee Harrison-Findik Sizhao Lu Emily M Zmijewski Jocelyn Jones Matthew C Zimmerman | 2013 | World Journal of Biological Chemistry2013，4，4： | 2 |
| 3 | Some Economic Determinants of Accounting Policy Choice显示文摘 | HAGERMAN R L ZMIJEWSKI M E | 1979 | Journal of Account- ing and Economics1979，1，2： | 1 |
| 4 | Methodological Issues Related to the Estimation of Financial Distress Prediction Models显示文摘 | Zmijewski M.E | | 0，，： | 1 |
| 5 | Methodological issues related to the estimation of financial distress frediction model显示文摘 | Zmijewski M E | 1984 | Journal of Accounting Research1984，，： | 1 |
| 6 | An income strategy approach to the positive theory of accounting standard setting and choice显示文摘 | ZMIJEWSKI M HAGERMAN R | 1981 | Journal of Accounting and Economics1981，，3： | 1 |
| 7 | Direct, activating interaction between glycogen synthase kinase 3beta and p53 after DNA damage显示文摘 | Watcharasit P Bijur GN Zmijewski JW | 2002 | Proc Natl Acad Sci USA2002，99，12： | 1 |
| 8 | Methodological issues related to the estimation of financial distress prediction models显示文摘 | Zmijewski M E | 1984 | Journal of Accounting Research (Supplement)1984，，： | 1 |
| 9 | Cross-Sectional Variation in the Stock Market Response to Accounting Earnings Announcements显示文摘 | Easton P D Zmijewski M E | 1991 | Journal of Accounting and Economics1991，7，： | 1 |
| 10 | The relative informativeness of accounting disclosures in different countries 显示文摘 | Alford A J Jones R Leftwich M Zmijewski | 1993 | Journal of Accounting Research1993，31，： | 1 |
| 11 | Participation of Mammalian Target of Rapamycin Complex 1 in Toll-Like Receptor 2-and 4-Induced Neutrophil Activation and Acute Lung Injury显示文摘 | Lorne E Zhao X Zmijewski J W | 2009 | American journal of respiratory cell and molecular biology2009，41，2： | 1 |
| 12 | Participation of mamma- lian target of rapamycin complex 1 in Toll like receptor 2- and 4-induced neutrophil activation and acute lung injury显示文摘 | Lorne E Zhao X Zmijewski JW | 2009 | Am J Respir Cell Mol Biol2009，41，2： | 1 |
| 13 | Methodological Issues Related to the Estimation of Financial Distress Prediction Models显示文摘 | Zmijewski M | 1984 | Journal of Accounting Research1984，，： | 1 |
| 14 | HMGB1 develops enhanced proinflammatory activity by binding to cytokines 显示文摘 | Sha Y Zmijewski J Xu Z | 2008 | J Immunol2008，180，4： | 1 |
| 15 | HMGB1 develops enhanced proinflammatory activity by binding to cytokines显示文摘 | Sha Y Zmijewski J Xu Z | | 0，，04： | 1 |
| 16 | Some economic determinants of accounting policy choice显示文摘 | HAGERMAN R ZMIJEWSKI M | 1979 | Journal of Accounting and Economics1979，1，2： | 1 |
| 17 | Security Analyst Superiority Relative to Univariate Time-Series Models in Forecasting Quarterly Earnings 显示文摘 | Brown L D R L Hagerman P A Griffin M E Zmijewski | 1987 | Journal of Account- ing and Economics1987，，9： | 1 |
| 18 | develops enhanced proin- flammatory activity by binding to cytokines 显示文摘 | L Xn HMGB1 Sha Y Zmijewski J Z | 2008 | J hnmunol2008，180，： | 1 |
| 19 | Methodological issues related to tile estimation of financial distress prediction models 显示文摘 | Zmijewski | 1984 | Journal of Accounting Research (Supplement)1984，22，： | 1 |
| 20 | Melatonin as a major skin protectant: from free radical scavenging to DNA damage repair 显示文摘 | Fischer TW Slominski A Zmijewski MA | 2008 | Exp Dermatol2008，17，9： | 1 |
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