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研究生:陳雅鈴
研究生(外文):Ya-Ling Chen
論文名稱:利用腺病毒攜帶人類第一型血基質氧化酵素於膽管結紮動物之研究
論文名稱(外文):Adenovirus-mediated Human Heme Oxygenase-1 Gene Transfer in Bile-duct Ligated Animals
指導教授:謝淑珠謝淑珠引用關係
指導教授(外文):Shu-Chu Shiesh
學位類別:碩士
校院名稱:國立成功大學
系所名稱:醫事技術學系
學門:醫藥衛生學門
學類:醫學技術及檢驗學類
論文種類:學術論文
論文出版年:2005
畢業學年度:93
語文別:中文
論文頁數:98
中文關鍵詞:腺病毒血基質氧化酵素膽汁鬱滯
外文關鍵詞:AdenovirusHeme Oxygenase-1Cholestasis
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  膽汁鬱滯是指膽汁的形成或流動發生障礙的病態情形,會發生在很多肝病患者。有許多的證據指出氧化壓力在膽汁鬱滯致成之肝傷害中扮演重要的角色。第一型血基質氧化酵素(heme oxygenase-1, HO-1)是可以被誘發的壓力性蛋白質 ,同時也是細胞分解代謝血基質的速率決定步驟酵素。研究指出HO-1參與抗發炎、抗細胞凋亡及提供細胞保護防禦機制以對抗氧化壓力所的造成傷害。HO-1已被報導在膽管結紮後在肝臟的表現會上升。然而,在膽汁鬱滯期間是否可利用外源性HO-1提供肝細胞保護的功能免於損害則並不清楚。因此,本研究利用構築重組腺病毒攜帶人類HO-1 (Ad-hHO-1),在ICR小鼠膽管結紮前一天給予腹腔注射氯化鈷(血基質氧化酵素化學刺激劑),或前三天給予(Ad-hHO-1),或重組腺病毒(Ad-LacZ),分別在膽管結紮後一天、三天、七天、十四天犧牲小鼠,測定血清中AST、ALT、膽紅素的濃度及病理組織切片染色,評估膽汁鬱滯肝傷害的病理變化,探討誘發HO-1的表現是否具有保護作用及其作用機制。Ad-hHO-1的建構,利用西方墨點法確認本研究所構築的重組腺病毒的確會表現HO-1。在膽管結紮七天的動物實驗模式,結果發現在結紮前三天給予Ad-hHO-1,可以降低血清AST活性(與膽管結紮組相較896±351 U/L v.s 450±146, p=0.01)。前一天給予腹腔注射氯化鈷亦可以降低AST活性,但不具統計意義(587±333, p=0.15)。同樣地,ALT在結紮前三天給予Ad-hHO-1較結紮組為低(999±335 U/L v.s 554±193, p=0.0135),給予氯化鈷亦可以降低ALT活性(557±177, p=0.015),顯示HO-1的給予或誘導可以減緩膽汁鬱滯肝細胞傷害及其血清中AST、ALT的濃度。總結,本實驗的結果發現利用藥物短時間誘導HO-1的表現及利用腺病毒導入HO-1基因可以減緩膽汁鬱滯所導致肝損傷。
  Cholestasis is a pathologic state of reduced bile formation or flow that occurs in many human liver diseases. Growing evidence suggests that considerable destruction of oxidative stress regulation may play an important role in cholestatic liver injury. Heme oxygenase-1 (HO-1) is the inducible and rate-limiting enzyme which catalyzes the oxidative degradation of heme. Evidence has been shown that HO-1 plays a pivotal role in anti-inflammatory, anti-apoptosis, and cytoprotective defense mechanism against oxidative stress. Elevated HO-1 expression in the liver was found in bile duct ligation aminals. However, it is not known whether the induction of HO-1 exogenously would protect the liver from damage of cholestasis. Therefore, it was the aim of the study, by the use of a bile duct-ligated model of cholestatsis in mice, to investigate the protective role of HO-1 and it’s mechanism. We constructed a human HO-1 (hHO-1) recombinant adenovirus (Ad-hHO-1) and examined the phenotypes of exogenous hHO-1 overexpression in mice with bile duct ligation (BDL). The common bile duct ligated ICR mice were pretreated with CoCl2 as a HO-1 inducer or recombinant adenovirus by intraperitoneal administration and sacrificed in 1, 3, 7, or 14 days after BDL. The HO-1 expression of Ad-hHO-1 was confirmed by western blotting. Serum levels of AST, ALT and bilirubin and the pathological changes were examined to monitor the damage in liver in BDL animal model. Compared with BDL group, the serum level of AST in Ad-hHO-1 group was decreased (896±351 U/L v.s 449±146, p=0.01) in 7 days after BDL. The ALT in Ad-hHO-1 groups was also decreased (999±335 U/L v.s. 554±193 p=0.01). Similar result of ALT level was found in BDL with CoCl2 administration (999±335 U/L v.s 557±177, p=0.015). We found that CoCl2 or Ad-hHO-1 administration could reduce the liver injury during cholesatsis and the serum levels of AST, ALT. In conclusion, HO-1 overexpression using chemical induction or adenovirus transfer could reduce the liver injury during cholestasis.
中文摘要......................................................Ⅰ
英文摘要......................................................Ⅱ
致謝..........................................................Ⅲ
總目錄........................................................Ⅳ
圖目錄........................................................Ⅵ
附錄及附表目錄................................................Ⅶ

緒論...........................................................1
材料與方法 .................................................20
A 材料..................................................20
B 方法..................................................23
1、 重組質體 pGEM-T easy/ hHO-1的構築....................23
2、 重組穿梭質體 pAdTrack-CMV/ hHO-1的構築...............23
3、 重組腺病毒pAdEasy-1/hHO-1載體的構築..................23
4、 質體製備.............................................24
5、 勝任細胞(Competent cell)的製備.......................27
6、 質體構築的相關技術...................................28
7、 質體轉入(Transformation).............................29
8、 細胞培養.............................................29
9、 重組腺病毒的擴增.....................................30
10、 重組腺病毒的定量.....................................31
11、 硫酸十二酯一聚丙醯胺凝膠電泳法(SDS-PAGE).............32
12、 西方墨點法(Western blot).............................34
13、 動物實驗之設計與分組.................................36
14、 實驗動物之血清生化測定...............................37
15、 小鼠肝臟Cytosols / microsomes 製備...................37
16、 蛋白質濃度測定.......................................38
17、 血基質氧化酵素活性測定...............................39
18、 石蠟包埋組織切片蘇木紫-伊紅染色......................41
19、 細胞凋亡之DNA 片段偵測(TUNEL assay)..................42
20、 統計方法.............................................44

結果………………………………………………………………………… 45
討論………………………………………………………………………… 53
總結………………………………………………………………………… 61
參考文獻…………………………………………………………………… 62
圖…………………………………………………………………………… 74
附錄………………………………………………………………………… 93
附表………………………………………………………………………… 95
1.陳景德: 肝膽疾病學. 1974.
2.Jaeschke H, Gores GJ, Cederbaum AI, Hinson JA, Pessayre D, Lemasters JJ: Mechanisms of hepatotoxicity. Toxicol Sci 2002, 65(2):166-176.
3.Patel T, Roberts LR, Jones BA, Gores GJ: Dysregulation of apoptosis as a mechanism of liver disease: an overview. Semin Liver Dis 1998, 18(2):105-114.
4.Rodrigues CM, Fan G, Ma X, Kren BT, Steer CJ: A novel role for ursodeoxycholic acid in inhibiting apoptosis by modulating mitochondrial membrane perturbation. J Clin Invest 1998, 101(12):2790-2799.
5.Strautnieks SS, Bull LN, Knisely AS, Kocoshis SA, Dahl N, Arnell H, Sokal E, Dahan K, Childs S, Ling V et al: A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis. Nat Genet 1998, 20(3):233-238.
6.Patel T, Bronk SF, Gores GJ: Increases of intracellular magnesium promote glycodeoxycholate-induced apoptosis in rat hepatocytes. J Clin Invest 1994, 94(6):2183-2192.
7.Kerr JF, Wyllie AH, Currie AR: Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 1972, 26(4):239-257.
8.Wyllie AH, Morris RG, Smith AL, Dunlop D: Chromatin cleavage in apoptosis: association with condensed chromatin morphology and dependence on macromolecular synthesis. J Pathol 1984, 142(1):67-77.
9.Green DR: Apoptotic pathways: the roads to ruin. Cell 1998, 94(6):695-698.
10.Faubion WA, Gores GJ: Death receptors in liver biology and pathobiology. Hepatology 1999, 29(1):1-4.
11.Faubion WA, Guicciardi ME, Miyoshi H, Bronk SF, Roberts PJ, Svingen PA, Kaufmann SH, Gores GJ: Toxic bile salts induce rodent hepatocyte apoptosis via direct activation of Fas. J Clin Invest 1999, 103(1):137-145.
12.Miyoshi H, Rust C, Roberts PJ, Burgart LJ, Gores GJ: Hepatocyte apoptosis after bile duct ligation in the mouse involves Fas. Gastroenterology 1999, 117(3):669-677.
13.Sodeman T, Bronk SF, Roberts PJ, Miyoshi H, Gores GJ: Bile salts mediate hepatocyte apoptosis by increasing cell surface trafficking of Fas. Am J Physiol Gastrointest Liver Physiol 2000, 278(6):G992-999.
14.Jaeschke H, Smith CW: Mechanisms of neutrophil-induced parenchymal cell injury. J Leukoc Biol 1997, 61(6):647-653.
15.Jaeschke H, Smith CW, Clemens MG, Ganey PE, Roth RA: Mechanisms of inflammatory liver injury: adhesion molecules and cytotoxicity of neutrophils. Toxicol Appl Pharmacol 1996, 139(2):213-226.
16.Laskin DL, Laskin JD: Role of macrophages and inflammatory mediators in chemically induced toxicity. Toxicology 2001, 160(1-3):111-118.
17.Lawson JA, Farhood A, Hopper RD, Bajt ML, Jaeschke H: The hepatic inflammatory response after acetaminophen overdose: role of neutrophils. Toxicol Sci 2000, 54(2):509-516.
18.Maher JJ, Scott MK, Saito JM, Burton MC: Adenovirus-mediated expression of cytokine-induced neutrophil chemoattractant in rat liver induces a neutrophilic hepatitis. Hepatology 1997, 25(3):624-630.
19.Jaeschke H: Cellular adhesion molecules: regulation and functional significance in the pathogenesis of liver diseases. Am J Physiol 1997, 273(3 Pt 1):G602-611.
20.Chosay JG, Essani NA, Dunn CJ, Jaeschke H: Neutrophil margination and extravasation in sinusoids and venules of liver during endotoxin-induced injury. Am J Physiol 1997, 272(5 Pt 1):G1195-1200.
21.Essani NA, Fisher MA, Farhood A, Manning AM, Smith CW, Jaeschke H: Cytokine-induced upregulation of hepatic intercellular adhesion molecule-1 messenger RNA expression and its role in the pathophysiology of murine endotoxin shock and acute liver failure. Hepatology 1995, 21(6):1632-1639.
22.Essani NA, Bajt ML, Farhood A, Vonderfecht SL, Jaeschke H: Transcriptional activation of vascular cell adhesion molecule-1 gene in vivo and its role in the pathophysiology of neutrophil-induced liver injury in murine endotoxin shock. J Immunol 1997, 158(12):5941-5948.
23.Lawson JA, Burns AR, Farhood A, Lynn Bajt M, Collins RG, Smith CW, Jaeschke H: Pathophysiologic importance of E- and L-selectin for neutrophil-induced liver injury during endotoxemia in mice. Hepatology 2000, 32(5):990-998.
24.Jaeschke H, Farhood A, Bautista AP, Spolarics Z, Spitzer JJ, Smith CW: Functional inactivation of neutrophils with a Mac-1 (CD11b/CD18) monoclonal antibody protects against ischemia-reperfusion injury in rat liver. Hepatology 1993, 17(5):915-923.
25.Curzio M, Esterbauer H, Di Mauro C, Cecchini G, Dianzani MU: Chemotactic activity of the lipid peroxidation product 4-hydroxynonenal and homologous hydroxyalkenals. Biol Chem Hoppe Seyler 1986, 367(4):321-329.
26.Liu P, Vonderfecht SL, McGuire GM, Fisher MA, Farhood A, Jaeschke H: The 21-aminosteroid tirilazad mesylate protects against endotoxin shock and acute liver failure in rats. J Pharmacol Exp Ther 1994, 271(1):438-445.
27.Jaeschke H, Ho YS, Fisher MA, Lawson JA, Farhood A: Glutathione peroxidase-deficient mice are more susceptible to neutrophil-mediated hepatic parenchymal cell injury during endotoxemia: importance of an intracellular oxidant stress. Hepatology 1999, 29(2):443-450.
28.Jaeschke H: Reactive oxygen and mechanisms of inflammatory liver injury. J Gastroenterol Hepatol 2000, 15(7):718-724.
29.Fubini B, Hubbard A: Reactive oxygen species (ROS) and reactive nitrogen species (RNS) generation by silica in inflammation and fibrosis. Free Radic Biol Med 2003, 34(12):1507-1516.
30.Armstrong D: Free radical and antioxidant protocols. Introduction. Methods Mol Biol 1998, 108:v-viii.
31.Halliwell B: Oxygen and nitrogen are pro-carcinogens. Damage to DNA by reactive oxygen, chlorine and nitrogen species: measurement, mechanism and the effects of nutrition. Mutat Res 1999, 443(1-2):37-52.
32.Vertuani S, Angusti A, Manfredini S: The antioxidants and pro-antioxidants network: an overview. Curr Pharm Des 2004, 10(14):1677-1694.
33.Cai J, Jones DP: Superoxide in apoptosis. Mitochondrial generation triggered by cytochrome c loss. J Biol Chem 1998, 273(19):11401-11404.
34.Wong GH, Elwell JH, Oberley LW, Goeddel DV: Manganous superoxide dismutase is essential for cellular resistance to cytotoxicity of tumor necrosis factor. Cell 1989, 58(5):923-931.
35.Mayer M, Noble M: N-acetyl-L-cysteine is a pluripotent protector against cell death and enhancer of trophic factor-mediated cell survival in vitro. Proc Natl Acad Sci U S A 1994, 91(16):7496-7500.
36.Liu TZ, Lee KT, Chern CL, Cheng JT, Stern A, Tsai LY: Free radical-triggered hepatic injury of experimental obstructive jaundice of rats involves overproduction of proinflammatory cytokines and enhanced activation of nuclear factor kappaB. Ann Clin Lab Sci 2001, 31(4):383-390.
37.Yerushalmi B, Dahl R, Devereaux MW, Gumpricht E, Sokol RJ: Bile acid-induced rat hepatocyte apoptosis is inhibited by antioxidants and blockers of the mitochondrial permeability transition. Hepatology 2001, 33(3):616-626.
38.Padillo FJ, Cruz A, Navarrete C, Bujalance I, Briceno J, Gallardo JI, Marchal T, Caballero R, Tunez I, Muntane J et al: Melatonin prevents oxidative stress and hepatocyte cell death induced by experimental cholestasis. Free Radic Res 2004, 38(7):697-704.
39.Cruz A, Padillo FJ, Tunez I, Munoz C, Granados J, Pera-Madrazo C, Montilla P: Melatonin protects against renal oxidative stress after obstructive jaundice in rats. Eur J Pharmacol 2001, 425(2):135-139.
40.Wise C, Drabkin D: Degradation of haemoglobin and hemin to biliverdin by a new cell-free system obtained from the hemophagous organ of dog placenta. Fed Proc 1964, 23:323.
41.Tenhunen R, Marver HS, Schmid R: The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase. Proc Natl Acad Sci U S A 1968, 61(2):748-755.
42.Tenhunen R, Marver HS, Schmid R: Microsomal heme oxygenase. Characterization of the enzyme. J Biol Chem 1969, 244(23):6388-6394.
43.Tenhunen R, Marver HS, Schmid R: The enzymatic conversion of hemoglobin to bilirubin. Trans Assoc Am Physicians 1969, 82:363-371.
44.Keyse SM, Tyrrell RM: Heme oxygenase is the major 32-kDa stress protein induced in human skin fibroblasts by UVA radiation, hydrogen peroxide, and sodium arsenite. Proc Natl Acad Sci U S A 1989, 86(1):99-103.
45.Morse D, Choi AM: Heme oxygenase-1: the "emerging molecule" has arrived. Am J Respir Cell Mol Biol 2002, 27(1):8-16.
46.Oberle S, Schwartz P, Abate A, Schroder H: The antioxidant defense protein ferritin is a novel and specific target for pentaerithrityl tetranitrate in endothelial cells. Biochem Biophys Res Commun 1999, 261(1):28-34.
47.Otterbein LE, Choi AM: Heme oxygenase: colors of defense against cellular stress. Am J Physiol Lung Cell Mol Physiol 2000, 279(6):L1029-1037.
48.Otterbein LE, Bach FH, Alam J, Soares M, Tao Lu H, Wysk M, Davis RJ, Flavell RA, Choi AM: Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway. Nat Med 2000, 6(4):422-428.
49.Yesilkaya A, Altinayak R, Korgun DK: The antioxidant effect of free bilirubin on cumene-hydroperoxide treated human leukocytes. Gen Pharmacol 2000, 35(1):17-20.
50.Marks GS, Brien JF, Nakatsu K, McLaughlin BE: Does carbon monoxide have a physiological function? Trends Pharmacol Sci 1991, 12(5):185-188.
51.Verma A, Hirsch DJ, Glatt CE, Ronnett GV, Snyder SH: Carbon monoxide: a putative neural messenger. Science 1993, 259(5093):381-384.
52.Maines M: Carbon monoxide: An emerging regulator of cGMP in the brain. Mol Cell Neurosci 1993, 4:389-397.
53.Furchgott RF, Jothianandan D: Endothelium-dependent and -independent vasodilation involving cyclic GMP: relaxation induced by nitric oxide, carbon monoxide and light. Blood Vessels 1991, 28(1-3):52-61.
54.Motterlini R, Gonzales A, Foresti R, Clark JE, Green CJ, Winslow RM: Heme oxygenase-1-derived carbon monoxide contributes to the suppression of acute hypertensive responses in vivo. Circ Res 1998, 83(5):568-577.
55.Brouard S, Otterbein LE, Anrather J, Tobiasch E, Bach FH, Choi AM, Soares MP: Carbon monoxide generated by heme oxygenase 1 suppresses endothelial cell apoptosis. J Exp Med 2000, 192(7):1015-1026.
56.Stocker R, Yamamoto Y, McDonagh AF, Glazer AN, Ames BN: Bilirubin is an antioxidant of possible physiological importance. Science 1987, 235(4792):1043-1046.
57.Clark JE, Foresti R, Sarathchandra P, Kaur H, Green CJ, Motterlini R: Heme oxygenase-1-derived bilirubin ameliorates postischemic myocardial dysfunction. Am J Physiol Heart Circ Physiol 2000, 278(2):H643-651.
58.Vachharajani TJ, Work J, Issekutz AC, Granger DN: Heme oxygenase modulates selectin expression in different regional vascular beds. Am J Physiol Heart Circ Physiol 2000, 278(5):H1613-1617.
59.Vile GF, Tyrrell RM: Oxidative stress resulting from ultraviolet A irradiation of human skin fibroblasts leads to a heme oxygenase-dependent increase in ferritin. J Biol Chem 1993, 268(20):14678-14681.
60.Eisenstein RS, Garcia-Mayol D, Pettingell W, Munro HN: Regulation of ferritin and heme oxygenase synthesis in rat fibroblasts by different forms of iron. Proc Natl Acad Sci U S A 1991, 88(3):688-692.
61.Balla G, Jacob HS, Balla J, Rosenberg M, Nath K, Apple F, Eaton JW, Vercellotti GM: Ferritin: a cytoprotective antioxidant strategem of endothelium. J Biol Chem 1992, 267(25):18148-18153.
62.McCoubrey WK, Jr., Huang TJ, Maines MD: Heme oxygenase-2 is a hemoprotein and binds heme through heme regulatory motifs that are not involved in heme catalysis. J Biol Chem 1997, 272(19):12568-12574.
63.Hayashi S, Omata Y, Sakamoto H, Higashimoto Y, Hara T, Sagara Y, Noguchi M: Characterization of rat heme oxygenase-3 gene. Implication of processed pseudogenes derived from heme oxygenase-2 gene. Gene 2004, 336(2):241-250.
64.Maines MD: The heme oxygenase system: a regulator of second messenger gases. Annu Rev Pharmacol Toxicol 1997, 37:517-554.
65.Yachie A, Niida Y, Wada T, Igarashi N, Kaneda H, Toma T, Ohta K, Kasahara Y, Koizumi S: Oxidative stress causes enhanced endothelial cell injury in human heme oxygenase-1 deficiency. J Clin Invest 1999, 103(1):129-135.
66.Poss KD, Tonegawa S: Reduced stress defense in heme oxygenase 1-deficient cells. Proc Natl Acad Sci U S A 1997, 94(20):10925-10930.
67.Lee TS, Chau LY: Heme oxygenase-1 mediates the anti-inflammatory effect of interleukin-10 in mice. Nat Med 2002, 8(3):240-246.
68.Inoue S, Suzuki M, Nagashima Y, Suzuki S, Hashiba T, Tsuburai T, Ikehara K, Matsuse T, Ishigatsubo Y: Transfer of heme oxygenase 1 cDNA by a replication-deficient adenovirus enhances interleukin 10 production from alveolar macrophages that attenuates lipopolysaccharide-induced acute lung injury in mice. Hum Gene Ther 2001, 12(8):967-979.
69.Hashiba T, Suzuki M, Nagashima Y, Suzuki S, Inoue S, Tsuburai T, Matsuse T, Ishigatubo Y: Adenovirus-mediated transfer of heme oxygenase-1 cDNA attenuates severe lung injury induced by the influenza virus in mice. Gene Ther 2001, 8(19):1499-1507.
70.Soares MP, Lin Y, Anrather J, Csizmadia E, Takigami K, Sato K, Grey ST, Colvin RB, Choi AM, Poss KD et al: Expression of heme oxygenase-1 can determine cardiac xenograft survival. Nat Med 1998, 4(9):1073-1077.
71.Christou H, Morita T, Hsieh CM, Koike H, Arkonac B, Perrella MA, Kourembanas S: Prevention of hypoxia-induced pulmonary hypertension by enhancement of endogenous heme oxygenase-1 in the rat. Circ Res 2000, 86(12):1224-1229.
72.Minamino T, Christou H, Hsieh CM, Liu Y, Dhawan V, Abraham NG, Perrella MA, Mitsialis SA, Kourembanas S: Targeted expression of heme oxygenase-1 prevents the pulmonary inflammatory and vascular responses to hypoxia. Proc Natl Acad Sci U S A 2001, 98(15):8798-8803.
73.Lai IR, Ma MC, Chen CF, Chang KJ: The protective role of heme oxygenase-1 on the liver after hypoxic preconditioning in rats. Transplantation 2004, 77(7):1004-1008.
74.Yet SF, Tian R, Layne MD, Wang ZY, Maemura K, Solovyeva M, Ith B, Melo LG, Zhang L, Ingwall JS et al: Cardiac-specific expression of heme oxygenase-1 protects against ischemia and reperfusion injury in transgenic mice. Circ Res 2001, 89(2):168-173.
75.Wang XH, Wang K, Zhang F, Li XC, Qian XF, Cheng F, Li GQ, Fan Y: Alleviating ischemia-reperfusion injury in aged rat liver by induction of heme oxygenase-1. Transplant Proc 2004, 36(10):2917-2923.
76.Amersi F, Buelow R, Kato H, Ke B, Coito AJ, Shen XD, Zhao D, Zaky J, Melinek J, Lassman CR et al: Upregulation of heme oxygenase-1 protects genetically fat Zucker rat livers from ischemia/reperfusion injury. J Clin Invest 1999, 104(11):1631-1639.
77.Elbirt KK, Bonkovsky HL: Heme oxygenase: recent advances in understanding its regulation and role. Proc Assoc Am Physicians 1999, 111(5):438-447.
78.Lavrovsky Y, Schwartzman ML, Levere RD, Kappas A, Abraham NG: Identification of binding sites for transcription factors NF-kappa B and AP-2 in the promoter region of the human heme oxygenase 1 gene. Proc Natl Acad Sci U S A 1994, 91(13):5987-5991.
79.Choi AM, Alam J: Heme oxygenase-1: function, regulation, and implication of a novel stress-inducible protein in oxidant-induced lung injury. Am J Respir Cell Mol Biol 1996, 15(1):9-19.
80.Alam J, Cai J, Smith A: Isolation and characterization of the mouse heme oxygenase-1 gene. Distal 5' sequences are required for induction by heme or heavy metals. J Biol Chem 1994, 269(2):1001-1009.
81.Camhi SL, Alam J, Otterbein L, Sylvester SL, Choi AM: Induction of heme oxygenase-1 gene expression by lipopolysaccharide is mediated by AP-1 activation. Am J Respir Cell Mol Biol 1995, 13(4):387-398.
82.Lee PJ, Alam J, Sylvester SL, Inamdar N, Otterbein L, Choi AM: Regulation of heme oxygenase-1 expression in vivo and in vitro in hyperoxic lung injury. Am J Respir Cell Mol Biol 1996, 14(6):556-568.
83.Lee PJ, Camhi SL, Chin BY, Alam J, Choi AM: AP-1 and STAT mediate hyperoxia-induced gene transcription of heme oxygenase-1. Am J Physiol Lung Cell Mol Physiol 2000, 279(1):L175-182.
84.Rensing H, Jaeschke H, Bauer I, Patau C, Datene V, Pannen BH, Bauer M: Differential activation pattern of redox-sensitive transcription factors and stress-inducible dilator systems heme oxygenase-1 and inducible nitric oxide synthase in hemorrhagic and endotoxic shock. Crit Care Med 2001, 29(10):1962-1971.
85.Brand K, Page S, Walli AK, Neumeier D, Baeuerle PA: Role of nuclear factor-kappa B in atherogenesis. Exp Physiol 1997, 82(2):297-304.
86.Liao F, Andalibi A, deBeer FC, Fogelman AM, Lusis AJ: Genetic control of inflammatory gene induction and NF-kappa B-like transcription factor activation in response to an atherogenic diet in mice. J Clin Invest 1993, 91(6):2572-2579.
87.Alam J, Stewart D, Touchard C, Boinapally S, Choi AM, Cook JL: Nrf2, a Cap'n'Collar transcription factor, regulates induction of the heme oxygenase-1 gene. J Biol Chem 1999, 274(37):26071-26078.
88.Alam J, Wicks C, Stewart D, Gong P, Touchard C, Otterbein S, Choi AM, Burow ME, Tou J: Mechanism of heme oxygenase-1 gene activation by cadmium in MCF-7 mammary epithelial cells. Role of p38 kinase and Nrf2 transcription factor. J Biol Chem 2000, 275(36):27694-27702.
89.He CH, Gong P, Hu B, Stewart D, Choi ME, Choi AM, Alam J: Identification of activating transcription factor 4 (ATF4) as an Nrf2-interacting protein. Implication for heme oxygenase-1 gene regulation. J Biol Chem 2001, 276(24):20858-20865.
90.Elbirt KK, Whitmarsh AJ, Davis RJ, Bonkovsky HL: Mechanism of sodium arsenite-mediated induction of heme oxygenase-1 in hepatoma cells. Role of mitogen-activated protein kinases. J Biol Chem 1998, 273(15):8922-8931.
91.Zhang X, Bedard EL, Potter R, Zhong R, Alam J, Choi AM, Lee PJ: Mitogen-activated protein kinases regulate HO-1 gene transcription after ischemia-reperfusion lung injury. Am J Physiol Lung Cell Mol Physiol 2002, 283(4):L815-829.
92.Ryter SW, Xi S, Hartsfield CL, Choi AM: Mitogen activated protein kinase (MAPK) pathway regulates heme oxygenase-1 gene expression by hypoxia in vascular cells. Antioxid Redox Signal 2002, 4(4):587-592.
93.Terry CM, Clikeman JA, Hoidal JR, Callahan KS: TNF-alpha and IL-1alpha induce heme oxygenase-1 via protein kinase C, Ca2+, and phospholipase A2 in endothelial cells. Am J Physiol 1999, 276(5 Pt 2):H1493-1501.
94.Santoro MG: Heat shock factors and the control of the stress response. Biochem Pharmacol 2000, 59(1):55-63.
95.Morimoto RI, Santoro MG: Stress-inducible responses and heat shock proteins: new pharmacologic targets for cytoprotection. Nat Biotechnol 1998, 16(9):833-838.
96.Petrache I, Otterbein LE, Alam J, Wiegand GW, Choi AM: Heme oxygenase-1 inhibits TNF-alpha-induced apoptosis in cultured fibroblasts. Am J Physiol Lung Cell Mol Physiol 2000, 278(2):L312-319.
97.Dore S, Takahashi M, Ferris CD, Zakhary R, Hester LD, Guastella D, Snyder SH: Bilirubin, formed by activation of heme oxygenase-2, protects neurons against oxidative stress injury. Proc Natl Acad Sci U S A 1999, 96(5):2445-2450.
98.Tobiasch E, Gunther L, Bach FH: Heme oxygenase-1 protects pancreatic beta cells from apoptosis caused by various stimuli. J Investig Med 2001, 49(6):566-571.
99.Brouard S, Berberat PO, Tobiasch E, Seldon MP, Bach FH, Soares MP: Heme oxygenase-1-derived carbon monoxide requires the activation of transcription factor NF-kappa B to protect endothelial cells from tumor necrosis factor-alpha-mediated apoptosis. J Biol Chem 2002, 277(20):17950-17961.
100.Duckers HJ, Boehm M, True AL, Yet SF, San H, Park JL, Clinton Webb R, Lee ME, Nabel GJ, Nabel EG: Heme oxygenase-1 protects against vascular constriction and proliferation. Nat Med 2001, 7(6):693-698.
101.Inguaggiato P, Gonzalez-Michaca L, Croatt AJ, Haggard JJ, Alam J, Nath KA: Cellular overexpression of heme oxygenase-1 up-regulates p21 and confers resistance to apoptosis. Kidney Int 2001, 60(6):2181-2191.
102.Polyak K, Waldman T, He TC, Kinzler KW, Vogelstein B: Genetic determinants of p53-induced apoptosis and growth arrest. Genes Dev 1996, 10(15):1945-1952.
103.Megyesi J, Safirstein RL, Price PM: Induction of p21WAF1/CIP1/SDI1 in kidney tubule cells affects the course of cisplatin-induced acute renal failure. J Clin Invest 1998, 101(4):777-782.
104.Sikorski EM, Hock T, Hill-Kapturczak N, Agarwal A: The story so far: Molecular regulation of the heme oxygenase-1 gene in renal injury. Am J Physiol Renal Physiol 2004, 286(3):F425-441.
105.Nath KA, Balla G, Vercellotti GM, Balla J, Jacob HS, Levitt MD, Rosenberg ME: Induction of heme oxygenase is a rapid, protective response in rhabdomyolysis in the rat. J Clin Invest 1992, 90(1):267-270.
106.Nimura T, Weinstein PR, Massa SM, Panter S, Sharp FR: Heme oxygenase-1 (HO-1) protein induction in rat brain following focal ischemia. Brain Res Mol Brain Res 1996, 37(1-2):201-208.
107.Panahian N, Yoshiura M, Maines MD: Overexpression of heme oxygenase-1 is neuroprotective in a model of permanent middle cerebral artery occlusion in transgenic mice. J Neurochem 1999, 72(3):1187-1203.
108.Stewart PL, Fuller SD, Burnett RM: Difference imaging of adenovirus: bridging the resolution gap between X-ray crystallography and electron microscopy. Embo J 1993, 12(7):2589-2599.
109.Bramson JL, Graham FL, Gauldie J: The use of adenoviral vectors for gene therapy and gene transfer in vivo. Curr Opin Biotechnol 1995, 6(5):590-595.
110.Greber UF, Willetts M, Webster P, Helenius A: Stepwise dismantling of adenovirus 2 during entry into cells. Cell 1993, 75(3):477-486.
111.Moran E: Interaction of adenoviral proteins with pRB and p53. Faseb J 1993, 7(10):880-885.
112.Haddada H, Cordier L, Perricaudet M: Gene therapy using adenovirus vectors. Curr Top Microbiol Immunol 1995, 199 (Pt 3):297-306.
113.He TC, Zhou S, da Costa LT, Yu J, Kinzler KW, Vogelstein B: A simplified system for generating recombinant adenoviruses. Proc Natl Acad Sci U S A 1998, 95(5):2509-2514.
114.McGrory WJ, Bautista DS, Graham FL: A simple technique for the rescue of early region I mutations into infectious human adenovirus type 5. Virology 1988, 163(2):614-617.
115.Weatherall DJ: Scope and limitations of gene therapy. Br Med Bull 1995, 51(1):1-11.
116.Robbins PD, Ghivizzani SC: Viral vectors for gene therapy. Pharmacol Ther 1998, 80(1):35-47.
117.Ish-Horowicz D, Burke JF: Rapid and efficient cosmid cloning. Nucleic Acids Res 1981, 9(13):2989-2998.
118.Towbin H, Staehelin T, Gordon J: Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A 1979, 76(9):4350-4354.
119.Kountouras J, Billing BH, Scheuer PJ: Prolonged bile duct obstruction: a new experimental model for cirrhosis in the rat. Br J Exp Pathol 1984, 65(3):305-311.
120.Graham FL, Smiley J, Russell WC, Nairn R: Characteristics of a human cell line transformed by DNA from human adenovirus type 5. J Gen Virol 1977, 36(1):59-74.
121.Dai J, Rabie AB, Hagg U, Xu R: Alternative gene therapy strategies for the repair of craniofacial bone defects. Curr Gene Ther 2004, 4(4):469-485.
122.Cao B, Mytinger JR, Huard J: Adenovirus mediated gene transfer to skeletal muscle. Microsc Res Tech 2002, 58(1):45-51.
123.Juan SH, Lee TS, Tseng KW, Liou JY, Shyue SK, Wu KK, Chau LY: Adenovirus-mediated heme oxygenase-1 gene transfer inhibits the development of atherosclerosis in apolipoprotein E-deficient mice. Circulation 2001, 104(13):1519-1525.
124.Jooss K, Chirmule N: Immunity to adenovirus and adeno-associated viral vectors: implications for gene therapy. Gene Ther 2003, 10(11):955-963.
125.Volpers C, Kochanek S: Adenoviral vectors for gene transfer and therapy. J Gene Med 2004, 6 Suppl 1:S164-171.
126.Ilan Y, Saito H, Thummala NR, Chowdhury NR: Adenovirus-mediated gene therapy of liver diseases. Semin Liver Dis 1999, 19(1):49-59.
127.Bergelson JM, Cunningham JA, Droguett G, Kurt-Jones EA, Krithivas A, Hong JS, Horwitz MS, Crowell RL, Finberg RW: Isolation of a common receptor for Coxsackie B viruses and adenoviruses 2 and 5. Science 1997, 275(5304):1320-1323.
128.Wickham TJ, Mathias P, Cheresh DA, Nemerow GR: Integrins alpha v beta 3 and alpha v beta 5 promote adenovirus internalization but not virus attachment. Cell 1993, 73(2):309-319.
129.Smith T, Idamakanti N, Kylefjord H, Rollence M, King L, Kaloss M, Kaleko M, Stevenson SC: In vivo hepatic adenoviral gene delivery occurs independently of the coxsackievirus-adenovirus receptor. Mol Ther 2002, 5(6):770-779.
130.Einfeld DA, Schroeder R, Roelvink PW, Lizonova A, King CR, Kovesdi I, Wickham TJ: Reducing the native tropism of adenovirus vectors requires removal of both CAR and integrin interactions. J Virol 2001, 75(23):11284-11291.
131.Martin K, Brie A, Saulnier P, Perricaudet M, Yeh P, Vigne E: Simultaneous CAR- and alpha V integrin-binding ablation fails to reduce Ad5 liver tropism. Mol Ther 2003, 8(3):485-494.
132.Dechecchi MC, Melotti P, Bonizzato A, Santacatterina M, Chilosi M, Cabrini G: Heparan sulfate glycosaminoglycans are receptors sufficient to mediate the initial binding of adenovirus types 2 and 5. J Virol 2001, 75(18):8772-8780.
133.Dechecchi MC, Tamanini A, Bonizzato A, Cabrini G: Heparan sulfate glycosaminoglycans are involved in adenovirus type 5 and 2-host cell interactions. Virology 2000, 268(2):382-390.
134.Cichon G, Boeckh-Herwig S, Kuemin D, Hoffmann C, Schmidt HH, Wehnes E, Haensch W, Schneider U, Eckhardt U, Burger R et al: Titer determination of Ad5 in blood: a cautionary note. Gene Ther 2003, 10(12):1012-1017.
135.Sokol RJ, Winklhofer-Roob BM, Devereaux MW, McKim JM, Jr.: Generation of hydroperoxides in isolated rat hepatocytes and hepatic mitochondria exposed to hydrophobic bile acids. Gastroenterology 1995, 109(4):1249-1256.
136.Pastor A, Collado PS, Almar M, Gonzalez-Gallego J: Antioxidant enzyme status in biliary obstructed rats: effects of N-acetylcysteine. J Hepatol 1997, 27(2):363-370.
137.Alptekin N, Mehmetcik G, Uysal M, Aykac-toker G: Evidence for oxidative stress in the hepatic mitochondria of bile duct ligated rats. Pharmacol Res 1997, 36(3):243-247.
138.Brasile L, Buelow R, Stubenitsky BM, Kootstra G: Induction of heme oxygenase-1 in kidneys during ex vivo warm perfusion. Transplantation 2003, 76(8):1145-1149.
139.Abraham NG, Kappas A: Heme oxygenase and the cardiovascular-renal system. Free Radic Biol Med 2005, 39(1):1-25.
140.Tephly TR, Hasegawa E, Baron J: Effect of drugs on heme synthesis in the liver. Metabolism 1971, 20(2):200-214.
141.Redaelli CA, Tian YH, Schaffner T, Ledermann M, Baer HU, Dufour JF: Extended preservation of rat liver graft by induction of heme oxygenase-1. Hepatology 2002, 35(5):1082-1092.
142.Dorman RB, Bajt ML, Farhood A, Mayes J, Jaeschke H: Heme oxygenase-1 induction in hepatocytes and non-parenchymal cells protects against liver injury during endotoxemia. Comp Hepatol 2004, 3 Suppl 1:S42.
143.Tsai LY, Lee KT, Liu TZ: Evidence for accelerated generation of hydroxyl radicals in experimental obstructive jaundice of rats. Free Radic Biol Med 1998, 24(5):732-737.
144.Akagi K, Sandig V, Vooijs M, Van der Valk M, Giovannini M, Strauss M, Berns A: Cre-mediated somatic site-specific recombination in mice. Nucleic Acids Res 1997, 25(9):1766-1773.
145.Yang Y, Jooss KU, Su Q, Ertl HC, Wilson JM: Immune responses to viral antigens versus transgene product in the elimination of recombinant adenovirus-infected hepatocytes in vivo. Gene Ther 1996, 3(2):137-144.
146.Rodrigues CM, Fan G, Wong PY, Kren BT, Steer CJ: Ursodeoxycholic acid may inhibit deoxycholic acid-induced apoptosis by modulating mitochondrial transmembrane potential and reactive oxygen species production. Mol Med 1998, 4(3):165-178.
147.Sass G, Soares MC, Yamashita K, Seyfried S, Zimmermann WH, Eschenhagen T, Kaczmarek E, Ritter T, Volk HD, Tiegs G: Heme oxygenase-1 and its reaction product, carbon monoxide, prevent inflammation-related apoptotic liver damage in mice. Hepatology 2003, 38(4):909-918.
148.Ding WX, Yin XM: Dissection of the multiple mechanisms of TNF-alpha-induced apoptosis in liver injury. J Cell Mol Med 2004, 8(4):445-454.
149.Heneghan MA, Harrison PM: Pathogenesis of ascites in cirrhosis and portal hypertension. Med Sci Monit 2000, 6(4):807-816.
150.Mancinella A: [The hepatorenal syndrome: etiopathogenetic, clinical and therapeutic considerations]. Clin Ter 1976, 79(6):583-590.
151.Gaines DI, Fallon MB: Hepatopulmonary syndrome. Liver Int 2004, 24(5):397-401.
152.Miyazono M, Garat C, Morris KG, Jr., Carter EP: Decreased renal heme oxygenase-1 expression contributes to decreased renal function during cirrhosis. Am J Physiol Renal Physiol 2002, 283(5):F1123-1131.
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