請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/28180完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 林君榮(Chun-Jung Lin) | |
| dc.contributor.author | Jing-Shan Wu | en |
| dc.contributor.author | 吳菁山 | zh_TW |
| dc.date.accessioned | 2021-06-13T00:02:15Z | - |
| dc.date.available | 2007-08-08 | |
| dc.date.copyright | 2007-08-08 | |
| dc.date.issued | 2007 | |
| dc.date.submitted | 2007-07-31 | |
| dc.identifier.citation | Aranda A and Pascual A. Nuclear hormone receptors and gene expression. Physiol Rev 2001; 81:1269-1304.
Argaud D, Halimi S, Catelloni F and Leverve XM. Inhibition of gluconeogenesis in isolated rat hepatocytes after chronic treatment with Phenobarbital. Biochem J 1991;280:663–669. Abbud W, Habinowski S, Zhang JZ, Kendrew J, Elkairi FS, Kemp BE, Witters LA and Ismail-Beigi F. Stimulation of AMP-activated protein kinase (AMPK) is associated with enhancement of Glut1-mediated glucose transport. Arch Biochem Biophys 2000; 380:347-352. Bertilsson G, Heidrich J, Svensson K, Asman M, Jendeberg L, Sydow-Backman M, Ohlsson R, Postlind H, Blomquist P and Berkenstam A Identification of a human nuclear receptor defines a new signaling pathway for CYP3A induction. Proc Natl Acad Sci USA 1998; 95:12208-12213. Barthel A, Schmoll D and Unterman TG. FoxO proteins in insulin action and metabolism. Trends Endocrinol Metab 2005; 16:183–189. Bilger A, Bennett LM, Carabeo RA, Chiaverotti TA, Dvorak C, Liss, KM, Schadewald, SA, Pitot, HC and Drinkwater NR. A potent modifier of liver cancer risk on distal mouse chromosome 1: linkage analysis and characterization of congenic lines. Genetics 2004; 167:859–866. Bergeron R, Previs SF, Cline GW, Perret P, Russell RR III, Young LH and Shulman GI. Effect 5-aminoimidazole-4-carboxamide-1-beta- D- ribofuranoside infusion on in vivo glucose and lipid metabolism in lean and obese Zucker rats. Diabetes 2001; 50:1076–1082. Blond JL, Lavillette D, Cheynet V, Bouton O, Oriol G, Chapel-Fernandes S, Mandrand B, Mallet F and Cosset FL. An envelope glycoprotein of the human endogenous retrovirus HERV-W is expressed in the human placenta and fuses cells expressing the type D mammalian retrovirus receptor. J viol 2000; 74: 3321-3329. Blättler SM, Rencurel F, Kaufmann MR, and Meyer UA. In the regulation of cytochrome P450 genes, phenobarbital targets LKB1 for necessary activation of AMP-activated protein kinase. Proc. Natl. Acad. Sci. U.S.A 2007; 104:1045-1050. Burant CF and Bell GI. Mammalian facilitative glucose transporters: evidence for similar substrate recognition sites in functionally monomeric proteins. Biochemistry. 1992; 31:10414-20. Chawla A, Joyce JR, Ronald ME and David JM. Nuclear receptors and lipid physiology : opening the x-files. Science 2001; 294:1866-1870. Claudel T, Staels B and Kuipers F. The Farnesoid X Receptor: A Molecular Link Between Bile Acid and Lipid and Glucose Metabolism. Arterioscler Thromb Vasc Biol 2005; 25:2020 - 2030. Carling D. The AMP-activated protein kinase cascade—a unifying system for energy control. Trends Biochem Sci 2004; 29:18–24. Clarson LH, Glazier JD, Sides MK and Sibley CP. Expression of the facilitated glucose transporters (GLUT1 and GLUT3) by a choriocarcinoma cell line (JAr) and cytotrophoblast cells in culture. Placenta 1997; 18:333–340. Chang KW, Yang PY, Lai HY, Yeh TS, Chen TC and Yeh CT. Identification of a novel actin isoform in hepatocellular carcinoma. Hepatol Res. 2006; 36: 33-39. Chen CP, Wang KG, Chen CY, Yu C, Chuang HC and Chen H. Altered placental syncytin and its receptor ASCT2 expression in placental development and pre-eclampsia. BJOG 2006; 113:152-158. Claudel T, Sturm E, Duez H, Torra I.P, Sirvent A, Kosykh V, Fruchart JC, Dallongeville J, Hum DW, Kuipers F and Staels B. Bile acid-activated nuclear receptor FXR suppresses apolipoprotein A-I transcription via a negative FXR response element. J Clin Invest 2002; 109:961-971. Chaloin SG, Pascussi JM, Garcia LP,Daujat M, Waechter F, Fabre JM Carrère N and Maurel P. Induction of CYP2C Genes in Human Hepatocytes in Primary Culture. Drug Metab Dispos 2001; 29:242-251. Escriva H, Delaunay F and Laudet V. Ligand binding and nuclear receptor evolution. Bioessays 2000; 22:717 -727. Evans RM The steroid and thyroid hormone receptor superfamily. Science1988; 240: 889. Elwan MA, Ishii T, Sakkuragawa N. Characterization of the dopamine transporter gene expression and binding sites in cultured human amniotic epithelial cells. Neurosci Lett 2003; 342:61-64. Fujii N,, Jessen N, and Goodyear LJ. AMP-activated protein kinase and the regulation of glucose transport. Am J Physiol Endocrinol Metab 2006; 291: E867–E877. Fowden AL and Forhead AJ. Endocrine mechanisms of intrauterine programming. Reproduction 2004; 127:515 - 526. Giguere V. Orphan nuclear receptors: from gene to function. Endocr Rev 1999; 20:689 –725. Guo GL, Lambert G, Negishi M, Ward JM, Brewer HB, Jr Kliewer SA, Gonzalez FJ and Sinal CJ. Complementary roles of farnesoid X receptor, pregnane X receptor, and constitutive androstane receptor in protection against bile acid toxicity. J Biol Chem 2003; 278:45062–45071. Garcia J C, Strube M, Leingang K, Keller K and Mueckler MM. Amino acid substitutions at tryptophan 388 and tryptophan 412 of the HepG2 (GLUT1) glucose transporter inhibit transport activity and targeting to the plasma membrane in xenopus oocytes. J Biol Chem 1992; 267:7770-7776. Godfrey KM and Barker DJP. Fetal nutrition and adult disease. Am J Clin Nutr 2000; 71:1344–1352. Goodwin B, Redinbo MR, and Kliewer SA . Regulation of CYP3A gene transcription by the pregnane X receptor. Annu Rev Pharmacol Toxicol 2002; 42: 1–23. Handschin C and Meyer UA . Induction of drug metabolism: the role of nuclear receptors. Pharmacol Rev 2003; 55:649-673. Holmes LB, Harvey EA, Coull BA, Huntington KB, Khoshbin S, Hayes AM and Ryan LM. The teratogenicity of anticonvulsant drugs. N Engl J Med 2001; 344: 1132-1138. Huang W, Zhang J, Chua SS, Qatanani M, Han Y, Granata R and Moore DD. Induction of bilirubin clearance by the constitutive androstane receptor (CAR). Proc Natl Acad Sci USA 2003;100:4156–4161. Hosseinpour F, Moore R, Negishi M and Sueyoshi T. Ser-202 regulates the nuclear translocation of constitutive active/androstane receptor CAR. .Mol Pharmacol 2006; 69:1095-1102. Hayashi T, Hirshman MF, Fujii N, Habinowski SA, Witters LA and Goodyear LJ. Metabolic stress and altered glucose transport: activation of AMP-activated protein kinase as a unifying coupling mechanism. Diabetes 2000; 49:527–531. Hardie DG. The AMP-activated protein kinase pathway--new players upstream and downstream. J Cell Sci 2004; 117:5479-5487. Head JR, Fujikawa H and Casey ML. Preferential expression of glucose transporter-3 in the cotyledonary vessels of the placental vasculature. J Soc Gyn Invest 1999; 6:153A. Hume R, McGeechan A and Burchell A. Developmental disorders of glucose metabolism in infants. Child Care Health Dev 2002; 28 suppl 1:45–47. Hahn T, Barth S, Graf R, Engelmann M, Beslagic D, Reul JM, Holsboer F, Dohr G and Desoye G. Placental Glucose Transporter Expression Is Regulated by Glucocorticoids. J Clin Endocrinol Metab1999; 84:1445 - 1452. Hauguel-De MS, Challier J, Kacemi A, Cau¨ zac M, Malek A and Girard J. The GLUT3 glucose transporter isoform is differentially expressed within human placental cell types. J Clin Endocr Metab 1997; 82:2689–2694. Hussain K and Aynsley GA. The Effect of Prematurity and Intrauterine Growth Restriction on Glucose Metabolism in the Newborn. NeoReviews 2004; 5: e365-e369. Hayer ZM, Bruss M and Bonisch H. Expression and pharmacological profile of the human organic cation transporters hOCT1, hOCT2 and hOCT3. Br J Pharmacol 2002; 136:829-836. Hay WW, Jr Thureen PJ and Anderson SM. Intrauterine Growth Restriction. Neo Reviews 2001; 2:129. Horvath G, Sutto Z, Torbati A, Conner GE, Salathe M and Wanner A. Norepinephrine transport by the extraneuronal monoamine transporter in human bronchial arterial smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 2003; 285:L829-L837. Illsley NP. Glucose transporters in human placenta. Placenta 2000; 21:14-22. Illsley NP, Sellers MC and Wright RL. Glycemic regulation of glucose transporter expression and activity in the human placenta. Placenta 1998; 19: 517–524. Illsley NP, Hall S and Stacey TE. The modulation of glucose transfer across the human placenta by intervillous flow rates: an in vitro perfusion study. Trophoblast Res 1986; 2:539–548. John YL and Chiang. Bile acid regulation of gene expression: roles of nuclear hormone receptors. Endocr Rev 2002; 23:443. Jenkins JK and Boothby LA. Treatment of itching associated with intrahepatic cholestasis of pregnancy. Ann Pharmacother 2002;36:1462–1465. Joost HG and Thorens B. The extended GLUT-family of sugar/polyol transport facilitators: nomenclature, sequence characteristics, and potential function of its novel members (review).Mol Membr Biol 2001; 18:247-256. Jessen N and Goodyear LJ. Contraction signaling to glucose transport in skeletal muscle. J Appl Physiol 2005; 99:330–337. Jakobsen SN, Hardie DG, Morrice N and Tornqvist HE. 5’-AMPactivated protein kinase phosphorylates IRS-1 on Ser-789 in mouse C2C12 myotubes in response to 5-aminoimidazole-4-carboxamide riboside. J Biol Chem 2001; 276:46912–46916. Johnson LW and Smith CH. Glucose transport across the basal plasma membrane of human placental syncytiotrophoblast. Biochim Biophys Acta 1985; 815:44–50. Jansson T, Ylven K, Wennergren M, Powell TL. Glucose transport and system A activity in syncytiotrophoblast microvillous and basal plasma membranes in intrauterine growth restriction. Placenta 2002; 23:392-359. Jansson T, Cowley EA and Illsley NP. Cellular localization of glucose transporter messenger RNA in human placenta. Reprod Fertil Dev 1995; 7:1425–1430 Koyano S, Kurose K, Saito Y, Ozawa S, Hasegawa R, Komamura K, Ueno K, Kamakura S, Kitakaze M, Nakajima T, Matsumoto K, Akasawa A, Saito H and Sawada J. Functional characterization of four naturally occurring variants of human pregnane X receptor (PXR): one variant causes dramatic loss of both DNA binding activity and the transactivation of the CYP3A4 promoter/enhancer region. Drug Metab Dispos 2004; 32:149-154. Kliewer SA, Goodwin B and Willson TM. The nuclear pregnane X receptor: a key regulator of xenobiotic metabolism. Endocr Rev 2002; 23:687-702. Kast h R, Goodwin B, Tarr PT, Jones SA., Anisfeld AM, Stoltz CM, Tontonoz P, Kliewer S, Willson TM and Edwards PA. Regulation of multidrug resistanceassociated protein 2 (ABCC2) by the nuclear receptors pregnane X receptor, farnesoid X-activated receptor, and constitutive androstane receptor. J Biol Chem 2002;277:2908–2915. Kodama S, Koike C, Negishi M and Yamamoto Y. Nuclear receptors CAR and PXR cross talk with FOXO1 to regulate genes that encode drug-metabolizing and gluconeogenic enzymes. Mol Cell Biol 2004; 24:7931–7940. Kodama S and Negishi. Phenobarbital confers its diverse effects by activating the orphan nuclear receptor car. Drug Metab Rev 2006; 38:75-87. Kawamoto T, Sueyoshi T, Zelko I, Moore R, Washburn K and Negishi M. Phenobarbital-responsive nuclear translocation of the receptor CAR in induction of the CYP2B gene. Mol Cell Biol 1999; 19:6318–6322. Kahn BB, Alquier T, Carling D and Hardie DG. AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism, Cell Metab 2005; 1:15–25. Koh H, Hirshman MF, Fujii N, Arnolds DE, Rogers MJ, Mukai N, Jessen N, Ho RC and Goodyear LJ. Skeletal muscle knockout of LKB1 causes AICAR resistance but improves glucose tolerance. Diabetes 2005; 54 Suppl 1:384. Kudo Y, Boyd CA, Sargent IL and Redman CW. Hypoxia alters expression and function of syncytin and its receptor during trophoblast cell fusion of human placental BeWo cells: implications for impaired trophoblast syncytialisation in pre-eclampsia. Biochim Biophys Acta 2003, 1638, 63-71. Klepper J, Florcken A, Fischbarg J and Voit T. Effects of anticonvulsants on GLUT1-mediated glucose transport in GLUT1 deficiency syndrome in vitro. Eur J Pediatr 2003; 162:84-89. Lahtela JT, Arranto AJ and Sotaniemi EA. Enzyme inducers improve insulin sensitivity in non-insulin-dependent diabetic subjects. Diabetes 1985; 34: 911–916. Li J, Hu X, Selvakumar P, Russell RR III, Cushman SW, Holman GD and Young LH. Role of the nitric oxide pathway in AMPKmediated glucose uptake and GLUT4 translocation in heart muscle. Am J Physiol Endocrinol Metab 2004; 287:834–841. Lee X, Keith JC Jr, Stumm N, Moutsatsos I, McCoy JM, Crum CP, Genest D, Chin D, Ehrenfels C, Pijnenborg R, van Assche FA and Mi S. Downregulation of placental syncytin expression and abnormal protein localization in pre-eclampsia. Placenta 2001; 22:808-812. Makishima M, Okamoto AY, Repa JJ, Tu H, Learned RM, Luk A, Hull MV, Lustig KD, Mangelsdorf DJ and Shan B. Identification of a nuclear receptor for bile acids. Science 1999; 284:1362–1365. McKenna NJ, Lanz RB and O'Malley BW. Nuclear receptor coregulators: cellular and molecular biology. Endocr Rev 1999; 20:321-344. Mueckler M, Caruso C, Baldwin SA, Panico M, Blench I, Morris HR, Allard WJ, Lienhard GE and Lodish HF. Sequence and structure of human glucose transporter. Science 1985; 229:941- 945. Miinea CP, Sano H, Kane S, Sano E, Fukuda M, Peranen J, Lane WS, and Lienhard GE. AS160, the Akt substrate regulating GLUT4 translocation, has a functional Rab GTPase-activating protein domain. Biochem J 2005; 391:87–93. Maglich JM, Parks DJ, Moore LB, Collins JL, Goodwin B, Billin AN, Stoltz CA, Kliewer SA, Lambert MH, Willson MT, and Moore JT. Identification of a novel human constitutive androstane receptor (CAR) agonist and its use in the identification of CAR target genes. J Biol Chem 2003; 278:17277 - 17283. Murphy VE, Smith R, Giles WB, and Clifton VL. Endocrine regulation of human fetal growth: the Role of the mother, placenta, and fetus. Endocr Rev 2006; 27:141–169. Odegard RA, Vatten LJ and Nilsen ST. Preeclampsia and fetal growth. Obstet Gynecol 2000; 96:950–955. Puigserver P, Rhee J, Donovan J, Walkey CJ, Yoon JC, Oriente F, Kitamura Y, Altomonte J, Dong H, Accili D and Spiegelman BM. Insulin-regulated hepatic gluconeogenesis through FOXO1-PGC-1alpha interaction. Nature 2003; 423:550–555. Peraino C, Fry RJ and Staffeldt E. Reduction and enhancement by phenobarbital of hepatocarcinogenesis induced in the rat by 2-acetylaminofluorene, Cancer Res 1971; 31:1506–1512 Pattillo RA, and Gey GO. The establishment of a cell line of human hormone-synthesizing trophoblastic cells in vitro. Cancer Res 1968, 28:1231-1236. Quattrochi LC and Guzelian PS. Cyp3a regulation: from pharmacology to nuclear receptors. Drug Metab Dispos 2001; 29:615. Qatanani M, Zhang J and Moore DD. Role of the constitutive androstane receptor in xenobiotic-induced thyroid hormone metabolism. Endocrinology 2005, 146:995–1002. Rechavi RM, Carpentier AS, Duffraisse M and Laudet V How many nuclear hormone receptors in the human genome. Trends Genet 2001; 17:554 -556. Ramsden R, Beck N B, Sommer KM and Omiecinski C J. Phenobarbital responsiveness conferred by the 5'-flanking region of the rat CYP2B2 gene in transgenic mice. Gene 1999; 228:169–179. Rena G, Prescott A R, Guo S, Cohen P and Unterman TG. Roles of the forkhead in rhabdomyosarcoma (FKHR) phosphorylation sites in regulating 14-3-3 binding, transactivation and nuclear targeting. Biochem J 2001; 354:605–612. Rencurel F, Stenhouse A, Hawley,SA, Friedberg, T, Hardie DG, Sutherland C and Wolf CR. AMP-activated protein kinase mediates phenobarbital induction of CYP2B gene expression in hepatocytes and a newly derived human hepatoma cell line. J Biol Chem 2005; 280:4367–4373. Rencurel F, Foretz M, Kaufmann MR, Stroka D, Looser R, Leclerc I, Xavier GDS, Rutter GA, Viollet B and Meyer UA. Stimulation of AMP-Activated Protein Kinase is essential for the induction of drug metabolizing enzymes by phenobarbital in human and mouse Liver. Mol Pharmacol 2006; 70:1925 - 1934. Roaen S and Skaletsky H. Primer 3 on the WWW for general users and for biologist programmers. Methods Mol Biol 2000; 132:365-386. Russell RR, Bergeron R, Shulman GI and Young LH. Translocation of myocardial GLUT-4 and increased glucose uptake through activation of AMPK by AICAR. Am J Physiol Heart Circ Physiol 1999; 277:643. Staudinger JL, Goodwin B, Jones SA, Hawkins-Brown D, MacKenzie KI, LaTour A, Liu Y, Klaassen CD, Brown KK, Reinhard J, Willson TM, Koller BH and Kliewer SA. The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity. Proc Natl Acad Sci USA 2001; 98:3369-3374. Stedman CA, Liddle C, Coulter SA, Sonoda J, Alvarez JG, Moore DD, Evans RM and Downes M. Nuclear receptors constitutive androstane receptor and pregnane X receptor ameliorate cholestatic liver injury. Proc Natl Acad Sci USA 2005; 102:2063-2368. Swales K & Negishi M. CAR, driving into the future. Mol Endocrinol 2004;18:1589–1598. Seip M. Growth retardation, dysmorphic facies and minor malformations following massive exposure to phenobarbitone in utero. Acta Paediatr Scand 1976;65:617-621. Sugatani J, Yamakawa, K, Yoshinari K, Machida T, Takagi H, Mori M, Kakizaki S, Sueyoshi T, Negishi M and Miwa M. Identification of a defect in the UGT1A1 gene promoter and its association with hyperbilirubinemia. Biochem Biophys Res Commun 2002;292:492–497. Sakuma T, Honma R, Maguchi S, Tamaki H and Nemoto N. Different expression of hepatic and renal cytochrome P450s between the streptozotocin-induced diabetic mouse and rat. Xenobiotica 2001; 31:223–237. Sidhu JS and Omiecinski CJ. Insulin-mediated modulation of cytochrome P450 gene induction profiles in primary rat hepatocyte cultures. J Biochem Mol Toxicol 1999; 13:1–9. Saier MH, Beatty JT, Goffeau A, Harley KT, Heijne WH, uang SC, Jack DL, Jahn PS, Lew K, Liu J, Pao SS, aulsen IT, Tseng TT and Virk PS. The major ransporter facilitator superfamily. J Mol Microbiol Biotechnol 1999; 1:257- 279. Sato M and Mueckler M. A conserved amino acid motif (RXGRR) in the GLUT1 glucose transporter is an important determinant of membrane topology. J Biol Chem 1999; 274:24721-24725. SchuÈrmann A, Doege H, Ohnimus H, Monser V, Buchs A and Joost HG. Role of conserved arginine and glutamate residues on the cytosolic surface of glucose transporters (GLUT) for transporter function. Biochemistry 1997; 36:12897- 12902. Stapleton D, Mitchelhill KI, Gao G, Widmer J, Michell BJ, Teh T, House CM, Fernandez CS, Cox T, Witters LA and Kemp BE. Mammalian AMP-activated protein kinase subfamily. J Biol Chem 1996; 271:611–614. Stein SC, Woods A, Jones NA, Davison MD and Carling D. The regulation of AMP-activated protein kinase by phosphorylation. Biochem J 2000; 345: 437–443. Sakata M, Kurachi H, Imai T, Tadokoro C, Yamaguchi M, Yoshimoto Y, Oka Y and Miyake A. Increase in human placental glucose transporter-1 during pregnancy. Eur J Endocr 1995; 132:206–212. Sporstol M, Tapia G, .Malerod L, Mousavi SA and Berg.T. Pregnane X receptor-agonists down-regulate hepatic ATP-binding cassette transporter A1 and scavenger receptorclass B type I. BBRC 2005; 331:1533-1541 Stulc J. Extracellular transport pathways in the haemochorial placenta. Placenta 1998; 10:113-119. Shah SW, Zhao H, Low SY, Mcardle HJ and Hundal HS. Characterization of glucose transport and glucose transporters in the human choriocarcinoma cell line, BeWo. Placenta, 1999; 20: 651-659. Teasdale F and Jean-Jacques G. Intrauterine growth retardation: morphometry of the microvillous membrane of the human placenta. Placenta 1988; 9:47–55. Takagi H, Tanihara H, Seino Y and Yoshimura N. Characterization of glucose transporter in cultured human retinal pigment epithelial cells: gene expression and effect of growth factors. Invest Ophthalmol Vis Sc 1994; 35:170-177. Uldry M, Ibberson M, Riederer B, Chatton JY, Horisberger JD and Thorens B. Identification of a novel H+-myoinositol symporter expressed predominantly in the brain. EMBO J 2001; 20:4467–4477. Wilson JD and Foster DW. Williams Textbook of Endocrinology 1992; Saunders:Philadelphia. PA. ed 8. Wei P, Zhang J, Egan HM, Liang S and Moore DD. The nuclear receptor CAR mediates specific xenobiotic induction of drug metabolism. Nature 2000; 407:920–923. Wandel S, SchuÈrmann A, Becker W, Summers SA, Shanahan MF and Joost HG. Substitution of conserved tyrosine residues in helix 4 (Y143) and 7 (Y293) affects the activity, but not IAPS-forskolin binding, of the glucose transporter GLUT4. FEBS Lett 1994; 348:114-118. Wu X, George RL, Wang H, Conway SJ, Leibach FH and Ganapathy V. Structural and functional characteristics and tissue distribution pattern of rat OCTN1, an organic cation transporter, cloned from placenta. Biochim Biophys Acta 2000, 1446, 315-327. Xing AY, Challier JC, Leperq L, Cau¨zac M, Charron MJ, Girard J and Hauguel-de Mouzon S. Unexpected expression of glucose transporter 4 in villous stromal cells of human placenta. J Clin Endocr Metab 1998; 83:4097–4101. Xia X, Han J, and Zhang JZ. Stimulation of Glucose Transport by AMP-activated Protein Kinase via Activation of p38 Mitogen-activated Protein Kinase. J Biol Chem 2001; 276:41029 – 41034. Yamamoto Y, Kawamoto T and Negishi M. The role of the nuclear receptor CAR as a coordinate regulator of hepatic gene expression in defense against chemical toxicity. Arch Biochem Biophys 2003; 409:207–211. Yamamoto, Y, Moore R, Goldsworthy TL, Negishi M and Maronpot RR. The orphan nuclear receptor constitutive active/androstane receptor is essential for liver tumor promotion by phenobarbital in mice. Cancer Res 2004; 64: 7197–7200. Yoshinari K, Kobayashi K, Moore R, Kawamoto T and Negishi M. Identification of the nuclear receptor CAR:HSP90 complex in mouse liver and recruitment of protein phosphatase 2A in response to Phenobarbital. FEBS Lett 2003; 548: 17–20. Zhang J, Kuehl P, Green ED, Touchman JW, Watkins PB, Daly A, Hall SD, Maurel P, Relling M and Brimer C. The human pregnane X receptor: genomic structure and identification and functional characterization of natural allelic variants. Pharmacogenetics 2001; 11:555-572. Zhao A, Yu J, Lew JL, Huang L, Wright SD and Cui J. Polyunsaturated fatty acids are FXR ligands and differentially regulate expression of FXR targets DNA. Cell Biol 2004; 23:519 –526. Zelko I and Negishi M. Phenobarbital-elicited activation of nuclear receptor CAR in induction of cytochrome P450 genes. Biochem Biophys Res Commun 2000; 277:1–6. Zelko I, Sueyoshi T, Kawamoto T, Moore R and Negishi M. The peptide near the C terminus regulates receptor CAR nuclear translocation induced by xenochemicals in mouse liver. Mol Cell Biol 2001;21:2838–2846. Zhang J, Huang W, Qatanani M, Evans RM and Moore DD. The constitutive androstane receptor and pregnane X receptor function coordinately to prevent bile acid-induced hepatotoxicity. J Biol Chem 2004;279:49517–49522. Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J, Wu M, Ventre J, Doebber T, Fujii N, Musi N, Hirshman MF, Goodyear LJ and Moller DE. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Inves 2001; 108:1167–1174. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/28180 | - |
| dc.description.abstract | 葡萄糖轉運蛋白在分佈在身體的各種組織，負責將受質運送入細胞內產生ATP以供應活動所須的能量，主要表現在胎盤組織的葡萄糖轉運蛋白是葡萄糖轉運蛋白型一及型三，負責將母體中的葡萄糖運送至胎兒體內，以提供胎兒生長發育所需。GLUT1及GLUT3這兩種在膜上所發現的葡萄糖轉運蛋白具有類似的動力學特性，而且是鈉不依賴性的，而對D型的葡萄糖運送的選擇性大於L型。為了研究葡萄糖轉運蛋白的轉錄量是否會受到核內受體的調控，實驗中使用各種的核內受體的活化者來處理BeWo細胞株，BeWo細胞株是一種源於人類的絨毛膜癌細胞，可用在模擬胎盤的in vitro的模式中。
現階段實驗的結果中，首先要確定在BeWo細胞中有那些轉運蛋白的基因會被表現，以反轉錄-聚合酶連鎖反應可發現BeWo細胞中表現的轉運蛋白有運送肉鹼(carnitine)的OCTN2及葡萄糖轉運蛋白型一及型三。之後以各種核內受體的活化者來處理BeWo細胞，包括PXR的活化者rifampicin，FXR的活化者CDCA，及CAR的活化者phenobarbital。處理之後，以反轉錄-聚合酶連鎖反應結果發現以0.1 mM的phenobarbital處理後GLUT1及融合膜蛋白syncytin的mRNA轉錄量有下降的情形，而以rifampicin及CDCA處理後則無顯著的變化。為了進一步了解phenobarbital對GLUT1及GLUT3的影響，我們利用核內受體CAR的直接活化者CITCO及AMP-protein kinase的活化者AICAR，來探討BeWo細胞中的葡萄糖轉運蛋白型一及型三的調控模式，結果發現CITCO和濃度0.1 mM的phenobarbital對於GLUT1的轉錄量情況是相似的，因此推論在低濃度下的phenobarbital可能是透過CAR來調控GLUT1；而GLUT3則沒明顯變化。然而在濃度為0.5 mM及1 mM的情況下，GLUT1的轉錄量反而會增加，而此情況和AICAR處理之後GLUT1及GLUT3的轉錄表現情況相似，因此可知道在高濃度的phenobarbital會活化AMPK進而調節GLUT1的表現。除此之外，在以氚標示的2去氧D葡萄糖來觀察BeWo細胞對葡萄糖的攝取量時其動力學參數為Km= 0.55±0.01mM，Vm= 28.37±1.93nmol/10min.mg /protein，並有一個不飽和參數κ=1.46±0.08mL/10min.mg /protein，在加入0.5 mM及1 mM濃度的phenobarbital之後24小時，得到Km值均有增加，不飽和常數k值減小，但是其Vmax則變化不大(Km= 1.04±0.03 mM，Vm= 30.35±1.57 nmol/10min.mg /protein，κ=0.89±0.04mL/ 10 min.mg /protein)，而以1 mM濃度的phenobarbital處理24小時之後，其動力學參數Km為1.05±0.22 mM；Vm為34.52±4.49 nmol/10min.mg/protein；不飽合常數k為1.38±0.13 mL/10min.mg /protein。以1 mM濃度的phenobarbital處理72小時之後，其動力學參數Km為1.08±0.23 mM；Vm為24.49±4.16 nmol/10min.mg/protein；不飽合常數k為0.83±0.07 mL/10min.mg /protein。因此可以推論在加入較高濃度的phenobarbital經過24小時及72小時處理之後，會降低葡萄糖轉運蛋白對葡萄糖的親和能力，若是以0.5 mM或是1 mM的phenobarbital處理24小時後，其在生理狀態下的葡糖糖濃度對葡萄糖轉運蛋白的運送能力則影響不大，然而在1 mM的phenobarbital處理72小時之後會降低葡萄糖轉運蛋白的運送能力。 | zh_TW |
| dc.description.abstract | The sodium-independent facilitated glucose transporters, GLUT1 and GLUT3, are expressed in placental tissues and are responsible for glucose transfer from maternal to the fetus. Deficiency in glucose levels may cause detrimental effects on fetal growth and development. It was reported that phenobarbital can be related to occurrence of intrauterine growth retardation (IUGR). Although phenobarbital is known to be an indirect activator of CAR, an orphan nuclear receptor, the interaction between phenobarbital and placental glucose transporters is far from clear. To investigate the impacts of phenobarbital on the expression and functions of placental GLUT1 and GLUT3, compounds including Phenobarbital (an indirect CAR activator), CITCO (a direct CAR activator) and AICAR (an AMPK activator) were used to treat BeWo cells, a cell line derived from human choriocarcinoma and has therefore been used as an in vitro placenta model.
In the RT-PCR study, the results showed that, at a concentration of 0.1 mM, phenobarbital down-regulated m-RNA levels of both syncytin and GLUT1, but not GLUT3. However, at concentrations of 0.5 mM and 1 mM, phenobarbital increased m-RNA levels of GLUT1 but decreased that of GLUT3. The treatment of CITCO caused similar effects comparable to that of phenobarbital at a concentration of 0.1 mM. On the other hand, AICAR showed similar effects comparable to that of phenobarbital at concentrations of 0.5 mM and 1 mM. In the cellular uptake study, the results showed that the Km and Vm values of 3H-2-deoxy-D-glucose in un-treated BeWo cells are 0.55±0.01 mM and 28.37±1.93 nmol/10min-mg/ protein, respectively. There is also with a non-saturable constant k=1.46±0.08mL/10min.mg /protein .After the treatment (24 hours) of 0.5 mM phenobarbital, the Km and Vm values of 3H-2-deoxy-D-glucose are 1.04±0.03 mM and 30.35±1.57 nmol/10min-mg/ protein, respectively. Non-saturable constant k is 0.89±0.04mL/ 10 min.mg /protein. After the treatment (24 hours and 72 hours) of 1 mM phenobarbital, the Km and Vm values of 3H-2-deoxy-D-glucose are 1.05±0.22mM and 34.52±4.49 nmol/10min-mg/ protein (24 hours), 1.08±0.23 mM and 24.49±4.16 nmol/10min.mg/protein (72 hours) respectively. Non-saturable constant k is 1.38±0.13 mL/ 10 min.mg /protein(24 hours) and 0.83±0.07 mL/10min.mg /protein(72 hours). In conclusion, the impacts of phenobarbital on GLUT1 and GLUT3 are concentration-dependent, in which phenobarbital activates CAR at low concentration and AMPK at high concentration, respectively. Given that plasma levels of phenobarbital are about 0.1 mM, this study indicate that phenobarbital may decrease placental glucose transfer by activating CAR. After the treatment of 0.5 mM and 1 mM phenobarbital, Vmax is unchanged but the value of Km increase 24 hours later.After 1 mM phenobarbital treatment, Vmax is decreased than control. These results suggest that the affinity of glucose transporters decrease after phenobarbital treatment. In higher concentration of phenobarbital treatment, the transport ability of glucose transporters is no significantly changed under physiological condition after 24 hours. However, higher concentration of phenobarbital (1 mM) treat 72 hours, the transport ability of glucose transporters is somehow decreased. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T00:02:15Z (GMT). No. of bitstreams: 1 ntu-96-R94423016-1.pdf: 1823493 bytes, checksum: 38a384bd069172017c61e0948cebeb4c (MD5) Previous issue date: 2007 | en |
| dc.description.tableofcontents | 誌謝…………………………………………………………………………………II
中文摘要……………………………………………………………………………III 英文摘要……………………………………………………………………………V 第一章 緒論………………………………………………………………………..1 一 細胞核受體(Nuclear Receptors)(NRs)…………………………………1 二 Pregnane X Receptor(PXR)……………………………………………..2 三 Farnesoid X Receptor(FXR)…………………………………………….4 四Constitutive Androstane Receptor(CAR)………………………………..4 五CAR與Phenobarbital的關係…………………………………………..5 六 Phenobarbital 對CAR活化的作用機制………………………………8 七 葡萄糖轉運蛋白(glucose transporter)………………………………......9 八 人類胎盤中的葡萄糖轉運蛋白(Placental glucose transporters)……...11 第二章 實驗目的…………………………………………………………………..33 第三章 實驗材料…………………………………………………………………..34 一 BeWo細胞株的培養及藥物的處理…………………………………….34 二BeWo細胞株RNA的粹取………………………………………………35 三 BeWo的Total RNA的反轉錄反應…………………………………….35 四 聚合酶連鎖反應…………………………………………………………36 五 半定量聚合酶連鎖反應…………………………………………………38 六 內因性控制的選擇………………………...…………………………….38 七 蛋白質濃度的測定……………………………………………………….39 八 葡萄糖在BeWo細胞中攝取的研究…………………………………….39 九 其它……………………………………………………………………….40 第四章 實驗方法…………………………………………………………………...42 一 BeWo細胞株的培養(Cell culture of BeWo cell line)……………………...42 二 BeWo細胞株RNA的粹取(Total RNA extraction of BeWo cell line)…….42 三BeWo的Total RNA的反轉錄反應(Reverse Transcription of BeWo total RNA)………………………………………………………….43 四 聚合酶連鎖反應…………………………………………………………….43 五 半定量聚合酶連鎖反應(Semi-quantitative PCR)…………………………..44 六 內因性控制的選擇(Internal control choice)………………………………..44 七 以藥物處理BeWo細胞株(Drug treatment of BeWo cell line)…………….45 八 藥物處理後BeWo細胞株中融合膜蛋白(Syncytin)及葡萄糖轉運膜蛋 白型一(GLUT1) mRNA的變化量之測定………………………………….45 九 以藥物處理BeWo細胞株(Drug treatment of BeWo cell line)……………..46 十 藥物處理後BeWo細胞株中葡萄糖轉運子膜蛋白型一(GLUT1) 及型三(GLUT3) mRNA的變化量之測定…………………………………47 十一 蛋白質濃度的測定(Bio-Rad DC protein assay)………………………….47 十二 葡萄糖在BeWo細胞攝取之研究………………………………………..48 十三 數據分析…………………………………………………………………..48 第五章 實驗結果……………………………………………………………………50 第六章 結果討論……………………………………………………………………54 第七章 結論…………………………………………………………………………60 第八章 參考文獻…………………………………………………………………....87 原始數據及附錄……………………………………………………………………..97 圖目錄 圖一 A核內受體的結構圖 B核內受體的DNA結合區C相關的核 內受體種系發生圖………………………………………………………..15 圖二 各種能夠活化人類FXR的膽酸結構……………………………………..16 圖三 肝藏中膽酸的生合成路徑此圖顯示兩個主要路徑圖…………………....17 圖四 CAR跟FoxO1的交互作用圖......................................................................18 圖五 PB對核內受體CAR的作用圖…………………………………………….19 圖六 葡萄糖轉運蛋白(glucose transporter)家族分類圖.......................................20 圖七 葡萄糖轉運蛋白class I的結構圖………………………………………….21 圖八 AMPK在細胞中的生理角色示意圖………………………………………22 圖九 AMPK在細胞中活化或抑制的蛋白質圖…………………………………23 圖十 AICAR透過AMPK對葡萄糖轉運蛋白的調節作用圖………….………24 圖十一AMPK對葡萄糖轉運蛋白的調節作用圖………………………………… 25 圖十二 母親的胎盤與胎兒之間關係示意圖………………………………… 26 圖十三 分佈在胎盤中的葡萄糖轉運蛋白…………………………………………27 圖十四 BeWo cell line transporters的種類…………………………………………61 圖十五 BeWo cell line transporters的種類…………………………………………61 圖十六 Syncytin mRNA表現的半定量PCR表現及定量圖………………………62 圖十七 GLUT-1 mRNA表現的半定量PCR表現及定量圖………………………63 圖十八 GLUT-3 mRNA表現的半定量PCR表現及定量圖………………………63 圖十九 hGAPDH mRNA表現的半定量PCR表現及定量圖……………………..64 圖二十 內因性控制組(hGAPDH、18 sRNA、beta-actin)mRNA的PCR表現及定量圖………………………………………………………65 圖二十一 以藥物處理之後syncytin mRNA的PCR表現及定量圖…………………………………67 圖二十二 以藥物處理之後GLUT1 mRNA的PCR表現及定量圖………………68 圖二十三 GLUT1 mRNA在不同的時間點下以CITCO處理之後的PCR及表現量圖……………………………………………………..69 圖二十四 GLUT1 mRNA在不同的時間點下以phenobarbital處理之後的PCR及表現量圖………………………………………………...70 圖二十五 GLUT1 mRNA在不同的時間點下以AICAR處理之後的PCR及表現量圖…………………………………………………………71 圖二十六 hGAPDH以各種藥物處理後在基因擴增反應中以22 cycles 反應後的PCR圖…………………………………………………………72 圖二十七 GLUT3以22 cycles的hGAPDH當internal control在CITCO處理下的mRNA之PCR及表現量圖………………………………….72 圖二十八 GLUT3以22 cycles的hGAPDH當internal control在phenobarbital處理下的mRNA之PCR及表現量圖…………………..73 圖二十九 GLUT3以22 cycles的hGAPDH當internal controla以AICAR處理後的mRNA之PCR及表現量圖………………………...74 圖三十 GLUT1以25 cycles的hGAPDH當internal control以0.5 pmMhenobarbital處理後的mRNA之PCR及表現量圖…………………...75 圖三十一 GLUT1以25 cycles的hGAPDH當internal control以1 mM phenobarbital處理後的mRNA之PCR及表現量圖…………………...76 圖三十二 GLUT3以25 cycles的hGAPDH當internal control以0.5 mM phenobarbital處理後的mRNA之PCR及表現量圖…………………...77 圖三十三 GLUT3以25 cycles的hGAPDH當internal control以1 mM phenobarbital處理後的mRNA之PCR及表現量圖……………………78 圖三十四 2去氧D葡萄糖濃度和2去氧D葡萄糖攝取量在BeWo細胞中的關係圖……………………………………………………………79 圖三十五 2去氧D葡萄糖濃度和2去氧D葡萄糖攝取量在0.5 mM的phenobarbital處理24小時後在BeWo細胞中的關係………………….80 圖三十六 2去氧D葡萄糖濃度和2去氧D葡萄糖攝取量在1 mM的phenobarbital處理24小時後和控制組之比較圖……………………81 圖三十七2去氧D葡萄糖濃度和2去氧D葡萄糖攝取量在1 mM的phenobarbital處理72小時後和控制組之比較圖……………………82 圖三十八2去氧D葡萄糖濃度和2去氧D葡萄糖攝取量在0.5 mM的 phenobarbital處理24小時後和控制組之Michaelis-Menten比較圖….83 圖三十九 2去氧D葡萄糖濃度和2去氧D葡萄糖攝取量在1 mM的phenobarbital處理24小時後和控制組之Michaelis-Menten比較圖…84 圖四十 2去氧D葡萄糖濃度和2去氧D葡萄糖攝取量在1 mM的phenobarbital處理72小時後和控制組之Michaelis-Menten比較圖………………...85 表目錄 表一 在各種細胞株及物種中可活化PXR的化合物表列……………………28 表二 核內受體活化Cytochrome P 450示意圖……………………………….29 表三 葡萄糖轉運子家族……………………………………………………….30 表四 引發胎兒IUGR及早產的因素………………………………………….31 表五 以實驗動物模式引發IUGR的相關研究及文獻……………………….32 表六 BeWo細胞在有無phenobarbital處理後的動力學參數對照表……......86 | |
| dc.language.iso | zh-TW | |
| dc.subject | 子宮內胎兒生長遲緩 | zh_TW |
| dc.subject | 胎盤 | zh_TW |
| dc.subject | 葡萄糖轉運蛋白 | zh_TW |
| dc.subject | glucose transporter | en |
| dc.subject | phenobarbital | en |
| dc.subject | intrauterine growth retadation(IUGR) | en |
| dc.subject | GLUT3 | en |
| dc.subject | GLUT1 | en |
| dc.subject | placenta | en |
| dc.title | Phenobarbital 對胎盤葡萄糖轉運蛋白GLUT1及GLUT3影響之研究 | zh_TW |
| dc.title | Effects of phenobarbital on human placental glucose transporters type I and type III | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 95-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 孔繁璐(Fan-Lu Kung),顧記華(Jih-Hwa Guh) | |
| dc.subject.keyword | 胎盤,葡萄糖轉運蛋白,子宮內胎兒生長遲緩, | zh_TW |
| dc.subject.keyword | placenta,glucose transporter,GLUT1,GLUT3,intrauterine growth retadation(IUGR),phenobarbital, | en |
| dc.relation.page | 107 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2007-07-31 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 藥學研究所 | zh_TW |
| 顯示於系所單位： | 藥學系 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-96-1.pdf 未授權公開取用 | 1.78 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。