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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 邱智賢(Chih-Hsien Chiu) | |
| dc.contributor.author | Li-Ying Hung | en |
| dc.contributor.author | 洪立盈 | zh_TW |
| dc.date.accessioned | 2021-06-16T10:37:27Z | - |
| dc.date.available | 2013-08-20 | |
| dc.date.copyright | 2013-08-20 | |
| dc.date.issued | 2013 | |
| dc.date.submitted | 2013-08-13 | |
| dc.identifier.citation | Abumrad, N.A., el-Maghrabi, M.R., Amri, E.Z., Lopez, E., Grimaldi, P.A., 1993. Cloning of a rat adipocyte membrane protein implicated in binding or transport of long-chain fatty acids that is induced during preadipocyte differentiation. Homology with human CD36. The Journal of biological chemistry 268, 17665-17668.
Adeli, K., Taghibiglou, C., Van Iderstine, S.C., Lewis, G.F., 2001. Mechanisms of hepatic very low-density lipoprotein overproduction in insulin resistance. Trends in cardiovascular medicine 11, 170-176. Aires, C.C., Ijlst, L., Stet, F., Prip-Buus, C., de Almeida, I.T., Duran, M., Wanders, R.J., Silva, M.F., 2010. Inhibition of hepatic carnitine palmitoyl-transferase I (CPT IA) by valproyl-CoA as a possible mechanism of valproate-induced steatosis. Biochemical pharmacology 79, 792-799. Amacher, D.E., 2011. Strategies for the early detection of drug-induced hepatic steatosis in preclinical drug safety evaluation studies. Toxicology 279, 10-18. Amini-Shirazi, N., Ghahremani, M.H., Ahmadkhaniha, R., Mandegary, A., Dadgar, A., Abdollahi, M., Shadnia, S., Pakdaman, H., Kebriaeezadeh, A., 2010. Influence of CYP2C9 polymorphism on metabolism of valproate and its hepatotoxin metabolite in Iranian patients. Toxicology mechanisms and methods 20, 452-457. Araya, J., Rodrigo, R., Videla, L.A., Thielemann, L., Orellana, M., Pettinelli, P., Poniachik, J., 2004. Increase in long-chain polyunsaturated fatty acid n - 6/n - 3 ratio in relation to hepatic steatosis in patients with non-alcoholic fatty liver disease. Clinical science 106, 635-643. Argo, C.K., Caldwell, S.H., 2009. Epidemiology and natural history of non-alcoholic steatohepatitis. Clinics in liver disease 13, 511-531. Barrero, M.J., Camarero, N., Marrero, P.F., Haro, D., 2003. Control of human carnitine palmitoyltransferase II gene transcription by peroxisome proliferator-activated receptor through a partially conserved peroxisome proliferator-responsive element. The biochemical journal 369, 721-729. Berardi, M.J., Shih, W.M., Harrison, S.C., Chou, J.J., 2011. Mitochondrial uncoupling protein 2 structure determined by NMR molecular fragment searching. Nature 476, 109-113. Bianchi, A., Evans, J.L., Iverson, A.J., Nordlund, A.C., Watts, T.D., Witters, L.A., 1990. Identification of an isozymic form of acetyl-CoA carboxylase. The Journal of biological chemistry 265, 1502-1509. Blouin, A., Bolender, R.P., Weibel, E.R., 1977. Distribution of organelles and membranes between hepatocytes and nonhepatocytes in the rat liver parenchyma. A stereological study. The Journal of cell biology 72, 441-455. Bonen, A., Luiken, J.J., Arumugam, Y., Glatz, J.F., Tandon, N.N., 2000. Acute regulation of fatty acid uptake involves the cellular redistribution of fatty acid translocase. The Journal of biological chemistry 275, 14501-14508. Bradbury, M.W., 2006. Lipid metabolism and liver inflammation. I. Hepatic fatty acid uptake: possible role in steatosis. American journal of physiology. Gastrointestinal and liver physiology 290, G194-198. Braissant, O., Foufelle, F., Scotto, C., Dauca, M., Wahli, W., 1996. Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat. Endocrinology 137, 354-366. Breslow, J.L., Sloan, H.R., Ferrans, V.J., Anderson, J.L., Levy, R.I., 1973. Characterization of the mouse liver cell line FL83B. Experimental cell research 78, 441-453. Brown, M.S., Goldstein, J.L., 1976. Receptor-mediated control of cholesterol metabolism. Science 191, 150-154. Browning, J.D., Szczepaniak, L.S., Dobbins, R., Nuremberg, P., Horton, J.D., Cohen, J.C., Grundy, S.M., Hobbs, H.H., 2004. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 40, 1387-1395. Campbell, S.E., Tandon, N.N., Woldegiorgis, G., Luiken, J.J., Glatz, J.F., Bonen, A., 2004. A novel function for fatty acid translocase (FAT)/CD36: involvement in long chain fatty acid transfer into the mitochondria. The Journal of biological chemistry 279, 36235-36241. Carmichael, J., DeGraff, W.G., Gazdar, A.F., Minna, J.D., Mitchell, J.B., 1987. Evaluation of a tetrazolium-based semiautomated colorimetric assay: assessment of chemosensitivity testing. Cancer research 47, 936-942. Cases, S., Novak, S., Zheng, Y.W., Myers, H.M., Lear, S.R., Sande, E., Welch, C.B., Lusis, A.J., Spencer, T.A., Krause, B.R., Erickson, S.K., Farese, R.V., Jr., 1998a. ACAT-2, a second mammalian acyl-CoA:cholesterol acyltransferase. Its cloning, expression, and characterization. The Journal of biological chemistry 273, 26755-26764. Cases, S., Smith, S.J., Zheng, Y.W., Myers, H.M., Lear, S.R., Sande, E., Novak, S., Collins, C., Welch, C.B., Lusis, A.J., Erickson, S.K., Farese, R.V., Jr., 1998b. Identification of a gene encoding an acyl CoA:diacylglycerol acyltransferase, a key enzyme in triacylglycerol synthesis. Proceedings of the National Academy of Sciences of the United States of America 95, 13018-13023. Cases, S., Stone, S.J., Zhou, P., Yen, E., Tow, B., Lardizabal, K.D., Voelker, T., Farese, R.V., Jr., 2001. Cloning of DGAT2, a second mammalian diacylglycerol acyltransferase, and related family members. The Journal of biological chemistry 276, 38870-38876. Chalasani, N., Bjornsson, E., 2010. Risk factors for idiosyncratic drug-induced liver injury. Gastroenterology 138, 2246-2259. Chang, T.K.H., Abbott, F.S., 2006. Oxidative stress as a mechanism of valproic acid-associated hepatotoxicity. Drug metabolism reviews 38, 627-639. Chateauvieux, S., Morceau, F., Dicato, M., Diederich, M., 2010. Molecular and therapeutic potential and toxicity of valproic acid. Journal of biomedicine & biotechnology 2010, Article ID 479364, 1-18. Chen, G., Liang, G., Ou, J., Goldstein, J.L., Brown, M.S., 2004. Central role for liver X receptor in insulin-mediated activation of Srebp-1c transcription and stimulation of fatty acid synthesis in liver. Proceedings of the National Academy of Sciences of the United States of America 101, 11245-11250. Clarke, S.D., 1993. Regulation of fatty acid synthase gene expression: an approach for reducing fat accumulation. Journal of animal science 71, 1957-1965. Clement, B., Grimaud, J.A., Campion, J.P., Deugnier, Y., Guillouzo, A., 1986. Cell types involved in collagen and fibronectin production in normal and fibrotic human liver. Hepatology 6, 225-234. Cohen, J.C., Horton, J.D., Hobbs, H.H., 2011. Human fatty liver disease: old questions and new insights. Science 332, 1519-1523. Coleman, R.A., Reed, B.C., Mackall, J.C., Student, A.K., Lane, M.D., Bell, R.M., 1978. Selective changes in microsomal enzymes of triacylglycerol phosphatidylcholine, and phosphatidylethanolamine biosynthesis during differentiation of 3T3-L1 preadipocytes. The Journal of biological chemistry 253, 7256-7261. Cooper, A.D., 1997. Hepatic uptake of chylomicron remnants. Journal of lipid research 38, 2173-2192. Daly, A.K., Day, C.P., 2009. Genetic association studies in drug-induced liver injury. Seminars in liver disease 29, 400-411. Dam-Larsen, S., Becker, U., Franzmann, M.B., Larsen, K., Christoffersen, P., Bendtsen, F., 2009. Final results of a long-term, clinical follow-up in fatty liver patients. Scandinavian journal of gastroenterology 44, 1236-1243. Davern, T.J., 2012. Drug-induced liver disease. Clinics in liver disease 16, 231-245. Davis, C.G., Goldstein, J.L., Sudhof, T.C., Anderson, R.G., Russell, D.W., Brown, M.S., 1987. Acid-dependent ligand dissociation and recycling of LDL receptor mediated by growth factor homology region. Nature 326, 760-765. Day, C.P., James, O.F., 1998. Steatohepatitis: a tale of two 'hits'? Gastroenterology 114, 842-845. Delisle, G., Fritz, I.B., 1967. Interrelations between hepatic fatty acid oxidation and gluconeogenesis: a possible regulatory role of carnitine palmityltransferase. Proceedings of the National Academy of Sciences of the United States of America 58, 790-797. Denizot, F., Lang, R., 1986. Rapid colorimetric assay for cell growth and survival. Modifications to the tetrazolium dye procedure giving improved sensitivity and reliability. Journal of immunological methods 89, 271-277. Diraison, F., Moulin, P., Beylot, M., 2003. Contribution of hepatic de novo lipogenesis and reesterification of plasma non esterified fatty acids to plasma triglyceride synthesis during non-alcoholic fatty liver disease. Diabetes & metabolism 29, 478-485. Donnelly, K.L., Smith, C.I., Schwarzenberg, S.J., Jessurun, J., Boldt, M.D., Parks, E.J., 2005. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. The Journal of clinical investigation 115, 1343-1351. Eguchi, Y., Hyogo, H., Ono, M., Mizuta, T., Ono, N., Fujimoto, K., Chayama, K., Saibara, T., Jsg, N., 2012. Prevalence and associated metabolic factors of nonalcoholic fatty liver disease in the general population from 2009 to 2010 in Japan: a multicenter large retrospective study. Journal of gastroenterology 47, 586-595. Ehehalt, R., Fullekrug, J., Pohl, J., Ring, A., Herrmann, T., Stremmel, W., 2006. Translocation of long chain fatty acids across the plasma membrane--lipid rafts and fatty acid transport proteins. Molecular and cellular biochemistry 284, 135-140. El-Khoury, T.G., Bahr, G.M., Echtay, K.S., 2011. Muramyl-dipeptide-induced mitochondrial proton leak in macrophages is associated with upregulation of uncoupling protein 2 and the production of reactive oxygen and reactive nitrogen species. The FEBS journal 278, 3054-3064. El Khadir-Mounier, C., Le Fur, N., Powell, R.S., Diot, C., Langlois, P., Mallard, J., Douaire, M., 1996. Cloning and characterization of the 5' end and promoter region of the chicken acetyl-CoA carboxylase gene. The biochemical journal 314 ( Pt 2), 613-619. Elphick, L.M., Pawolleck, N., Guschina, I.A., Chaieb, L., Eikel, D., Nau, H., Harwood, J.L., Plant, N.J., Williams, R.S., 2012. Conserved valproic-acid-induced lipid droplet formation in Dictyostelium and human hepatocytes identifies structurally active compounds. Disease models & mechanisms 5, 231-240. Endemann, G., Stanton, L.W., Madden, K.S., Bryant, C.M., White, R.T., Protter, A.A., 1993. CD36 is a receptor for oxidized low density lipoprotein. The Journal of biological chemistry 268, 11811-11816. Enoch, H.G., Catala, A., Strittmatter, P., 1976. Mechanism of rat liver microsomal stearyl-CoA desaturase. Studies of the substrate specificity, enzyme-substrate interactions, and the function of lipid. The Journal of biological chemistry 251, 5095-5103. Evans, H., De Tomaso, T., Quail, M., Rogers, J., Gracey, A.Y., Cossins, A.R., Berenbrink, M., 2008. Ancient and modern duplication events and the evolution of stearoyl-CoA desaturases in teleost fishes. Physiological genomics 35, 18-29. Febbraio, M., Abumrad, N.A., Hajjar, D.P., Sharma, K., Cheng, W., Pearce, S.F., Silverstein, R.L., 1999. A null mutation in murine CD36 reveals an important role in fatty acid and lipoprotein metabolism. The Journal of biological chemistry 274, 19055-19062. Feige, J.N., Gelman, L., Michalik, L., Desvergne, B., Wahli, W., 2006. From molecular action to physiological outputs: peroxisome proliferator-activated receptors are nuclear receptors at the crossroads of key cellular functions. Progress in lipid research 45, 120-159. Fritz, I.B., Schultz, S.K., Srere, P.A., 1963. Properties of partially purified carnitine acetyltransferase. The Journal of biological chemistry 238, 2509-2517. Fujimura, H., Murakami, N., Kurabe, M., Toriumi, W., 2009. In vitro assay for drug-induced hepatosteatosis using rat primary hepatocytes, a fluorescent lipid analog and gene expression analysis. Journal of applied toxicology : JAT 29, 356-363. Ganesh Bhat, B., Wang, P., Kim, J.H., Black, T.M., Lewin, T.M., Fiedorek, F.T., Jr., Coleman, R.A., 1999. Rat sn-glycerol-3-phosphate acyltransferase: molecular cloning and characterization of the cDNA and expressed protein. Biochimica et biophysica acta 1439, 415-423. Gerstner, T., Bell, N., Konig, S., 2008. Oral valproic acid for epilepsy--long-term experience in therapy and side effects. Expert opinion on pharmacotherapy 9, 285-292. Gomez-Lechon, M.J., Donato, M.T., Martinez-Romero, A., Jimenez, N., Castell, J.V., O'Connor, J.E., 2007. A human hepatocellular in vitro model to investigate steatosis. Chemico-biological interactions 165, 106-116. Gottlicher, M., Minucci, S., Zhu, P., Kramer, O.H., Schimpf, A., Giavara, S., Sleeman, J.P., Lo Coco, F., Nervi, C., Pelicci, P.G., Heinzel, T., 2001. Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells. The EMBO journal 20, 6969-6978. Greco, D., Kotronen, A., Westerbacka, J., Puig, O., Arkkila, P., Kiviluoto, T., Laitinen, S., Kolak, M., Fisher, R.M., Hamsten, A., Auvinen, P., Yki-Jarvinen, H., 2008. Gene expression in human NAFLD. American journal of physiology. Gastrointestinal and liver physiology 294, G1281-1287. Greenspan, P., Mayer, E.P., Fowler, S.D., 1985. Nile red: a selective fluorescent stain for intracellular lipid droplets. The Journal of cell biology 100, 965-973. Hajri, T., Abumrad, N.A., 2002. Fatty acid transport across membranes: relevance to nutrition and metabolic pathology. Annual review of nutrition 22, 383-415. Hammond, L.E., Gallagher, P.A., Wang, S., Hiller, S., Kluckman, K.D., Posey-Marcos, E.L., Maeda, N., Coleman, R.A., 2002. Mitochondrial glycerol-3-phosphate acyltransferase-deficient mice have reduced weight and liver triacylglycerol content and altered glycerolipid fatty acid composition. Molecular and cellular biology 22, 8204-8214. Han, D., Dara, L., Win, S., Than, T.A., Yuan, L., Abbasi, S.Q., Liu, Z.X., Kaplowitz, N., 2013. Regulation of drug-induced liver injury by signal transduction pathways: critical role of mitochondria. Trends in pharmacological sciences 34, 243-253. Hashimoto, T., Cook, W.S., Qi, C., Yeldandi, A.V., Reddy, J.K., Rao, M.S., 2000. Defect in peroxisome proliferator-activated receptor alpha-inducible fatty acid oxidation determines the severity of hepatic steatosis in response to fasting. The Journal of biological chemistry 275, 28918-28928. Hawkins, M.T., Lewis, J.H., 2012. Latest advances in predicting DILI in human subjects: focus on biomarkers. Expert opinion on drug metabolism & toxicology 8, 1521-1530. Holt, M.P., Ju, C., 2006. Mechanisms of drug-induced liver injury. The AAPS journal 8, E48-54. Hoofnagle, J.H., 2004. Drug-induced liver injury network (DILIN). Hepatology 40, 773. Horton, J.D., Shimomura, I., Brown, M.S., Hammer, R.E., Goldstein, J.L., Shimano, H., 1998. Activation of cholesterol synthesis in preference to fatty acid synthesis in liver and adipose tissue of transgenic mice overproducing sterol regulatory element-binding protein-2. Journal of clinical investigation 101, 2331-2339. Hua, X., Wu, J., Goldstein, J.L., Brown, M.S., Hobbs, H.H., 1995. Structure of the human gene encoding sterol regulatory element binding protein-1 (SREBF1) and localization of SREBF1 and SREBF2 to chromosomes 17p11.2 and 22q13. Genomics 25, 667-673. Hua, X., Yokoyama, C., Wu, J., Briggs, M.R., Brown, M.S., Goldstein, J.L., Wang, X., 1993. SREBP-2, a second basic-helix-loop-helix-leucine zipper protein that stimulates transcription by binding to a sterol regulatory element. Proceedings of the National Academy of Sciences of the United States of America 90, 11603-11607. Hussein, R., El-Halabi, M., Ghaith, O., Jurdi, N., Azar, C., Mansour, N., Sharara, A.I., 2011. Severe hepatotoxicity associated with the combination of spiramycin plus metronidazole. Arab journal of gastroenterology : the official publication of the Pan-Arab Association of Gastroenterology 12, 44-47. Ibrahimi, A., Abumrad, N.A., 2002. Role of CD36 in membrane transport of long-chain fatty acids. Current opinion in clinical nutrition and metabolic care 5, 139-145. Inoue, M., Ohtake, T., Motomura, W., Takahashi, N., Hosoki, Y., Miyoshi, S., Suzuki, Y., Saito, H., Kohgo, Y., Okumura, T., 2005. Increased expression of PPARgamma in high fat diet-induced liver steatosis in mice. Biochemical and biophysical research communications 336, 215-222. Ishibashi, S., Brown, M.S., Goldstein, J.L., Gerard, R.D., Hammer, R.E., Herz, J., 1993. Hypercholesterolemia in low density lipoprotein receptor knockout mice and its reversal by adenovirus-mediated gene delivery. The Journal of clinical investigation 92, 883-893. Issemann, I., Green, S., 1990. Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature 347, 645-650. Jayakumar, A., Chirala, S.S., Wakil, S.J., 1997. Human fatty acid synthase: assembling recombinant halves of the fatty acid synthase subunit protein reconstitutes enzyme activity. Proceedings of the National Academy of Sciences of the United States of America 94, 12326-12330. Ji, Q., Shi, X., Lin, R., Mao, Y., Zhai, X., Lin, Q., Zhang, J., 2010. Participation of lipid transport and fatty acid metabolism in valproate sodium-induced hepatotoxicity in HepG2 cells. Toxicology in vitro : an international journal published in association with BIBRA 24, 1086-1091. Johannessen, C.U., Johannessen, S.I., 2003. Valproate: Past, present, and future. CNS drug reviews 9, 199-216. Kaestner, K.H., Ntambi, J.M., Kelly, T.J., Jr., Lane, M.D., 1989. Differentiation-induced gene expression in 3T3-L1 preadipocytes. A second differentially expressed gene encoding stearoyl-CoA desaturase. The Journal of biological chemistry 264, 14755-14761. Kang, N., Gores, G.J., Shah, V.H., 2011. Hepatic stellate cells: partners in crime for liver metastases? Hepatology 54, 707-713. Kaplowitz, N., 2001. Drug-induced liver disorders: implications for drug development and regulation. Drug safety : an international journal of medical toxicology and drug experience 24, 483-490. Kaplowitz, N., 2005. Idiosyncratic drug hepatotoxicity. Nature reviews. Drug discovery 4, 489-499. Kim, H.E., Bae, E., Jeong, D.Y., Kim, M.J., Jin, W.J., Park, S.W., Han, G.S., Carman, G.M., Koh, E., Kim, K.S., 2013. Lipin1 regulates PPARgamma transcriptional activity. The Biochemical journal 453, 49-60. Kleiner, D.E., Brunt, E.M., Van Natta, M., Behling, C., Contos, M.J., Cummings, O.W., Ferrell, L.D., Liu, Y.C., Torbenson, M.S., Unalp-Arida, A., Yeh, M., McCullough, A.J., Sanyal, A.J., Nonalcoholic Steatohepatitis Clinical Research, N., 2005. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 41, 1313-1321. Kliewer, S.A., Sundseth, S.S., Jones, S.A., Brown, P.J., Wisely, G.B., Koble, C.S., Devchand, P., Wahli, W., Willson, T.M., Lenhard, J.M., Lehmann, J.M., 1997. Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors alpha and gamma. Proceedings of the National Academy of Sciences of the United States of America 94, 4318-4323. Knapp, A.C., Todesco, L., Beier, K., Terracciano, L., Sagesser, H., Reichen, J., Krahenbuhl, S., 2008. Toxicity of valproic acid in mice with decreased plasma and tissue carnitine stores. The Journal of pharmacology and experimental therapeutics 324, 568-575. Koonen, D.P., Jacobs, R.L., Febbraio, M., Young, M.E., Soltys, C.L., Ong, H., Vance, D.E., Dyck, J.R., 2007. Increased hepatic CD36 expression contributes to dyslipidemia associated with diet-induced obesity. Diabetes 56, 2863-2871. Kuwasako, T., Hirano, K., Sakai, N., Ishigami, M., Hiraoka, H., Yakub, M.J., Yamauchi-Takihara, K., Yamashita, S., Matsuzawa, Y., 2003. Lipoprotein abnormalities in human genetic CD36 deficiency associated with insulin resistance and abnormal fatty acid metabolism. Diabetes care 26, 1647-1648. Lee, M.H., Hong, I., Kim, M., Lee, B.H., Kim, J.H., Kang, K.S., Kim, H.L., Yoon, B.I., Chung, H., Kong, G., Lee, M.O., 2007. Gene expression profiles of murine fatty liver induced by the administration of valproic acid. Toxicology and applied pharmacology 220, 45-59. Lee, M.H., Kim, M., Lee, B.H., Kim, J.H., Kang, K.S., Kim, H.L., Yoon, B.I., Chung, H., Kong, G., Lee, M.O., 2008. Subchronic effects of valproic acid on gene expression profiles for lipid metabolism in mouse liver. Toxicology and applied pharmacology 226, 271-284. Lee, W.M., 2003. Drug-induced hepatotoxicity. The New England journal of medicine 349, 474-485. Leone, T.C., Weinheimer, C.J., Kelly, D.P., 1999. A critical role for the peroxisome proliferator-activated receptor alpha (PPARalpha) in the cellular fasting response: the PPARalpha-null mouse as a model of fatty acid oxidation disorders. Proceedings of the National Academy of Sciences of the United States of America 96, 7473-7478. Lheureux, P.E., Penaloza, A., Zahir, S., Gris, M., 2005. Science review: carnitine in the treatment of valproic acid-induced toxicity - what is the evidence? Critical care 9, 431-440. Li, L.O., Ellis, J.M., Paich, H.A., Wang, S., Gong, N., Altshuller, G., Thresher, R.J., Koves, T.R., Watkins, S.M., Muoio, D.M., Cline, G.W., Shulman, G.I., Coleman, R.A., 2009. Liver-specific loss of long chain acyl-CoA synthetase-1 decreases triacylglycerol synthesis and beta-oxidation and alters phospholipid fatty acid composition. The Journal of biological chemistry 284, 27816-27826. Liang, G., Yang, J., Horton, J.D., Hammer, R.E., Goldstein, J.L., Brown, M.S., 2002. Diminished hepatic response to fasting/refeeding and liver X receptor agonists in mice with selective deficiency of sterol regulatory element-binding protein-1c. The Journal of biological chemistry 277, 9520-9528. Loscher, W., 2002. Basic pharmacology of valproate: a review after 35 years of clinical use for the treatment of epilepsy. CNS drugs 16, 669-694. Lucena, M.I., Andrade, R.J., Kaplowitz, N., Garcia-Cortes, M., Fernandez, M.C., Romero-Gomez, M., Bruguera, M., Hallal, H., Robles-Diaz, M., Rodriguez-Gonzalez, J.F., Navarro, J.M., Salmeron, J., Martinez-Odriozola, P., Perez-Alvarez, R., Borraz, Y., Hidalgo, R., Spanish Group for the Study of Drug-Induced Liver, D., 2009. Phenotypic characterization of idiosyncratic drug-induced liver injury: the influence of age and sex. Hepatology 49, 2001-2009. Luef, G.J., Waldmann, M., Sturm, W., Naser, A., Trinka, E., Unterberger, I., Bauer, G., Lechleitner, M., 2004. Valproate therapy and nonalcoholic fatty liver disease. Annals of neurology 55, 729-732. Luiken, J.J., Koonen, D.P., Willems, J., Zorzano, A., Becker, C., Fischer, Y., Tandon, N.N., Van Der Vusse, G.J., Bonen, A., Glatz, J.F., 2002. Insulin stimulates long-chain fatty acid utilization by rat cardiac myocytes through cellular redistribution of FAT/CD36. Diabetes 51, 3113-3119. MacPhee, P.J., Schmidt, E.E., Groom, A.C., 1992. Evidence for Kupffer cell migration along liver sinusoids, from high-resolution in vivo microscopy. The American journal of physiology 263, G17-23. Marion-Letellier, R., Dechelotte, P., Iacucci, M., Ghosh, S., 2009. Dietary modulation of peroxisome proliferator-activated receptor gamma. Gut 58, 586-593. Martin, G., Schoonjans, K., Lefebvre, A.M., Staels, B., Auwerx, J., 1997. Coordinate regulation of the expression of the fatty acid transport protein and acyl-CoA synthetase genes by PPARalpha and PPARgamma activators. The Journal of biological chemistry 272, 28210-28217. Martins, I.J., Hone, E., Chi, C., Seydel, U., Martins, R.N., Redgrave, T.G., 2000. Relative roles of LDLr and LRP in the metabolism of chylomicron remnants in genetically manipulated mice. Journal of lipid research 41, 205-213. Mascaro, C., Acosta, E., Ortiz, J.A., Marrero, P.F., Hegardt, F.G., Haro, D., 1998. Control of human muscle-type carnitine palmitoyltransferase I gene transcription by peroxisome proliferator-activated receptor. The Journal of biological chemistry 273, 8560-8563. Mashek, D.G., Li, L.O., Coleman, R.A., 2006. Rat long-chain acyl-CoA synthetase mRNA, protein, and activity vary in tissue distribution and in response to diet. Journal of lipid research 47, 2004-2010. Masuda, D., Hirano, K., Oku, H., Sandoval, J.C., Kawase, R., Yuasa-Kawase, M., Yamashita, Y., Takada, M., Tsubakio-Yamamoto, K., Tochino, Y., Koseki, M., Matsuura, F., Nishida, M., Kawamoto, T., Ishigami, M., Hori, M., Shimomura, I., Yamashita, S., 2009. Chylomicron remnants are increased in the postprandial state in CD36 deficiency. Journal of lipid research 50, 999-1011. Matteoni, C.A., Younossi, Z.M., Gramlich, T., Boparai, N., Liu, Y.C., McCullough, A.J., 1999. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology 116, 1413-1419. May, P., Woldt, E., Matz, R.L., Boucher, P., 2007. The LDL receptor-related protein (LRP) family: an old family of proteins with new physiological functions. Annals of medicine 39, 219-228. McGarry, J.D., Brown, N.F., 1997. The mitochondrial carnitine palmitoyltransferase system. From concept to molecular analysis. European journal of biochemistry / FEBS 244, 1-14. McGarry, J.D., Leatherman, G.F., Foster, D.W., 1978. Carnitine palmitoyltransferase I. The site of inhibition of hepatic fatty acid oxidation by malonyl-CoA. The Journal of biological chemistry 253, 4128-4136. McMillian, M.K., Grant, E.R., Zhong, Z., Parker, J.B., Li, L., Zivin, R.A., Burczynski, M.E., Johnson, M.D., 2001. Nile Red binding to HepG2 cells: an improved assay for in vitro studies of hepatosteatosis. In vitro & molecular toxicology 14, 177-190. Mei, S., Ni, H.M., Manley, S., Bockus, A., Kassel, K.M., Luyendyk, J.P., Copple, B.L., Ding, W.X., 2011. Differential roles of unsaturated and saturated fatty acids on autophagy and apoptosis in hepatocytes. The Journal of pharmacology and experimental therapeutics 339, 487-498. Migita, T., Ruiz, S., Fornari, A., Fiorentino, M., Priolo, C., Zadra, G., Inazuka, F., Grisanzio, C., Palescandolo, E., Shin, E., Fiore, C., Xie, W., Kung, A.L., Febbo, P.G., Subramanian, A., Mucci, L., Ma, J., Signoretti, S., Stampfer, M., Hahn, W.C., Finn, S., Loda, M., 2009. Fatty acid synthase: a metabolic enzyme and candidate oncogene in prostate cancer. Journal of the National Cancer Institute 101, 519-532. Miyazaki, M., Dobrzyn, A., Man, W.C., Chu, K., Sampath, H., Kim, H.J., Ntambi, J.M., 2004. Stearoyl-CoA desaturase 1 gene expression is necessary for fructose-mediated induction of lipogenic gene expression by sterol regulatory element-binding protein-1c-dependent and -independent mechanisms. The Journal of biological chemistry 279, 25164-25171. Miyazaki, M., Jacobson, M.J., Man, W.C., Cohen, P., Asilmaz, E., Friedman, J.M., Ntambi, J.M., 2003. Identification and characterization of murine SCD4, a novel heart-specific stearoyl-CoA desaturase isoform regulated by leptin and dietary factors. The Journal of biological chemistry 278, 33904-33911. Miyazaki, M., Kim, H.J., Man, W.C., Ntambi, J.M., 2001. Oleoyl-CoA is the major de novo product of stearoyl-CoA desaturase 1 gene isoform and substrate for the biosynthesis of the Harderian gland 1-alkyl-2,3-diacylglycerol. The Journal of biological chemistry 276, 39455-39461. Miyazaki, M., Kim, Y.C., Gray-Keller, M.P., Attie, A.D., Ntambi, J.M., 2000. The biosynthesis of hepatic cholesterol esters and triglycerides is impaired in mice with a disruption of the gene for stearoyl-CoA desaturase 1. The Journal of biological chemistry 275, 30132-30138. Monti, B., Polazzi, E., Contestabile, A., 2009. Biochemical, molecular and epigenetic mechanisms of valproic acid neuroprotection. Current molecular pharmacology 2, 95-109. Munday, M.R., Hemingway, C.J., 1999. The regulation of acetyl-CoA carboxylase--a potential target for the action of hypolipidemic agents. Advances in enzyme regulation 39, 205-234. Musso, G., Gambino, R., Cassader, M., 2009. Recent insights into hepatic lipid metabolism in non-alcoholic fatty liver disease (NAFLD). Progress in lipid research 48, 1-26. Najjar, S.M., Yang, Y., Fernstrom, M.A., Lee, S.J., Deangelis, A.M., Rjaily, G.A., Al-Share, Q.Y., Dai, T., Miller, T.A., Ratnam, S., Ruch, R.J., Smith, S., Lin, S.H., Beauchemin, N., Oyarce, A.M., 2005. Insulin acutely decreases hepatic fatty acid synthase activity. Cell metabolism 2, 43-53. Nalivaeva, N.N., Belyaev, N.D., Turner, A.J., 2009. Sodium valproate: an old drug with new roles. Trends in pharmacological sciences 30, 509-514. Natarajan, S.K., Eapen, C.E., Pullimood, A.B., Balasubramanian, K.A., 2006. Oxidative stress in experimental liver microvesicular steatosis: role of mitochondria and peroxisomes. Journal of gastroenterology and hepatology 21, 1240-1249. Ntambi, J.M., Buhrow, S.A., Kaestner, K.H., Christy, R.J., Sibley, E., Kelly, T.J., Jr., Lane, M.D., 1988. Differentiation-induced gene expression in 3T3-L1 preadipocytes. Characterization of a differentially expressed gene encoding stearoyl-CoA desaturase. The Journal of biological chemistry 263, 17291-17300. Ntambi, J.M., Miyazaki, M., Stoehr, J.P., Lan, H., Kendziorski, C.M., Yandell, B.S., Song, Y., Cohen, P., Friedman, J.M., Attie, A.D., 2002. Loss of stearoyl-CoA desaturase-1 function protects mice against adiposity. Proceedings of the National Academy of Sciences of the United States of America 99, 11482-11486. Oikawa, E., Iijima, H., Suzuki, T., Sasano, H., Sato, H., Kamataki, A., Nagura, H., Kang, M.J., Fujino, T., Suzuki, H., Yamamoto, T.T., 1998. A novel acyl-CoA synthetase, ACS5, expressed in intestinal epithelial cells and proliferating preadipocytes. Journal of biochemistry 124, 679-685. Olson, M.J., Handler, J.A., Thurman, R.G., 1986. Mechanism of zone-specific hepatic steatosis caused by valproate: inhibition of ketogenesis in periportal regions of the liver lobule. Molecular pharmacology 30, 520-525. Ostapowicz, G., Fontana, R.J., Schiodt, F.V., Larson, A., Davern, T.J., Han, S.H., McCashland, T.M., Shakil, A.O., Hay, J.E., Hynan, L., Crippin, J.S., Blei, A.T., Samuel, G., Reisch, J., Lee, W.M., Group, U.S.A.L.F.S., 2002. Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Annals of internal medicine 137, 947-954. Patsouris, D., Reddy, J.K., Muller, M., Kersten, S., 2006. Peroxisome proliferator-activated receptor alpha mediates the effects of high-fat diet on hepatic gene expression. Endocrinology 147, 1508-1516. Pessayre, D., Fromenty, B., Berson, A., Robin, M.A., Letteron, P., Moreau, R., Mansouri, A., 2012. Central role of mitochondria in drug-induced liver injury. Drug metabolism reviews 44, 34-87. Peterson, G.M., Naunton, M., 2005. Valproate: a simple chemical with so much to offer. Journal of clinical pharmacy and therapeutics 30, 417-421. Petronijevic, M., Ilic, K., 2013. Associations of gender and age with the reporting of drug-induced hepatic failure: data from the VigiBase. Journal of clinical pharmacology 53, 435-443. Pi, J., Bai, Y., Daniel, K.W., Liu, D., Lyght, O., Edelstein, D., Brownlee, M., Corkey, B.E., Collins, S., 2009. Persistent oxidative stress due to absence of uncoupling protein 2 associated with impaired pancreatic beta-cell function. Endocrinology 150, 3040-3048. Pourahmad, J., Eskandari, M.R., Kaghazi, A., Shaki, F., Shahraki, J., Fard, J.K., 2012. A new approach on valproic acid induced hepatotoxicity: involvement of lysosomal membrane leakiness and cellular proteolysis. Toxicology in vitro : an international journal published in association with BIBRA 26, 545-551. Price, N.T., van der Leij, F.R., Jackson, V.N., Corstorphine, C.G., Thomson, R., Sorensen, A., Zammit, V.A., 2002. A novel brain-expressed protein related to carnitine palmitoyltransferase I. Genomics 80, 433-442. Qiao, L., Schaack, J., Shao, J., 2006. Suppression of adiponectin gene expression by histone deacetylase inhibitor valproic acid. Endocrinology 147, 865-874. Raabe, M., Veniant, M.M., Sullivan, M.A., Zlot, C.H., Bjorkegren, J., Nielsen, L.B., Wong, J.S., Hamilton, R.L., Young, S.G., 1999. Analysis of the role of microsomal tri | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/60939 | - |
| dc.description.abstract | Valproic acid (VPA) 是現今臨床治療癲癇的處方用藥，為人工合成之支鏈脂肪酸，使用在臨床治療已長達35年以上。除了用於治療癲癇外，VPA在臨床上的使用非常廣泛，例如治療躁鬱症、預防偏頭痛、穩定情緒、治療神經退化相關疾病如阿茲海默症等，且因其為組織蛋白去乙醯酶抑制劑，可能具有抗癌潛力。此外，相較於其他抗癲癇藥物，VPA對病患而言耐受度較高、副作用較少，種種優點使得VPA在臨床上具有相當的優勢。然而，其仍具有副作用如導致病患體重增加、肝臟脂質浸潤 (hepatic steatosis) 及致死性肝衰竭 (fatal liver injury) 等。根據臨床統計指出，約有六成病患服用VPA而造成hepatic steatosis，然而其機制仍未完全明瞭。因此，本研究的目的為探討VPA 可能造成肝臟脂質浸潤的機制。
本研究使用小鼠肝臟細胞株FL83B細胞，以in vitro模式探討VPA造成脂質堆積的可能機制。以real-time PCR進行基因表現量分析結果顯示，VPA與18碳單鍵不飽和脂肪酸 (oleic acid, OA) 共處理組之Perilipin2 (為合成油滴必須之表面蛋白) 表現量增加。脂肪酸轉位酶Cd36在VPA單處理及共處理組別中表現量均增加，顯示此基因可能受到VPA調控。此外，合成三酸甘油脂 (triacylglycerol，TAG) 最後步驟所需之限制速率酵素Dgat2, 表現量也在VPA處理下顯著提升。而與脂肪酸合成相關酵素Accα 及 Fasn, 在VPA處理組的表現量則受到抑制。顯示VPA可能是透過增加胞外攝入的脂肪酸含量，促使其合成TAG，並增加Perilipin2表現，使油滴大量堆積在細胞質中。儘管調控CD36表現的轉錄因子脂小體增生活化受體γ (peroxisome proliferator-activated receptor γ, PPARγ) 基因及蛋白質表現量變化發現並無顯著差異；但螢光免疫染色結果觀察到其表現位置大幅轉移至細胞核中，可能暗示其被活化後進入細胞核中而造成下游基因被轉錄。CD36表現量在共處理及VPA單處理的情況下均有所增加，而部分蛋白質則從細胞質內轉至細胞膜上，推測其可能增加細胞膜上的脂肪酸運輸。 綜上所述，VPA增加肝臟細胞脂質堆積的可能機制為透過PPARγ轉移至細胞核內，造成下游CD36基因表現量增加，並進而造成脂肪酸攝入量大幅提升；同時藉由Dgat2表現量增加使得TAG產量增加，致使油滴大量堆積在肝臟細胞質內。然而，其中詳細的調控機制，仍須更進一步試驗來釐清。 | zh_TW |
| dc.description.abstract | Valproic acid (VPA) is an antiepilepsy drug with broadest spectrum used in all types of epileptic seizures for more than 40 years in human medicine. It’s also commonly prescribed to treat bipolar disorder, neuropathic pain, migraine headache, and central nervous system (CNS) diseases. Although VPA is successfully applied to clinics for decades, it has been reported that VPA treatment also cause some adverse effects such as weight gain, hepatic steatosis and fatal liver injury. About 60 % of patients who received VPA monotherapy gained hepatic steatosis with higher BMI values. In this study, we aimed to explore the possible mechanisms of VPA-induced hepatic steatosis.
To figure out the possible mechanisms of VPA-induced hepatic steatosis, mouse hepatocyte FL83B cell line was used to study the mechanism of VPA-induced hepatic steatosis in vitro. As the results of real-time PCR, VPA treatment increased the expression of Perilipin2, which encodes a lipid droplet protein. VPA also significantly enhanced Fat/Cd36 which transports fatty-acid across the cell membrane; moreover, it elevates Dgat2, an enzyme that catalyzes the final step of triacylglycerol synthesis. Meanwhile, genes related to fatty-acid synthesis such as Accα and Fasn, were both down-regulated compared to OA-treatment which may imply that the fatty-acid synthesis does not contribute to VPA-enhanced hepatic steatosis. Since CD36 is a direct target of peroxisome proliferator-activated receptor gamma (PPARγ), a transcriptional factor that regulates lipogenesis, protein expressions of CD36 and PPARγ were analyzed by flow cytometry. Consequently, protein expression of CD36 was enhanced by VPA; whereas both mRNA and protein expression of PPARγ were unchanged. However, immunocytochemistry was used to evaluate the protein location of PPARγ. The results showed that PPARγ translocated from cytoplasm to nucleus in OA, VPA and co-treatment group. Additionally, CD36 translocated from cytoplasm to membrane in OA and co-treatment group. In summary, VPA may enhance lipid accumulation in hepatocytes through increasing fatty-acid uptake by enhancing PPARγ translocation and CD36 expression; simultaneously, DGAT2 was elevated to increase triacylglycerol synthesis. However, further studies need to perform to elucidate the mechanisms of VPA-induced hepatic steatosis in detail. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T10:37:27Z (GMT). No. of bitstreams: 1 ntu-102-R00626004-1.pdf: 1479486 bytes, checksum: ccb5d86ae3b2b66b237750d9e1bfa138 (MD5) Previous issue date: 2013 | en |
| dc.description.tableofcontents | 摘要 I
Abstract II TABLE OF CONTENTS IV LIST OF FIGURES VI LIST OF TABLES VII ABBREVATIONS VIII Chapter 1 Introduction 1 1.1 Drug-induced liver injury (DILI) 2 1.2 Liver 3 1.3 Hepatic steatosis 4 1.4 Liver lipid metabolism 6 1.5 Valproic acid 18 Chapter 2 Materials and Methods 22 2.1 Chemicals 22 2.2 Cell culture 22 2.3 Lipid accumulation 22 2.4 Cell viability 23 2.5 Real-time PCR 24 2.6 Immunocytochemistry 29 2.7 Flow cytometry 29 2.8 Statistical analysis 30 Chapter 3 Results 31 3.1 Effects of treating different concentrations of oleic acid on lipid accumulation in FL83B cells 31 3.2 Effects of valproic acid on lipid accumulation in FL83B cells 34 3.3 Effects of different VPA concentrations under 100 μM OA co-treatment on cell viability 37 3.4 Effects of VPA and VPA co-treatment with OA on gene expression 40 3.5 Effects of VPA on protein expression and location of PPARγ and CD36 48 Chapter 4 Discussion 54 4.1 Induced lipid accumulation in FL83B cells 55 4.2 Possible mechanisms that VPA-enhanced lipid accumulation in FL83B cells 56 Chapter 5 References 60 | |
| dc.language.iso | en | |
| dc.title | 丙戊酸(Valproic acid)造成肝臟細胞脂質堆積機制探討 | zh_TW |
| dc.title | Valproic acid induces lipid accumulation in hepatocytes by regulating lipid transportation | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 101-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.coadvisor | 陳億乘(Chen-Yi Chen) | |
| dc.contributor.oralexamcommittee | 吳兩新(Leang-Shin Wu),周崇熙(Chung-Hsi Chou),謝淑貞(Shu-Chen Hsieh) | |
| dc.subject.keyword | 丙戊酸,脂肪酸轉位酶,脂小體增生活化受體γ,肝臟脂質浸潤,脂質運輸, | zh_TW |
| dc.subject.keyword | valproic acid,CD36,PPARγ,hepatic steatosis,lipid transportation, | en |
| dc.relation.page | 85 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2013-08-14 | |
| dc.contributor.author-college | 生物資源暨農學院 | zh_TW |
| dc.contributor.author-dept | 動物科學技術學研究所 | zh_TW |
| 顯示於系所單位： | 動物科學技術學系 | |
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