請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/64673
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 陳小梨(Show-Li Chen) | |
dc.contributor.author | Wan-Lun Yan | en |
dc.contributor.author | 嚴婉倫 | zh_TW |
dc.date.accessioned | 2021-06-16T22:57:12Z | - |
dc.date.available | 2017-09-19 | |
dc.date.copyright | 2012-09-19 | |
dc.date.issued | 2012 | |
dc.date.submitted | 2012-08-09 | |
dc.identifier.citation | Allen, D.G., Lee, J.A., Westerblad, H. 1989. Intracellular calcium and tension during fatigue in isolated single muscle fibres from Xenopus laevis. J. Physiol. 415:433-458.
Allen, D.G., Westerblad, H. 2001. Role of phosphate and calcium stores in muscle fatigue. J. Physiol. 536:657–665. Axell, A.M., MacLean, H.E., Plant, D.R., Harcourt, L.J., Davis, J.A., Jimenez, M., Handelsman, D.J., Lynch, G.S., Zajac, J.D. 2006. Continuous testosterone administration prevents skeletal muscle atrophy and enhances resistance to fatigue in orchidectomized male mice. Am. J. Physiol. Endocrinol. Metab. 291:E506-E516. Babu, Y.S., Bugg, C.E., Cook, W.J. 1988. Structure of calmodulin refined at 2.2 A resolution. J. Mol. Biol. 204:191–204. Bassel-Duby, R., and Olson, E.N. 2006. Signaling pathways in skeletal muscle remodeling. Annu. Rev. Biochem. 75:19–37 Berchtold, M.W., Brinkmeier, H., Müntener, M. 2000. Calcium ion in skeletal muscle: its crucial role for muscle function, plasticity, and disease. Physiol. Rev. 80:1215-1265. Bigland-Ritchie, B., Johansson, R., Lippold, O.C., Woods, J.J. 1983. Contractile speed and EMG changes during fatigue of sustained maximal voluntary contractions. J. Neurophysiol. 50:313-324. Blau, H. M., Chiu, C. P. and Webster, C. 1983. Cytoplasmic activation of human nuclear genes in stable heterocaryons. Cell. 32:1171-1180. Buch, M.H., Pickard, A., Rodriguez, A., Gillies, S., Maass, A.H., Emerson, M., Cartwright, E.J., Williams, J.C., Oceandy, D., Redondo, J.M., Neyses, L., Armesilla, A.L. 2005.The sarcolemmal calcium pump inhibits the calcineurin/nuclear factor of activated T-cell pathway via interaction with the calcineurin A catalytic subunit. J. Biol. Chem. 280:29479–29487. Brummelkamp, T.R., Bernards, R., Agami, R. 2002. A system for stable expression of short interfering RNAs in mammalian cells. Science. 296:550-553. Burattini, S., Ferri, P., Battistelli, M., Curci, R., Luchetti, F., Falcieri, E. 2004. C2C12 murine myoblasts as a model of skeletal muscle development: morpho-functional characterization. Eur. J. Histochem. 48:223-233. Bowman, W.C. 2006. Neuromuscular block. Br. J. Pharmacol. 147:S277-S286. Cairns, S.P., Robinson, D.M., Loiselle, D.S. 2008. Double-sigmoid model for fitting fatigue profiles in mouse fast- and slow-twitch muscle. Exp. Physiol. 93:851-62. Cairns, S.P., Taberner, A.J., Loiselle, D.S. 2009. Changes of surface and t-tubular membrane excitability during fatigue with repeated tetani in isolated mouse fast- and slow-twitch muscle. J. Appl. Physiol. 106:101-112. Chang, S.W., Tsao, Y.P., Lin, C.Y., Chen, S.L. 2011. NRIP, a novel calmodulin binding protein, activates calcineurin to dephosphorylate human papillomavirus E2 protein. J. Virol. 85:6750-6763. Chattopadhyaya, R., Meador, W.E., Means, A.R., Quiocho, F.A. 1992. Calmodulin structure refined at 1.7 A resolution. J. Mol. Biol. 228:1177–1192. Chen, P. H., Y. P. Tsao, C. C. Wang, and S. L. Chen. 2008. Nuclear receptor interaction protein, a coactivator of androgen receptors (AR), is regulated by AR and Sp1 to feed forward and activate its own gene expression through AR protein stability. Nucleic Acids Res. 36:51–66. Chin, E.R., Allen, D.G. 1996. The role of elevations in intracellular [Ca2+] in the development of low frequency fatigue in mouse single muscle fibres. J. Physiol. 491 (Pt. 3): 813-824. Chin, E.R., Olson, E.N., Richardson, J.A., Yang, Q., Humphries, C., Shelton, J.M., Wu, H., Zhu, W., Bassel-Duby, R., Williams, R.S. 1998. A calcineurin- dependent transcriptional pathway controls skeletal muscle fiber type. Genes Dev. 12:2499-2509. Chin, E.R. 2004. The role of calcium and calcium/calmodulin-dependent kinases in skeletal muscle plasticity and mitochondrial biogenesis. Proc. Nutr. Soc.63: 279-286. Crabtree, G.R. 1999. Generic signals and specific outcomes: signaling through Ca2+, calcineurin, and NF-AT. Cell. 96:611-614. Delling, U., Tureckova, J., Lim, H.W., De, Windt, L.J., Rotwein, P., Molkentin J.D. 2000. A calcineurin-NFATc3-dependent pathway regulates skeletal muscle differentiationand slow myosin heavy-chain expression. Mol. Cell. Biol. 20:6600–6611. Ferrando, A.A., Sheffield-Moore, M., Yeckel, C.W., Gilkison, C., Jiang, J., Achacosa, A., Lieberman, S.A., Tipton, K., Wolfe, R.R., and Urban, R.J. 2002 Testosterone administration to older men improves muscle function: molecular and physiological mechanisms. Am. J. Physiol. Endocrinol. Metab. 282:E601–E607. Franke, W. W., Berendonk, B. 1997. Hormonal doping and androgenization of athletes: a secret program of the German Democratic Republic government. Clin. Chem. 43:1262-1279. Franzini-Armstrong, C., Protasi, F. 1997. Ryanodine receptors of striated muscles: a complex channel capable of multiple interactions. Physiol. Rev. 77: 699-729. Frey, N., Richardson, J.A., and Olson, E.N. 2000. Calsarcins, a novel family of sarcomeric calcineurin-binding proteins. Proc. Natl. Acad. Sci. U. S. A.97:14632–14637. Frey, N., Barrientos, T., Shelton, J.M., Frank, D., Rütten, H., Gehring, D., Kuhn, C., Lutz, M., Rothermel, B., Bassel-Duby, R., Richardson, J.A., Katus, H.A., Hill, J.A., Olson, E.N. 2004. Mice lacking calsarcin-1 are sensitized to calcineurin signaling and show accelerated cardiomyopathy in response to pathological biomechanical stress. Nat. Med. 10:1336-1343. Frey, N., Frank, D., Lippl, S., Kuhn, C., Kögler, H., Barrientos, T., Rohr, C., Will, R., Müller, O.J., Weiler, H., Bassel-Duby, R., Katus, H.A., Olson, E.N. 2008. Calsarcin-2 deficiency increases exercise capacity in mice through calcineurin/NFAT activation. J. Clin. Invest. 118:3598-3608. Fill, M., and Copello, J.A. 2002. Ryanodine receptor calcium release channels. Physiol. Rev. 82:893–922. Fulco, C.S., Rock, P.B., Muza, S.R., Lammi, E., Cymerman, A., Butterfield, G., Moore, L.G., Braun, B., Lewis, S.F. 1999. Slower fatigue and faster recovery of the adductor pollicis muscle in women matched for strength with men. Acta Physiol. Scand. 167:233–239. Furukawa, T., Ono, Y., Tsuchiya, H., Katayama, Y., Bang, M.L., Labeit, D., Labeit, S., Inagaki, N., Gregorio, C.C. 2001. Specific interaction of the potassium channel beta-subunit minK with the sarcomeric protein T-cap suggests a T-tubule-myofibril linking system. J. Mol. Biol. 313:775-784. Glenmark, B., Nilsson, M., Gao, H., Gustafsson, J.A., Dahlman-Wright, K., Westerblad, H. 2004. Difference in skeletal muscle function in males vs.females: role of estrogen receptor-β. Am. J. Physiol. Endocrinol. Metab. 287:E1125–E1131. Gosker, H.R., van, Mameren, H., van, Dijk, P.J., Engelen, M.P., van, der, Vusse, G.J., Wouters, E.F., Schols, A.M. 2002. Skeletal muscle fibre-type shifting and metabolic profile in patients with chronic obstructive pulmonary disease. Eur. Respir. J. 19:617-625. He, Y.J., McCall, C.M., Hu, J., Zeng, Y., Xiong, Y. 2006. DDB1 functions as a linker to recruit receptor WD40 proteins to CUL4-ROC1 ubiquitin ligases. Genes Dev. 20: 2949-2954. Heineke, J., Ruetten, H., Willenbockel, C., Gross, S.C., Naguib, M., Schaefer, A., Kempf, T., Hilfiker-Kleiner, D., Caroni, P., Kraft, T., Kaiser, R.A., Molkentin, J.D., Drexler, H., Wollert, K.C. 2005. Attenuation of cardiac remodeling after myocardial infarction by muscle LIM protein-calcineurin signaling at the sarcomeric Z-disc. Proc. Natl. Acad. Sci. U. S. A. 102:1655-1660. Hicks, A.L., Kent-Braun, J., Ditor, D.S. 2001. Sex differences in human skeletal muscle fatigue. Exerc. Sport. Sci. Rev. 29:109-112. Higa, L.A., Wu, M., Ye, T., Kobayashi, R., Sun, H., Zhang, H. 2006. CUL4-DDB1 ubiquitin ligase interacts with multiple WD40-repeat proteins and regulates histone methylation. Nat. Cell Biol. 2:1277-1283. Homsher, E. 1987. Muscle Enthalpy Production and ITS Relationship to Actomyosin ATPase. Annu. Rev. Physiol. 49:673-690. Hughes, S. M. 1998. Muscle development: Electrical control of gene expression. Curr. Biol. 8:R892–R894. Russ, D.W., Kent-Braun, J.A. 2003. Sex differences in human skeletal muscle fatigue are eliminated under ischemic conditions. J. Appl. Physiol. 94:2414-2422. Kingsbury, T.J., Cunningham, K.W. 2000. A conserved family of calcineurin regulators. Genes Dev. 14:1595–1604. Koenig, H., Goldstone, A., Lu, C.Y. 1980. Androgens regulate mitochondrial cytochrome c oxidase and lysosomal hydrolases in mouse skeletal muscle. Biochem. J. 192:349–353. Kubis, H.P., Scheibe, R.J., Meissner, J.D., Hornung, G., Gros, G. 2002. Fast-to-slow transformation and nuclear import/export kinetics of the transcription factor NFATc1 during electrostimulation of rabbit muscle cells in culture. J. Physiol. 541:835–847. Lanner, J.T., Georgiou, D.K., Joshi, A.D., Hamilton, S.L. 2010. Ryanodine receptors: structure, expression, molecular details, and function in calcium release. Cold. Spring. Harb. Perspect. Biol. 2:a003996. MacLean, H.E., Chiu, W.S., Notini, A.J., Axell, A.M., Davey, R.A., McManus, J.F., Ma, C., Plant, D.R., Lynch, G.S., Zajac, J.D. 2008. Impaired skeletal muscle development and function in male, but not female, genomic androgen receptor knockout mice. FASEB. J. 22:2676-2689. MacLean, H.E., Warne, G.L., Zajac, J.D. 1997. Localization of functional domains in the androgen receptor. J. Steroid. Biochem. Mol. Biol. 62:233–242. Maclntosh, B.R., Holash, R.J., Renaud, J.M. 2012. Skeletal muscle fatigue - regulation of excitation-contraction coupling to avoid metabolic catastrophe. J. Cell Sci. 125:2105-2114. Maughan, R.J., Harmon, M., Leiper, J.B., Sale, D., Delman, A., 1986. Endurance capacity of untrained males and females in isometric and dynamic muscular contractions. Eur. J. Appl. Physiol. 55:395–400. Mauras, N., Hayes, V., Welch, S., Rini, A., Helgeson, K., Dokler, M., Veldhuis, J. D., Urban, R. J. 1998. Testosterone deficiency in young men: marked alterations in whole body protein kinetics, strength, and adiposity. J. Clin. Endocrinol. Metab. 83:1886-1892 McKinsey, T.A., Zhang, C.L., Lu, J., Olson, E.N. 2000. Signal-dependent nuclear export of a histone deacetylase regulates muscle differentiation. Nature. 408:106-111. Meissner, J.D., Kubis, H.P., Scheibe, R.J., Gros, G. 2000. Reversible Ca2+-induced fast-to-slow transition in primary skeletal muscle culture cells at the mRNA level. J. Physiol. 523:19–28. Meissner, J.D., Freund, R., Krone, D., Umeda, P.K., Chang, K.C., Gros, G., Scheibe, R.J. 2011. Extracellular signal-regulated kinase 1/2-mediated phosphorylation of p300 enhances myosin heavy chain I/beta gene expression via acetylation of nuclear factor of activated T cells c1. Nucleic Acids Res. 39:5907-5925. Miller, A.E.J., MacDougall, J.D., Tarnopolsky, M.A., Sale, D.G. 1993. Gender differences in strength and muscle fibre characteristics. Eur. J. Appl. Physiol. 66:254 –262. Nakai, J., Sekiguchi, N., Rando,T.A., Allen, P.D., Beam, K.G. 1998. Two regions of the ryanodine receptor involved in coupling with L-type Ca2+ channels. J. Biol. Chem. 273:13403–13406. Naya, F.J., Mercer, B., Shelton, J., Richardson, J.A., Williams, R.S., Olson, E.N. 2000. Stimulation of slow skeletal muscle fiber gene expression by calcineurin in vivo. J. Biol. Chem. 275:4545-4548. Nixon, G.F., Mignery, G.A., Somlyo, A.V. 1994. Immunogold localization of inositol 1,4,5-trisphosphate receptors and characterization of ultrastructural features of the sarcoplasmic reticulum in phasic and tonic smooth muscle. J. Muscle Res. Cell Motil. 15: 682–700. Oh, M., Rybkin, I.I., Copeland, V., Czubryt, M.P., Shelton, J.M., van, Rooij, E., Richardson, J.A., Hill, J.A., De, Windt, L.J., Bassel-Duby, R., Olson, E.N., Rothermel, B.A. 2005. Calcineurin is necessary for the maintenance but not embryonic development of slow muscle fibers. Mol. Cell Biol. 25:6629-6638. Otsu, K., Willard, H.F., Khanna, V.K., Zorzato, F., Green, N.M., MacLennan, D.H. 1990. Molecular cloning of cDNA encoding the Ca2+ release channel (ryanodine receptor) of rabbit cardiac muscle sarcoplasmic reticulum. J. Biol. Chem. 265:13472–13483. Pearse, A.G. 1972. Histochemistry: Theoretical and applied. 3rd edition Edinburgh, Churchill Livingstone. Pette, D., and Vrbova, G. 1992. Adaptation of mammalian skeletal muscle fibers to chronic electrical stimulation. Rev. Physiol. Biochem. Pharmacol. 120:115–202. Pette, D., and Staron, R.S. 1997. Mammalian skeletal muscle fiber type transitions. Int. Rev. Cytol. 170:143-223. Potthoff, M.J., Wu, H., Arnold, M.A., Shelton, J.M., Backs, J., McAnally, J., Richardson, J.A., Bassel-Duby, R., Olson, E.N. 2007. Histone deacetylase degradation and MEF2 activation promote the formation of slow-twitch myofibers. J. Clin. Invest. 117:2459-2467. Prosser, B.L., Hernández-Ochoa, E.O., Lovering, R.M., Andronache, Z., Zimmer, D.B., Melzer, W., Schneider, M.F. 2010. S100A1 promotes action potential-initiated calcium release flux and force production in skeletal muscle. Am. J. Physiol. Cell Physiol. 299:C891-C902. Pyle, W.G., Solaro, R.J. 2004. At the Crossroads of Myocardial Signaling: The Role of Z-disc in Intracellular. Circ Res. 94:296-305. Rios, E., Brum, G.1987. Involvement of dihydropyridine receptors in excitation- contraction coupling in skeletal muscle. Nature. 325:717–720. Rothermel, B.A., Vega, R.B., Yang, J., Wu, H., Bassel-Duby, R., Williams, R.S. 2000. A protein encoded within the Down syndrome critical region is enriched in striated muscles and inhibits calcineurin signaling. J. Biol. Chem. 275:8719–8725. Rothermel, B.A., Vega, R.B., Williams, R.S. 2003. The role of modulatory calcineurin-interacting proteins in calcineurin signaling. Trends Cardiovasc Med. 13:15-21. Satoh, K., Gotoh, T., Yamashita, K. 2000. Morphological effects of an anabolic steroid on muscle fibres of the diaphragm in mice. J. Electron. Microsc. (Tokyo) 49:531–538. Salmons, S., and Sreter, F. A. 1976. Fast and slow myosin in developing muscle fibres. Nature. 263:30–34. Schaub, M.C,. Heizmann, C.W. 2008. Calcium, troponin, calmodulin, S100 proteins: from myocardial basics to new therapeutic strategies. Biochem. Biophys. Res. Commun. 369:247-64. Schiaffino, S., Hanzlikova, V., and Pierobon, S. 1970. Relations between structure and function in rat skeletal muscle fibers. J. Cell Biol. 47:107–119. Schiaffino, S., and Reggiani, C. 1996. Molecular diversity of myofibrillar proteins: gene regulation and functional significance. Physiol. Rev. 76:371-423. Schiaffino, S., and Reggiani, C. 2011. Fiber types in mammalian skeletal muscles. Physiol. Rev. 91:1447-1531. Schiaffino, S., Serrano, A. 2002. Calcineurin signaling and neural control of skeletal muscle fiber type and size. Trends. Pharmacol. Sci. 23:569-575 Schroeder, E.T., Terk, M., and Sattler, F.R. 2003. Androgen therapy improves muscle mass and strength but not muscle quality: results from two studies. Am. J. Physiol. Endocrinol. Metab. 285:E16-E24. Semmler, J.G., Kutzscher, D.V., Enoka, R.M. 1999. Gender differences in the fatigability of human skeletal muscle. J. Neurophysiol. 82:3590-3593. Simoneau, J.A., Lortie, G., Boulay, M.R., Thibault, M.C., Thériault, G., Bouchard, C. 1985. Skeletal muscle histochemical and biochemical characteristics in sedentary male and female subjects. Can. J. Physiol. Pharmacol. 63:30-35. Sinha-Hikim, I., Artaza, J., Woodhouse, L., Gonzalez-Cadavid, N., Singh, A.B., Lee, M.I., Storer, T.W., Casaburi, R., Shen, R., Bhasin, S. 2002. Testosterone-induced increase in muscle size in healthy young men is associated with muscle fiber hypertrophy. Am. J. Physiol. Endocrinol. Metab. 283:E154-E164. Stupka, N., Schertzer, J.D., Bassel-Duby, R., Olson, E.N., Lynch, G.S. 2008. Stimulation of calcineurin Aalpha activity attenuates muscle pathophysiology in mdx dystrophic mice. Am. J. Physiol. Regul. Integr. Comp. Physiol. 294:R983-R992. Soeller, C., Crossman, D., Gilbert, R., Cannell, M.B. 2007. Analysis of ryanodine receptor clusters in rat and human cardiac myocytes. Proc. Natl. Acad. Sci. U. S. A. 104: 14958-14963. Song, L.S., Sobie, E.A., McCulle, S., Lederer, W.J., Balke, C.W., Cheng, H. 2006. Orphaned ryanodine receptors in the failing heart. Proc. Natl. Acad. Sci. U. S. A. 103: 4305-4310. Talmadge, R.J. and Roy R.R.1993. Electrophoretic separation of rat skeletal muscle myosin heavy-chain isoforms. J. Appl. Physiol. 75: 2337-2340. Tarnopolsky, M.A. 1999. Gender Differences in Metabolism: Practical and Nutritional Implications. New York: CRC. Tripathy, A., Xu, L., Mann, G., and Meissner, G. 1995. Calmodulin activation and inhibition of skeletal muscle Ca2+ release channel (ryanodine receptor). Biophys. J. 69: 106–119. Tsai, T. C., Y. L. Lee, W. C. Hsiao, Y. P. Tsao, and S. L. Chen. 2005. NRIP, a novel nuclear receptor interaction protein, enhances the transcriptional activity of nuclear receptors. J. Biol. Chem. 280:20000–20009. Wang, C., Swerdloff, R.S., Iranmanesh, A., Dobs, A., Snyder, P.J., Cunningham, G., Matsumoto, A.M., Weber, T., Berman, N., and the Testosterone Gel Study Group. 2000. Transdermal testosterone gel improves sexual function, mood, muscle strength, and body composition parameters in hypogonadal men. J. Clin. Endocrinol. Metab. 85:2839–2853. Westerblad, H., Allen, D.G. 1991. Changes of myoplasmic calcium concentration during fatigue in single mouse muscle fibers. J. Gen. Physiol. 98:615–635. Witzemann, V., Schwarz, H., Koenen, M., Berberich, C., Villarroel, A., Wernig, A., Brenner, H.R., Sakmann, B. 1996. Acetylcholine receptor epsilon-subunit deletion causes muscle weakness and atrophy in juvenile and adult mice. Proc. Natl. Acad. Sci. U. S. A. 93:13286-13291. Wysocka, J., Swigut, T., Milne, T.A., Dou, Y., Zhang, X., Burlingame, A.L., Roeder, R,G., Brivanlou, A,H., Allis, C.D. 2005. WDR5 associates with histone H3 methylated at K4 and is essential for H3 K4 methylation and vertebrate development. Cell. 121:859-72. Yaffe, D., Saxel, O. 1977. Serial passaging and differentiation of myogenic cells isolated from dystrophic mouse muscle. Nature. 270:725-727. Yang, J., Rothermel, B., Vega, R.B., Frey, N., McKinsey, T.A., Olson, E.N., Bassel-Duby, R., Williams, R.S. 2000. Independent signals control expression of the calcineurin inhibitory proteins MCIP1 and MCIP2 in striated muscles. Circ. Res. 87:E61–E68. Yoshioka, M., Boivin, A., Ye, P., Labrie, F., St-Amand, J. 2006. Effects of dihydrotestosterone on skeletal muscle transcriptome in mice measured by serial analysis of gene expression. J. Mol. Endocrinol. 36:247-259. Yoshioka, M., Boivin, A., Bolduc, C., St-Amand, J. 2007. Gender difference of androgen actions on skeletal muscle transcriptome. J. Mol. Endocrinol. 39:119-133. Zalk, R., Lehnart, S.E., Marks, A.R. 2007. Modulation of the ryanodine receptor and intracellular calcium. Annu. Rev. Biochem. 76:367-385. Zhang, Y., Ye, J., Chen, D., Zhao, X., Xiao, X., Tai, S., Yang, W., Zhu, D. 2006. Differential expression profiling between the relative normal and dystrophic muscle tissues from the same LGMD patient. J. Transl. Med. 4:53. Zuhlke, R.D., Pitt, G.S., Deisseroth, K., Tsien, R.W., and Reuter, H. 1999. Calmodulin supports both inactivation and facilitation of L-type calcium channels. Nature. 399:59–62. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/64673 | - |
dc.description.abstract | 我們實驗室發現了一個新的基因命名為核受體交互作用蛋白(Nuclear receptor interaction protein, NRIP),發現其為一種男性荷爾蒙接受器(Androgen receptor, AR)和質固醇受體(Glucocorticoid receptor, GR)的互動蛋白。NRIP的基因表現會受到AR所調控,在功能上NRIP可加強AR下游所調控基因的表現,並增加AR蛋白質的穩定性。除此之外,NRIP亦是攜鈣素(calmodulin, CaM)的結合蛋白。在鈣離子存在時,NRIP可藉由它結構上的IQ 模組直接與CaM結合進而活化鈣調磷酸酶(calcineurin)。活化後的calcineurin會對下游的調控蛋白質NFAT (nuclear factor of activated T cells)進行去磷酸化,使NFAT進入細胞核內,開啟一系列氧化能力高的慢收縮肌纖維基因的表現。現今已有文獻證實細胞內的鈣離子增加會活化calcineurin-NFAT訊息傳遞路徑,促進肌凝蛋白重鏈(myosin heavy chain)亞型之間的基因表現由快縮肌轉變成慢縮肌; 然而,現今對於調控快縮肌的基因表現機轉尚未明瞭。先前實驗室發現NRIP基因在骨骼肌中大量表現,此外NRIP剔除鼠在滾輪測試和跑步機的運動試驗上表現能力下降。根據2006年的報導指出,臨床上利用微陣分析(microarray assay)發現肢帶型肌肉萎縮症患者(Limb Girdle Muscular Dystrophy, 簡稱LGMD)缺乏NRIP基因的表現。因此我們利用NRIP剔除鼠探討NRIP在骨骼肌功能中所扮演的角色,並進一步探討NRIP引起肌肉無力的機轉。
首先,我們證明NRIP和calcineurin共同位於橫紋肌肌節的Z盤(Z-disc)上。此外,在離體肌肉收縮實驗中,當存有神經肌肉阻斷劑箭毒素(d-Tubocurarine)的條件下,NRIP剔除的公鼠和母鼠其比目魚肌(soleus,屬慢縮肌)的肌肉收縮力較各自的正常鼠弱;並且在連續電擊刺激下,公和母的NRIP剔除鼠肌肉的耐受力較正常鼠差。這些結果表示NRIP剔除的公母鼠其肌肉在功能表現上有缺陷。除此之外,無論NRIP剔除與否,母鼠維持肌耐力的能力皆比公鼠高。 根據2008年Stupka等人的報導,活化calcineurin會使氧化能力高的慢縮肌表現上升,進而增加肌耐力。因此接著分析在剔除鼠中calcineurin活性與肌凝蛋白重鏈的組成。結果顯示NRIP剔除鼠中的calcineurin-NFAT訊息傳遞的報告基因modulatory calcineurin interacting protein 1.4 (MCIP1.4)和慢縮肌凝重鏈蛋白的表現皆下降。同時,藉由小干擾RNA (siRNA)在細胞中抑制NRIP的表現也進一步驗證在老鼠骨骼肌肉組織中觀察到的結果。因此NRIP可能藉由calcineurin-NFAT的訊息傳遞路徑而影響肌肉功能的表現。 | zh_TW |
dc.description.abstract | NRIP, nuclear receptor interacting protein, is a novel gene that we identified previously. NRIP is a ligand-dependent coactivator of androgen receptor and glucocorticoid receptor. Also, NRIP is a Ca2+-dependent calmodulin binding protein (Ca+2/CaM), and it activates calcineurin phosphatase activity. Calcineurin is a serine/threonine protein phosphatase and localizes at sarcomeric Z-disc. The calcineurin-NFAT signaling pathway plays an essential role in fiber type transition promoting oxidative slow type myofibers expression in response to calcium waves. We previously found that the mRNA transcripts (Tsai et al., 2005) and protein expression of NRIP are abundant in skeletal muscle (Hsing-Hsung, thesis). Moreover, NRIP deficient mice exhibit decreased exercise performance on rotarod and treadmill tests (Hsing-Hsung thesis). Therefore, we hypothesize NRIP may play an important role in muscle strength and endurance performance.
In this study, we first demonstrated NRIP co-localizes with calcineurin at sarcomeric Z-disc by immunofluorescence assay. Specifically, slow-twitch soleus muscles of male and female NRIP-null mice significantly display impaired muscle function by in vitro muscle contraction assay, which the results show: 1) a reduced contractile force output in the present of neuromuscular blocker d-Tubocurarine to exclude the nerve activity, and 2) lower fatigue resistance compared to their counterpart NRIP+/+ controls. However, female soleus muscles exhibit higher fatigue resistance compared to males regardless of NRIP expression, suggesting muscle fatigue is gender-related. Based on Stupka et al (2008), calcineurin activation enhances hindlimb muscles endurance by promoting slow oxidative phenotype. Hence, calcineurin activity and fiber type composition were further examined. NRIP-/- muscles show a decrease in mRNA expression of calcineurin-NFATc1 reporter gene, MCIP1.4, and a reduced number of type I slow myosin. To further verify whether NRIP modulates slow myosin expression, mouse C2C12 myoblasts with siNRIP knockdown confirmed a reduced expression of MCIP1.4 and type I slow myosin, indicating a downregulation of calcineurin- NFATc1 signaling in vivo. Taken together, these results suggest that NRIP involves in skeletal muscle exercise performance through regulation of calcineurin-NFAT signaling pathway. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T22:57:12Z (GMT). No. of bitstreams: 1 ntu-101-R99445104-1.pdf: 2208054 bytes, checksum: 2ba4cb6521bdb36ff2bb18d9fe346b38 (MD5) Previous issue date: 2012 | en |
dc.description.tableofcontents | TABLE OF CONTENTS
口試委員審定書 致謝 i 中文摘要 ii ABSTRACT iv CHAPTER 1 INTRODUCTION 1 1.1 Properties of Adult Skeletal Muscle 1 1.2 Ca2+ Signaling in Skeletal Muscle 3 1.2.1 Mechanism of Muscle Contraction 3 1.2.2 Signal Pathway Involved in Fiber-Type Transition 5 1.3 The Characteristic of Nuclear Receptor Interaction Protein (NRIP) 8 1.4 Aim of the Thesis 9 CHAPTER 2 MATERIAL AND METHODS 11 2.1 Mice Cohorts 11 2.2 Cell Culture 11 2.3 Adenovirus Infection 12 2.4 RNA Isolation and Quantitative Real-Time PCR 12 2.5 Western Blot 14 2.6 Electrophoresis of Myosin Heavy Chain Isoforms 15 2.7 Muscle Force Measurements 15 2.8 Double-Labeled Immunofluorescence Assay 16 2.9 Immunohistochemistry from Paraffin-Embedded Sections 18 2.10 Enzymatic Histochemistry for Cytochrome C Oxidase (COX) Staining 18 2.11 Statistical Analysis 19 CHPATER 3 RESULTS 20 3.1 NRIP Locates at Sacromeric Z-disc and Colocalizes with Calcineurin. 20 3.2 Decreased Isometric Force in NRIP-/- Hindlimb Muscles. 21 3.3 Decreased Type I Slow Fibers and Mitochondria Oxidative Activity in NRIP Deficient Mice. 23 3.4 Loss of NRIP Leads to Decrease NFATc1 Activity and Type I Slow Fibers Expression in Mouse C2C12 Myoblasts. 26 3.5 Gender Effect of Muscle Performance in NRIP-/- Mice. 27 CHAPTER 4 DISCUSSION 29 REFERENCES 36 FIGURES 46 | |
dc.language.iso | en | |
dc.title | 探討NRIP在骨骼肌功能上的角色 | zh_TW |
dc.title | The Role of NRIP in Skeletal Muscle Functions | en |
dc.type | Thesis | |
dc.date.schoolyear | 100-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 符文美,游麗如,顏裕庭 | |
dc.subject.keyword | 核受體交互作用蛋白,骨骼肌,肌肉無力,鈣調磷酸酶,肌凝蛋白重鏈, | zh_TW |
dc.subject.keyword | NRIP,skeletal muscle,muscle fatigue,calcineurin,slow myosin, | en |
dc.relation.page | 56 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2012-08-09 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 微生物學研究所 | zh_TW |
顯示於系所單位: | 微生物學科所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-101-1.pdf 目前未授權公開取用 | 2.16 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。