為了解開心室發育的機制，人類心臟的基因體分析已經揭發了大規模的基因表現涉及在出生後心室發育過程裡。然而基因表現能否反應到功能的呈現，需要進一步檢視蛋白質表現來確定。本研究藉由合併定性新生鼠心室蛋白質圖譜和定量蛋白質體的分析，研究老鼠出生後心室發育的機制。
在第一個研究主題裡，我們透過合併次細胞蛋白質體策略，多樣化性萃取及一維逆相液相層析/電灑式/質譜/質譜建構一個高可信度含有258個蛋白質的新生鼠心室蛋白質圖譜。在嚴謹的評估次細胞分離及多樣化性萃取的效力下，我們推論從新生鼠心室鑑定出來的某些非預期的蛋白質次細胞分佈和特定蛋白質群組可能具有生理上的關聯性。
在第二個研究主題裡，藉由大規模深度的分析已建構的新生鼠心室蛋白質圖譜存在的生物路徑和網狀系統，幫助我們發現在新生鼠心室中前三名主要存在的生物機制依序是蛋白質合成，心臟能量使用和染色質的裝配與重組。再藉由進一步的半定量性西方墨點法分析，一個有趣的出生後心室發育機制被提出。
在最後的研究主題，我們採用相同蛋白質分離的策略合併雙甲基化穩定同位素標定法量化心室蛋白質在新生鼠和出生後四週鼠相對的蛋白質含量的改變，在67個量化的蛋白質中，主要有顯著蛋白質含量改變的是參與在粒線體內膜的氧化磷酸化的粒線體蛋白。相對應的，參與在粒線體動態的蛋白含量也呈現發育趨式的轉變。
藉由合併次細胞分離和非膠體型蛋白質體的策略允許我們建立一個新生鼠心室蛋白質體。在合併多種不同的方法(組織學，免疫組織學，免疫螢光和半定量西方墨點法分析)下，一個清楚的整體性蛋白質表現的改變(例如醣解酵素，收縮性蛋白，組蛋白亞型)被證實在出生後老鼠心室發育的過程中發生。藉由定量蛋白質體的分析證實發育過程中也涉及到特定蛋白質含量的改變(例如參與在粒線體氧化磷酸化反應的酵素) 我們的結果暗示發育過程中組蛋白亞型組成的轉變可能是一個埋置的機制趨動不同發育時期染色質重塑的轉換，可能因而造成心肌生長的方式由增殖轉化成肥大 合併早期在心臟粒線體的研究成果和在本研究有趣的發現，我們推論在新生鼠心室存在的相對活躍的粒線體動態可能和出生後擴展心肌組織中未成熟的網狀粒線體組織有關，隨後顯著的增加粒線體酵素含量在青春期前的老鼠心室可能和增強粒線體效力有關，由此反應因增加心臟收縮力而提高的心臟能量需求。

To unravel the mechanism for ventricular development, genomic analyses of human hearts have revealed a large scale of genes involved in postnatal development of hearts. However, the discovery of development-dependent gene expression requires further refinement at the protein level. The aim of this thesis is to investigate the biologic changes in heart development during postnatal period by dissecting qualitative proteomic map and quantitative proteomic analysis.
Our first objective was to construct a neonatal rat ventricular proteome by subcellular fractionation, extraction pre-fractionation, and 1-D-RPLC-ESI-MS spectrometry analysis. The modified subcellular proteomic analysis allowed us to reveal with 258 proteins with at least two peptides matched or single peptide assigments confirmed by immunofluorescence or Western blotting analysis. Extensive analyzses in the efficiency of subcellular fractionation and extraction prefractionation were evaluated. Based on the establishment of methodology, we infer some unpredicted subcellular location of identified proteins and specific cluster proteins identification revealed from neonatal rat ventricles may with physiologic relevant.
The second objective was to perform functional annotation after the ventricular proteome of neonatal rats was established. Extensive pathway and network analysis allowed for the discovery of the first three significant pathways in neonatal ventricles are protein synthesis, cardiac fuel usage and chromatin assembly and remodeling. After semi-quantitative Western blotting analysis of some identified proteins, a unique mechanism for postnatal development of neonatal ventricles was proposed.
The last objective was to combine the same strategy of protein separation with stable isotope dimethyl labeling to quantify the relative change of ventricular proteins in the membrane fractions from both neonatal and 4-week ventricles. Of 67 proteins quantified, the proteins with significant changes were related to mitochondrial respiratory chain. Correspondingly, the abundance of the proteins involved in mitochondrial dynamics was changed in a development-dependent manner.
In conclusion, the combination of subcellular fractionation with non-gel based proteomic analyses allowed us to establish a ventricular proteome of neonatal rats. Multiple biotechniques (histology, immunohistology, immunofluorescence and semi-quantitative Western blotting analysis) showed a development-dependent shift in protein composition (such as glycolytic enzymes, contractile proteins, and histone isoforms). Quantitative proteomic analyses demonstrated a development-dependent shift in protein abundance (such as enzymes involved in mitochondrial respiratory chain). Our data suggest that the shift in the composition of histone isoforms could be an embedded program which may be related to chromatin remodeling and influence the shift of cardiac growth from hyperplasia to hypertrophy. Combing ultrastructural observations of early studies in cardiac mitochondria with interesting findings in our study, an integrative drawing of cardiac mitochondria development after birth was depicted. We suppose relatively more active mitochondrial dynamics in neonatal rat ventricles may be involved in organization and/or expansion of immature mitochondrial reticulum, following significantly increased enzyme content of mitochondria in pre-pubertal ventricles correlates with increased mitochondrial capacity to response increased energy consumption via alternation of cardiac muscle contractility.

1.Adlakha, R.C., Sahasrabuddhe, C.G., Wright, D.A., Lindsey, W.F., Smith, M.L., and Rao, P.N. (1982). Chromosome-bound mitotic factors: release by endonucleases. Nucleic Acids Res 10, 4107-4117.
2.Agarkova, I., Auerbach, D., Ehler, E., and Perriard, J.-C. (2000). A Novel Marker for Vertebrate Embryonic Heart, the EH-myomesin Isoform. J. Biol. Chem. 275, 10256-10264.
3.Akazawa, H., and Komuro, I. (2003). Roles of Cardiac Transcription Factors in Cardiac Hypertrophy. Circ Res 92, 1079-1088.
4.Andres, A., Satrustegui, J., and Machado, A. (1984). Development of enzymes of energy metabolism in rat heart. Biol Neonate 45, 78-85.
5.Angelov, D., Bondarenko, V.A., Almagro, S., Menoni, H., Mongelard, F., Hans, F., Mietton, F., Studitsky, V.M., Hamiche, A., Dimitrov, S., and Bouvet, P. (2006). Nucleolin is a histone chaperone with FACT-like activity and assists remodeling of nucleosomes. EMBO J 25, 1669-1679.
6.Anversa, P., Leri, A., and Kajstura, J. (2006). Cardiac Regeneration. J Am Coll Cardiol 47, 1769-1776.
7.Arber, S., Halder, G., and Caroni, P. (1994). Muscle LIM protein, a novel essential regulator of myogenesis, promotes myogenic differentiation. Cell 79, 221-231.
8.Bartman, T., and Hove, J. (2005). Mechanics and function in heart morphogenesis. Dev Dyn 233, 373-381.
9.Bass, A., Stejskalova, M., Stieglerova, A., Ostadal, B., and Samanek, M. (2001). Ontogenetic development of energy-supplying enzymes in rat and guinea-pig heart. Physiol Res 50, 237-245.
10.Bassani, R.A., and Bassani, J.W.M. (2002). Contribution of Ca2+ transporters to relaxation in intact ventricular myocytes from developing rats. Am J Physiol Heart Circ Physiol 282, H2406-2413.
11.Bers, D.M. (2002). Cardiac excitation-contraction coupling. Nature 415, 198-205.
12.Boluyt, M.O., Brevick, J.L., Rogers, D.S., Randall, M.J., Scalia, A.F., and Li, Z.B. (2006). Changes in the rat heart proteome induced by exercise training: Increased abundance of heat shock protein hsp20. Proteomics 6, 3154-3169.
13.Borer, R.A., Lehner, C.F., Eppenberger, H.M., and Nigg, E.A. (1989). Major nucleolar proteins shuttle between nucleus and cytoplasm. Cell 56, 379-390.
14.Brandenburger, Y., Jenkins, A., Autelitano, D.J., and Hannan, R.D. (2001). Increased expression of UBF is a critical determinant for rRNA synthesis and hypertrophic growth of cardiac myocytes. FASEB J 15, 2051-2053.
15.Brown, N.F., Weis, B.C., Husti, J.E., Foster, D.W., and McGarry, J.D. (1995). Mitochondrial carnitine palmitoyltransferase I isoform switching in the developing rat heart. J Biol Chem 270, 8952-8957.
16.Cairns, B.R., Lorch, Y., Li, Y., Zhang, M., Lacomis, L., Erdjument-Bromage, H., Tempst, P., Du, J., Laurent, B., and Kornberg, R.D. (1996). RSC, an essential, abundant chromatin-remodeling complex. Cell 87, 1249-1260.
17.Carrier, L., Boheler, K.R., Chassagne, C., de la Bastie, D., Wisnewsky, C., Lakatta, E.G., and Schwartz, K. (1992). Expression of the sarcomeric actin isogenes in the rat heart with development and senescence. Circ Res 70, 999-1005.
18.Casey, T.M., Arthur, P.G., and Bogoyevitch, M.A. (2005). Proteomic Analysis Reveals Different Protein Changes during Endothelin-1- or Leukemic Inhibitory Factor-induced Hypertrophy of Cardiomyocytes in Vitro. Mol Cell Proteomics 4, 651-661.
19.Chen, H., and Chan, D.C. (2005). Emerging functions of mammalian mitochondrial fusion and fission. Hum Mol Genet 14 Spec No. 2, R283-289.
20.Cohen, N.M., and Lederer, W.J. (1988). Changes in the calcium current of rat heart ventricular myocytes during development. J Physiol 406, 115-146.
21.Daneshrad, Z., Verdys, M., Birot, O., Troff, F., Bigard, A.X., and Rossi, A. (2003). Chronic hypoxia delays myocardial lactate dehydrogenase maturation in young rats. Exp Physiol 88, 405-413.
22.Demange, P., Voges, D., Benz, J., Liemann, S., Gottig, P., Berendes, R., Burger, A., and Huber, R. (1994). Annexin V: the key to understanding ion selectivity and voltage regulation? Trends Biochem Sci 19, 272-276.
23.Deng, H., Sun, Y., Zhang, Y., Luo, X., Hou, W., Yan, L., Chen, Y., Tian, E., Han, J., and Zhang, H. (2007). Transcription factor NFY globally represses the expression of the C. elegans Hox gene Abdominal-B homolog egl-5. Dev Biol 308, 583-592.
24.Dorner, A., Olesch, M., Giessen, S., Pauschinger, M., and Schultheiss, H.P. (1999). Transcription of the adenine nucleotide translocase isoforms in various types of tissues in the rat. Biochim Biophys Acta 1417, 16-24.
25.Dowell, R.T., and Fu, M.C. (1998). Heterogeneous cellular expression of creatine kinase isoenzyme during normal rat heart development. Mol Cell Biochem 178, 87-94.
26.Drahota, Z., Milerova, M., Stieglerova, A., Houstek, J., and Ostadal, B. (2004). Developmental changes of cytochrome c oxidase and citrate synthase in rat heart homogenate. Physiol Res 53, 119-122.
27.Drahota, Z., Milerova, M., Stieglerova, A., Skarka, L., Houstek, J., and Ostadal, B. (2005). Development of cytochrome-c oxidase activity in rat heart: downregulation in newborn rats. Cell Biochem Biophys 43, 87-94.
28.Dreger, M. (2003). Proteome analysis at the level of subcellular structures. Eur J Biochem 270, 589-599.
29.Dreger, M., Bengtsson, L., Schoneberg, T., Otto, H., and Hucho, F. (2001). Nuclear envelope proteomics: novel integral membrane proteins of the inner nuclear membrane. Proc Natl Acad Sci U S A 98, 11943-11948.
30.Dunaway, G.A., Kasten, T.P., and Kolm, P. (1986). Alteration of 6-phosphofructo-1-kinase isozyme pools during heart development and aging. J Biol Chem 261, 17170-17173.
31.Eichhorn, E.J. (1998). Medical therapy of chronic heart failure. Role of ACE inhibitors and beta-blockers. Cardiol Clin 16, 711-725, ix.
32.Fan, G.C., Yuan, Q., and Kranias, E.G. (2008). Regulatory roles of junctin in sarcoplasmic reticulum calcium cycling and myocardial function. Trends Cardiovasc Med 18, 1-5.
33.Fazal, M.A., Palmer, V.R., and Dovichi, N.J. (2006). Analysis of differential detergent fractions of an AtT-20 cellular homogenate using one- and two-dimensional capillary electrophoresis. J Chromatogr A 1130, 182-189.
34.Fenn, J.B., Mann, M., Meng, C.K., Wong, S.F., and Whitehouse, C.M. (1989). Electrospray ionization for mass spectrometry of large biomolecules. Science 246, 64-71.
35.Field, M.L., Khan, O., Abbaraju, J., and Clark, J.F. (2006). Functional compartmentation of glycogen phosphorylase with creatine kinase and Ca2+ ATPase in skeletal muscle. J Theor Biol 238, 257-268.
36.Flucher, B.E., and Franzini-Armstrong, C. (1996). Formation of junctions involved in excitation-contraction coupling in skeletal and cardiac muscle. Proc Natl Acad Sci U S A 93, 8101-8106.
37.Forner, F., Foster, L.J., Campanaro, S., Valle, G., and Mann, M. (2006). Quantitative proteomic comparison of rat mitochondria from muscle, heart, and liver. Mol Cell Proteomics 5, 608-619.
38.Fujiki, Y., Hubbard, A.L., Fowler, S., and Lazarow, P.B. (1982). Isolation of intracellular membranes by means of sodium carbonate treatment: application to endoplasmic reticulum. J Cell Biol 93, 97-102.
39.Furukawa, K., Fritze, C.E., and Gerace, L. (1998). The major nuclear envelope targeting domain of LAP2 coincides with its lamin binding region but is distinct from its chromatin interaction domain. J Biol Chem 273, 4213-4219.
40.Futcher, B., Latter, G.I., Monardo, P., McLaughlin, C.S., and Garrels, J.I. (1999). A sampling of the yeast proteome. Mol Cell Biol 19, 7357-7368.
41.Gachet, Y., Tournier, S., Lee, M., Lazaris-Karatzas, A., Poulton, T., and Bommer, U.A. (1999). The growth-related, translationally controlled protein P23 has properties of a tubulin binding protein and associates transiently with microtubules during the cell cycle. J Cell Sci 112 ( Pt 8), 1257-1271.
42.Gambke, B., Lyons, G.E., Haselgrove, J., Kelly, A.M., and Rubinstein, N.A. (1983). Thyroidal and neural control of myosin transitions during development of rat fast and slow muscles. FEBS Lett 156, 335-339.
43.Gibbs, R.A., Weinstock, G.M., Metzker, M.L., Muzny, D.M., Sodergren, E.J., Scherer, S., Scott, G., Steffen, D., Worley, K.C., Burch, P.E. (2004). Genome sequence of the Brown Norway rat yields insights into mammalian evolution. Nature 428, 493-521.
44.Goffart, S., von Kleist-Retzow, J.C., and Wiesner, R.J. (2004). Regulation of mitochondrial proliferation in the heart: power-plant failure contributes to cardiac failure in hypertrophy. Cardiovasc Res 64, 198-207.
45.Gombosova, I., Boknik, P., Kirchhefer, U., Knapp, J., Luss, H., Muller, F.U., Muller, T., Vahlensieck, U., Schmitz, W., Bodor, G.S., and Neumann, J. (1998). Postnatal changes in contractile time parameters, calcium regulatory proteins, and phosphatases. Am J Physiol 274, H2123-2132.
46.Gomes, A.V., Venkatraman, G., Davis, J.P., Tikunova, S.B., Engel, P., Solaro, R.J., and Potter, J.D. (2004). Cardiac troponin T isoforms affect the Ca(2+) sensitivity of force development in the presence of slow skeletal troponin I: insights into the role of troponin T isoforms in the fetal heart. J Biol Chem 279, 49579-49587.
47.Goode, N., Hughes, K., Woodgett, J.R., and Parker, P.J. (1992). Differential regulation of glycogen synthase kinase-3 beta by protein kinase C isotypes. J Biol Chem 267, 16878-16882.
48.Gorg, A., Obermaier, C., Boguth, G., Harder, A., Scheibe, B., Wildgruber, R., and Weiss, W. (2000). The current state of two-dimensional electrophoresis with immobilized pH gradients. Electrophoresis 21, 1037-1053.
49.Gygi, S.P., Rochon, Y., Franza, B.R., and Aebersold, R. (1999). Correlation between protein and mRNA abundance in yeast. Mol Cell Biol 19, 1720-1730.
50.Haase, H., Alvarez, J., Petzhold, D., Doller, A., Behlke, J., Erdmann, J., Hetzer, R., Regitz-Zagrosek, V., Vassort, G., and Morano, I. (2005). Ahnak is critical for cardiac Ca(V)1.2 calcium channel function and its beta-adrenergic regulation. FASEB J 19, 1969-1977.
51.Hamid, S.A., Bower, H.S., and Baxter, G.F. (2007). Rho kinase activation plays a major role as a mediator of irreversible injury in reperfused myocardium. Am J Physiol Heart Circ Physiol 292, H2598-2606.
52.Harms, G., Kraft, R., Grelle, G., Volz, B., Dernedde, J., and Tauber, R. (2001). Identification of nucleolin as a new L-selectin ligand. Biochem. J. 360, 531-538.
53.Henry, K.D., Williams, E.R., Wang, B.H., McLafferty, F.W., Shabanowitz, J., and Hunt, D.F. (1989). Fourier-transform mass spectrometry of large molecules by electrospray ionization. Proc Natl Acad Sci U S A 86, 9075-9078.
54.Hirakow, R., Gotoh, T., and Watanabe, T. (1980). Quantitative studies on the ultrastructural differentiation and growth of mammalian cardiac muscle cells. I. The atria and ventricles of the rat. Acta Anat (Basel) 108, 144-152.
55.Ho, L., Wexler, I.D., Liu, T.C., Thekkumkara, T.J., and Patel, M.S. (1989). Characterization of cDNAs encoding human pyruvate dehydrogenase alpha subunit. Proc Natl Acad Sci U S A 86, 5330-5334.
56.Hoerter, J.A., Kuznetsov, A., and Ventura-Clapier, R. (1991). Functional development of the creatine kinase system in perinatal rabbit heart. Circ Res 69, 665-676.
57.Hoerter, J.A., Ventura-Clapier, R., and Kuznetsov, A. (1994). Compartmentation of creatine kinases during perinatal development of mammalian heart. Mol Cell Biochem 133-134, 277-286.
58.Hojlund, K., Yi, Z., Hwang, H., Bowen, B., Lefort, N., Flynn, C.R., Langlais, P., Weintraub, S.T., and Mandarino, L.J. (2008). Characterization of the human skeletal muscle proteome by one-dimensional gel electrophoresis and HPLC-ESI-MS/MS. Mol Cell Proteomics 7, 257-267.
59.Hong, S.J., Gokulrangan, G., and Schoneich, C. (2007). Proteomic analysis of age dependent nitration of rat cardiac proteins by solution isoelectric focusing coupled to nanoHPLC tandem mass spectrometry. Exp Gerontol 42, 639-651.
60.Hopkins, S.F., Jr., McCutcheon, E.P., and Wekstein, D.R. (1973). Postnatal changes in rat ventricular function. Circ Res 32, 685-691.
61.Hsu, J.L., Huang, S.Y., Chow, N.H., and Chen, S.H. (2003). Stable-isotope dimethyl labeling for quantitative proteomics. Anal Chem 75, 6843-6852.
62.Huang, S.Y., Tsai, M.L., Chen, G.Y., Wu, C.J., and Chen, S.H. (2007). A systematic MS-based approach for identifying in vitro substrates of PKA and PKG in rat uteri. J Proteome Res 6, 2674-2684.
63.Huang, S.Y., Tsai, M.L., Wu, C.J., Hsu, J.L., Ho, S.H., and Chen, S.H. (2006). Quantitation of protein phosphorylation in pregnant rat uteri using stable isotope dimethyl labeling coupled with IMAC. Proteomics 6, 1722-1734.
64.Huber, L.A., Pfaller, K., and Vietor, I. (2003). Organelle proteomics: implications for subcellular fractionation in proteomics. Circ Res 92, 962-968.
65.Huh, T.L., Casazza, J.P., Huh, J.W., Chi, Y.T., and Song, B.J. (1990). Characterization of two cDNA clones for pyruvate dehydrogenase E1 beta subunit and its regulation in tricarboxylic acid cycle-deficient fibroblast. J Biol Chem 265, 13320-13326.
66.Hummon, A.B., Lim, S.R., Difilippantonio, M.J., and Ried, T. (2007). Isolation and solubilization of proteins after TRIzol extraction of RNA and DNA from patient material following prolonged storage. Biotechniques 42, 467-470, 472.
67.Hwang, D.M., Dempsey, A.A., Lee, C.Y., and Liew, C.C. (2000). Identification of differentially expressed genes in cardiac hypertrophy by analysis of expressed sequence tags. Genomics 66, 1-14.
68.Ikenoya, M., Hidaka, H., Hosoya, T., Suzuki, M., Yamamoto, N., and Sasaki, Y. (2002). Inhibition of rho-kinase-induced myristoylated alanine-rich C kinase substrate (MARCKS) phosphorylation in human neuronal cells by H-1152, a novel and specific Rho-kinase inhibitor. J Neurochem 81, 9-16.
69.Imura, H., Caputo, M., Parry, A., Pawade, A., Angelini, G.D., and Suleiman, M.S. (2001). Age-dependent and hypoxia-related differences in myocardial protection during pediatric open heart surgery. Circulation 103, 1551-1556.
70.Ishihama, Y., Oda, Y., Tabata, T., Sato, T., Nagasu, T., Rappsilber, J., and Mann, M. (2005). Exponentially modified protein abundance index (emPAI) for estimation of absolute protein amount in proteomics by the number of sequenced peptides per protein. Mol Cell Proteomics 4, 1265-1272.
71.Iurkov Iu, A., Alatyrtsev, V.V., and Daikhin, E.I. (1975). Intracellular distribution of creatine kinase isoenzymes in the brains and hearts of rats at different stages of postnatal development. Ontogenez 6, 368-373.
72.Jansa, P., Burek, C., Sander, E.E., and Grummt, I. (2001). The transcript release factor PTRF augments ribosomal gene transcription by facilitating reinitiation of RNA polymerase I. Nucleic Acids Res 29, 423-429.
73.Jin, X., Xia, L., Wang, L.S., Shi, J.Z., Zheng, Y., Chen, W.L., Zhang, L., Liu, Z.G., Chen, G.Q., and Fang, N.Y. (2006). Differential protein expression in hypertrophic heart with and without hypertension in spontaneously hypertensive rats. Proteomics 6, 1948-1956.
74.Kanski, J., Behring, A., Pelling, J., and Schoneich, C. (2005). Proteomic identification of 3-nitrotyrosine-containing rat cardiac proteins: effects of biological aging. Am J Physiol Heart Circ Physiol 288, H371-381.
75.Karas, M., and Hillenkamp, F. (1988). Laser desorption ionization of proteins with molecular masses exceeding 10,000 daltons. Anal Chem 60, 2299-2301.
76.Keller, A., Rouzeau, J.D., Farhadian, F., Wisnewsky, C., Marotte, F., Lamande, N., Samuel, J.L., Schwartz, K., Lazar, M., and Lucas, M. (1995). Differential expression of alpha- and beta-enolase genes during rat heart development and hypertrophy. Am J Physiol 269, H1843-1851.
77.Kinugawa, K., Jeong, M.Y., Bristow, M.R., and Long, C.S. (2005). Thyroid hormone induces cardiac myocyte hypertrophy in a thyroid hormone receptor alpha1-specific manner that requires TAK1 and p38 mitogen-activated protein kinase. Mol Endocrinol 19, 1618-1628.
78.Kinyamu, H.K., Chen, J., and Archer, T.K. (2005). Linking the ubiquitin-proteasome pathway to chromatin remodeling/modification by nuclear receptors. J Mol Endocrinol 34, 281-297.
79.Koss, K.L., and Kranias, E.G. (1996). Phospholamban: a prominent regulator of myocardial contractility. Circ Res 79, 1059-1063.
80.Kuznetsov, A.V., Usson, Y., Leverve, X., and Margreiter, R. (2004). Subcellular heterogeneity of mitochondrial function and dysfunction: evidence obtained by confocal imaging. Mol Cell Biochem 256-257, 359-365.
81.Lam, L., Arthur, J., and Semsarian, C. (2007). Proteome map of the normal murine ventricular myocardium. Proteomics 7, 3629-3633.
82.Lavrentyev, E.N., He, D., and Cook, G.A. (2004). Expression of genes participating in regulation of fatty acid and glucose utilization and energy metabolism in developing rat hearts. Am J Physiol Heart Circ Physiol 287, H2035-2042.
83.Lee, W.C., and Lee, K.H. (2004). Applications of affinity chromatography in proteomics. Anal Biochem 324, 1-10.
84.Lemos, T.A., Passos, D.O., Nery, F.C., and Kobarg, J. (2003). Characterization of a new family of proteins that interact with the C-terminal region of the chromatin-remodeling factor CHD-3. FEBS Lett 533, 14-20.
85.Li, F., Wang, X., Capasso, J.M., and Gerdes, A.M. (1996). Rapid transition of cardiac myocytes from hyperplasia to hypertrophy during postnatal development. J Mol Cell Cardiol 28, 1737-1746.
86.Li, X.P., Pleissner, K.P., Scheler, C., Regitz-Zagrosek, V., Salnikow, J., and Jungblut, P.R. (1999). A two-dimensional electrophoresis database of rat heart proteins. Electrophoresis 20, 891-897.
87.Li, Z.B., Flint, P.W., and Boluyt, M.O. (2005). Evaluation of several two-dimensional gel electrophoresis techniques in cardiac proteomics. Electrophoresis 26, 3572-3585.
88.Lompre, A.M., Nadal-Ginard, B., and Mahdavi, V. (1984). Expression of the cardiac ventricular alpha- and beta-myosin heavy chain genes is developmentally and hormonally regulated. J. Biol. Chem. 259, 6437-6446.
89.Madeo, F., Schlauer, J., Zischka, H., Mecke, D., and Frohlich, K.-U. (1998). Tyrosine Phosphorylation Regulates Cell Cycle-dependent Nuclear Localization of Cdc48p. Mol. Biol. Cell 9, 131-141.
90.McGregor, E., and Dunn, M.J. (2006). Proteomics of the heart: unraveling disease. Circ Res 98, 309-321.
91.Mesaeli, N., Nakamura, K., Zvaritch, E., Dickie, P., Dziak, E., Krause, K.H., Opas, M., MacLennan, D.H., and Michalak, M. (1999). Calreticulin is essential for cardiac development. J Cell Biol 144, 857-868.
92.Metzger, J.M., Michele, D.E., Rust, E.M., Borton, A.R., and Westfall, M.V. (2003). Sarcomere thin filament regulatory isoforms. Evidence of a dominant effect of slow skeletal troponin I on cardiac contraction. J Biol Chem 278, 13118-13123.
93.Mishra, S., Saleh, A., Espino, P.S., Davie, J.R., and Murphy, L.J. (2006). Phosphorylation of histones by tissue transglutaminase. J Biol Chem 281, 5532-5538.
94.Molloy, M.P., Herbert, B.R., Walsh, B.J., Tyler, M.I., Traini, M., Sanchez, J.C., Hochstrasser, D.F., Williams, K.L., and Gooley, A.A. (1998). Extraction of membrane proteins by differential solubilization for separation using two-dimensional gel electrophoresis. Electrophoresis 19, 837-844.
95.Muth, E., Driscoll, W.J., Smalstig, A., Goping, G., and Mueller, G.P. (2004). Proteomic analysis of rat atrial secretory granules: a platform for testable hypotheses. Biochim Biophys Acta 1699, 263-275.
96.Negi, S.S., and Olson, M.O. (2006). Effects of interphase and mitotic phosphorylation on the mobility and location of nucleolar protein B23. J Cell Sci 119, 3676-3685.
97.Negretti, N., O'Neill, S.C., and Eisner, D.A. (1993). The relative contributions of different intracellular and sarcolemmal systems to relaxation in rat ventricular myocytes. Cardiovasc Res 27, 1826-1830.
98.Nicol, R.L., Frey, N., Pearson, G., Cobb, M., Richardson, J., and Olson, E.N. (2001). Activated MEK5 induces serial assembly of sarcomeres and eccentric cardiac hypertrophy. EMBO J 20, 2757-2767.
99.O'Farrell, P.H. (1975). High resolution two-dimensional electrophoresis of proteins. J Biol Chem 250, 4007-4021.
100.Olivetti, G., Anversa, P., and Loud, A.V. (1980). Morphometric study of early postnatal development in the left and right ventricular myocardium of the rat. II. Tissue composition, capillary growth, and sarcoplasmic alterations. Circ Res 46, 503-512.
101.Ookata, K., Hisanaga, S., Bulinski, J.C., Murofushi, H., Aizawa, H., Itoh, T.J., Hotani, H., Okumura, E., Tachibana, K., and Kishimoto, T. (1995). Cyclin B interaction with microtubule-associated protein 4 (MAP4) targets p34cdc2 kinase to microtubules and is a potential regulator of M-phase microtubule dynamics. J Cell Biol 128, 849-862.
102.Opitz, C.A., Leake, M.C., Makarenko, I., Benes, V., and Linke, W.A. (2004). Developmentally Regulated Switching of Titin Size Alters Myofibrillar Stiffness in the Perinatal Heart. Circ Res 94, 967-975.
103.Osterman, J., Fritz, P.J., and Wuntch, T. (1973). Pyruvate kinase isozymes from rat tissues. Developmental studies. J Biol Chem 248, 1011-1018.
104.Palmer, J.W., Tandler, B., and Hoppel, C.L. (1977). Biochemical properties of subsarcolemmal and interfibrillar mitochondria isolated from rat cardiac muscle. J Biol Chem 252, 8731-8739.
105.Paranjape, S.M., Krumm, A., and Kadonaga, J.T. (1995). HMG17 is a chromatin-specific transcriptional coactivator that increases the efficiency of transcription initiation. Genes Dev 9, 1978-1991.
106.Pedersen, S.K., Harry, J.L., Sebastian, L., Baker, J., Traini, M.D., McCarthy, J.T., Manoharan, A., Wilkins, M.R., Gooley, A.A., Righetti, P.G.. (2003). Unseen proteome: mining below the tip of the iceberg to find low abundance and membrane proteins. J Proteome Res 2, 303-311.
107.Ping, P., Zhang, J., Pierce, W.M., Jr., and Bolli, R. (2001). Functional proteomic analysis of protein kinase C epsilon signaling complexes in the normal heart and during cardioprotection. Circ Res 88, 59-62.
108.Portman, M.A., Chen, S.H., Xiao, Y., and Ning, X.H. (1999). Maturational changes in gene expression for adenine nucleotide translocator isoforms and betaF1-ATPase in rabbit heart. Mol Genet Metab 66, 75-79.
109.Rabilloud, T. (2002). Two-dimensional gel electrophoresis in proteomics: old, old fashioned, but it still climbs up the mountains. Proteomics 2, 3-10.
110.Rajabi, M., Kassiotis, C., Razeghi, P., and Taegtmeyer, H. (2007). Return to the fetal gene program protects the stressed heart: a strong hypothesis. Heart Fail Rev 12, 331-343.
111.Reinders, J., Lewandrowski, U., Moebius, J., Wagner, Y., and Sickmann, A. (2004). Challenges in mass spectrometry-based proteomics. Proteomics 4, 3686-3703.
112.Reynolds, K.J., Yao, X., and Fenselau, C. (2002). Proteolytic 18O labeling for comparative proteomics: evaluation of endoprotease Glu-C as the catalytic agent. J Proteome Res 1, 27-33.
113.Samarel, A.M. (1989). Regional differences in the in vivo synthesis and degradation of myosin subunits in rabbit ventricular myocardium. Circ Res 64, 193-202.
114.Santoni, V., Molloy, M., and Rabilloud, T. (2000). Membrane proteins and proteomics: un amour impossible? Electrophoresis 21, 1054-1070.
115.Schagger, H., Noack, H., Halangk, W., Brandt, U., and von Jagow, G. (1995). Cytochrome-c oxidase in developing rat heart. Enzymic properties and amino-terminal sequences suggest identity of the fetal heart and the adult liver isoform. Eur J Biochem 230, 235-241.
116.Schmidt-Zachmann, M.S., Dargemont, C., Kuhn, L.C., and Nigg, E.A. (1993). Nuclear export of proteins: the role of nuclear retention. Cell 74, 493-504.
117.Schonfeld, P., Schild, L., and Bohnensack, R. (1996). Expression of the ADP/ATP carrier and expansion of the mitochondrial (ATP + ADP) pool contribute to postnatal maturation of the rat heart. Eur J Biochem 241, 895-900.
118.Schott, P., Singer, S.S., Kogler, H., Neddermeier, D., Leineweber, K., Brodde, O.E., Regitz-Zagrosek, V., Schmidt, B., Dihazi, H., and Hasenfuss, G. (2005). Pressure overload and neurohumoral activation differentially affect the myocardial proteome. Proteomics 5, 1372-1381.
119.Sharp, P.M., and Li, W.H. (1987). The codon Adaptation Index--a measure of directional synonymous codon usage bias, and its potential applications. Nucleic Acids Res 15, 1281-1295.
120.Shen, X., and Masters, P.S. (2001). Evaluation of the role of heterogeneous nuclear ribonucleoprotein A1 as a host factor in murine coronavirus discontinuous transcription and genome replication. Proceedings of the National Academy of Sciences of the United States of America 98, 2717-2722.
121.Shi, S.T., Yu, G.-Y., and Lai, M.M.C. (2003). Multiple Type A/B Heterogeneous Nuclear Ribonucleoproteins (hnRNPs) Can Replace hnRNP A1 in Mouse Hepatitis Virus RNA Synthesis. J. Virol. 77, 10584-10593.
122.Skarka, L., Bardova, K., Brauner, P., Flachs, P., Jarkovska, D., Kopecky, J., and Ostadal, B. (2003). Expression of mitochondrial uncoupling protein 3 and adenine nucleotide translocase 1 genes in developing rat heart: putative involvement in control of mitochondrial membrane potential. J Mol Cell Cardiol 35, 321-330.
123.Smolka, M.B., Zhou, H., Purkayastha, S., and Aebersold, R. (2001). Optimization of the isotope-coded affinity tag-labeling procedure for quantitative proteome analysis. Anal Biochem 297, 25-31.
124.Srivastava, M., and Pollard, H.B. (1999). Molecular dissection of nucleolin's role in growth and cell proliferation: new insights. FASEB J 13, 1911-1922.
125.Stepien, G., Torroni, A., Chung, A.B., Hodge, J.A., and Wallace, D.C. (1992). Differential expression of adenine nucleotide translocator isoforms in mammalian tissues and during muscle cell differentiation. J Biol Chem 267, 14592-14597.
126.Stevens, R.J., Nishio, M.L., and Hood, D.A. (1995). Effect of hypothyroidism on the expression of cytochrome c and cytochrome c oxidase in heart and muscle during development. Mol Cell Biochem 143, 119-127.
127.Tagnaouti, N., Loebrich, S., Heisler, F., Pechmann, Y., Fehr, S., De Arcangelis, A., Georges-Labouesse, E., Adams, J.C., and Kneussel, M. (2007). Neuronal expression of muskelin in the rodent central nervous system. BMC Neurosci 8, 28.
128.Thrasher, J.R., Cooper, M.D., and Dunaway, G.A. (1981). Developmental changes in heart and muscle phosphofructokinase isozymes. J Biol Chem 256, 7844-7848.
129.Tiivel, T., Kadaya, L., Kuznetsov, A., Kaambre, T., Peet, N., Sikk, P., Braun, U., Ventura-Clapier, R., Saks, V., and Seppet, E.K. (2000). Developmental changes in regulation of mitochondrial respiration by ADP and creatine in rat heart in vivo. Mol Cell Biochem 208, 119-128.
130.Tillman, J.E., Yuan, J., Gu, G., Fazli, L., Ghosh, R., Flynt, A.S., Gleave, M., Rennie, P.S., and Kasper, S. (2007). DJ-1 Binds Androgen Receptor Directly and Mediates Its Activity in Hormonally Treated Prostate Cancer Cells. Cancer Res 67, 4630-4637.
131.Twig, G., Elorza, A., Molina, A.J., Mohamed, H., Wikstrom, J.D., Walzer, G., Stiles, L., Haigh, S.E., Katz, S., Las, G., et al. (2008). Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. EMBO J 27, 433-446.
132.Uhlen, M., and Ponten, F. (2005). Antibody-based proteomics for human tissue profiling. Mol Cell Proteomics 4, 384-393.
133.Vitorica, J., Cano, J., Satrustegui, J., and Machado, A. (1981). Comparison between developmental and senescent changes in enzyme activities linked to energy metabolism in rat heart. Mech Ageing Dev 16, 105-116.
134.Watkins, J., Basu, S., and Bogenhagen, D.F. (2008). A quantitative proteomic analysis of mitochondrial participation in p19 cell neuronal differentiation. J Proteome Res 7, 328-338.
135.Webb, S., Brown, N.A., and Anderson, R.H. (1998). Formation of the atrioventricular septal structures in the normal mouse. Circ Res 82, 645-656.
136.Wegrzyn, R.D., Hofmann, D., Merz, F., Nikolay, R., Rauch, T., Graf, C., and Deuerling, E. (2006). A conserved motif is prerequisite for the interaction of NAC with ribosomal protein L23 and nascent chains. J Biol Chem 281, 2847-2857.
137.Weis, B.C., Esser, V., Foster, D.W., and McGarry, J.D. (1994). Rat heart expresses two forms of mitochondrial carnitine palmitoyltransferase I. The minor component is identical to the liver enzyme. J Biol Chem 269, 18712-18715.
138.Westbrook, J.A., Yan, J.X., Wait, R., Welson, S.Y., and Dunn, M.J. (2001). Zooming-in on the proteome: very narrow-range immobilised pH gradients reveal more protein species and isoforms. Electrophoresis 22, 2865-2871.
139.Whalen, R.G., and Sell, S.M. (1980). Myosin from fetal hearts contains the skeletal muscle embryonic light chain. Nature 286, 731-733.
140.Wu, C.C., MacCoss, M.J., Howell, K.E., Matthews, D.E., and Yates, J.R., 3rd (2004). Metabolic labeling of mammalian organisms with stable isotopes for quantitative proteomic analysis. Anal Chem 76, 4951-4959.
141.Wu, G., Culley, D.E., and Zhang, W. (2005). Predicted highly expressed genes in the genomes of Streptomyces coelicolor and Streptomyces avermitilis and the implications for their metabolism. Microbiology 151, 2175-2187.
142.Yan, X., Schuldt, A.J., Price, R.L., Amende, I., Liu, F.F., Okoshi, K., Ho, K.K., Pope, A.J., Borg, T.K., Lorell, B.H., and Morgan, J.P. (2008). Pressure overload-induced hypertrophy in transgenic mice selectively overexpressing AT2 receptors in ventricular myocytes. Am J Physiol Heart Circ Physiol 294, H1274-1281.
143.Yen, H.-C.S., Espiritu, C., and Chang, E.C. (2003). Rpn5 Is a Conserved Proteasome Subunit and Required for Proper Proteasome Localization and Assembly. J. Biol. Chem. 278, 30669-30676.
144.Zeit-Har, S.A., and Drahota, Z. (1975). The development of mitochondrial oxidative enzymes in rat heart muscle. Physiol Bohemoslov 24, 289-296.