抑制環狀核苷酸磷酸二酯酶 3 (PDE3)對 3T3-L1 脂肪細胞內蛋白質表現之影響

以作者查詢圖書館館藏

、以作者查詢臺灣博碩士

、以作者查詢全國書目

、勘誤回報

、線上人數：85

、訪客IP：18.222.9.171

姓名

王柏翔(Bo-xiang Wang) 查詢紙本館藏

畢業系所

生命科學系

論文名稱

抑制環狀核苷酸磷酸二酯酶 3 (PDE3)對 3T3-L1 脂肪細胞內蛋白質表現之影響
(Effects of phosphodiesterase 3 (PDE3) inhibition on protein expression in 3T3-L1 adipocytes)

相關論文

★ PDE抑制劑與cAMP訊號傳導對類風濕性關節炎小鼠模型中CD4+ T細胞釋放IFN-g與IL-17A之調控	★ PDE4和cAMP訊號傳導於小鼠骨髓細胞分化為樹突細胞之角色
★ 利用斑馬魚研究肝臟疾病和肝癌之發生：B型肝炎病毒X抗原，黃麴毒素，p53突變，src和edn1的致癌作用及其協同效應	★ 環狀核苷酸磷酸二酯酶4對LPS/TLR4訊息傳導誘導小鼠巨噬細胞表現IFN-β的影響
★ 環狀核苷酸磷酸二酯酶4B對小鼠樹突細胞分化與CXCR4表現之調控	★ 利用聚乙烯亞胺輸送環狀核苷酸磷酸二酯酶4B之專一性反義寡核苷酸可抑制LPS刺激小鼠巨噬細胞釋放TNF-α
★ PDE4與PDE3抑制劑對膠原蛋白誘發DBA/1小鼠關節炎及釋放發炎激素IFN-γ與IL-17A的協同調控作用	★ 環狀核苷酸磷酸二酯酶4B對內毒素誘導巨噬細胞產生IL-1Ra和樹突細胞表現TLRs之影響及其對乾癬症生成之潛在角色
★ 環狀核苷酸磷酸二脂酶4B對內毒素刺激小鼠樹突細胞表現NOD1與CXCR4的影響	★ TDAG8 participates in different phases of neuropathic pain by regulating distinct pathways of substance P
★ Innovative Mind-Body Intervention Day Easy Exercise Increases Peripheral Blood CD34+ Cells and Attenuates Back Pain in Adults	★ Viscolin對不同免疫細胞發炎反應的影響
★ 環狀腺苷單磷酸與其它訊息傳遞因子對脂肪細胞釋放阻抗素之影響	★ 環狀核苷酸磷酸二酯酶4B對於小鼠T細胞功能之調節
★ 巨噬細胞中抑制PDE4對LPS誘導發炎反應之調控	★ 環狀核苷酸磷酸二酯酶4對LPS刺激小鼠巨噬細胞產生IL-1Ra之影響

檔案

[Endnote RIS 格式]

[Bibtex 格式]

[相關文章]

[文章引用]

[完整記錄]

[館藏目錄]

至系統瀏覽論文 ( 永不開放)

摘要(中)

環狀核苷酸磷酸二酯酶3 (phosphodiesterase 3；PDE3)在脂肪細胞中扮演重要的角色，藉由水解cAMP降低細胞內cAMP濃度可調節脂肪分解、脂肪生成與葡萄糖攝取等作用以維持細胞內能量平衡。已知增加脂肪細胞內cAMP的濃度會促進脂肪分解，相反的，降低cAMP則會阻礙脂肪分解並增加脂肪合成作用，然而在PDE3影響下會參與調控脂肪生成或代謝的蛋白質仍不甚清楚。本研究利用二維電泳與質譜技術分析鑑定脂肪細胞中受到PDE3調控的蛋白質。我們首先以PDE3抑制劑cilostazol與胰島素共同處理3T3-L1脂肪細胞18小時，之後萃取細胞內蛋白質並使用二維電泳分離，其膠體經銀染後顯示，有三個蛋白質表現強度上升，此電泳的果與胰島素單獨處理細胞之二維電泳分析結果比較顯示，有兩個蛋白質表現的上升是受到cilostazol調控所致。接著由質譜技術與胺基酸序列比對分析後，此兩個蛋白質身分為annexin a2 (ANX A2)與nucleoside diphosphate kinase b (NDPK-B)，第三個蛋白質點無法被質譜方法鑑定出。我們進一步以real-time PCR分析兩個蛋白質的mRNA表現，在胰島素存在下，cilostazol也會促使其基因的表現上升。另外，我們也使用β-adrenergic receptor的刺激劑isoproterenol (ISO)與cilostazol共同處理脂肪細胞8小時，二維電泳與質譜分析結果顯示thioredoxin-1 (TXN-1)的表現呈明顯上升，相同的，在ISO存在下，cilostazol對TXN-1 mRNA表現也有一致的提升。根據文獻報導，TXN-1與NDPK-B均有抑制脂肪生成的作用，由此我們推測，cilostazol抑制脂肪生成可能是經由促進此二蛋白質表現所致。此外，ANX A2在細胞內可能與CLUT4運送有關，因此我們推測在胰島素刺激下，cilostazol促進ANX A2的表現可能會增加GLUT4的運送，但此作用仍有待進一步實驗證明。

摘要(英)

Cyclic nucleotide phosphodiesterase 3B (PDE3B), a PDE3 family isozyme that hydrolyzes cAMP with high affinity, plays an important role in the regulation of energy homeostasis in adipocytes mainly through regulation of lipolysis, lipogenesis, gluconeogenesis, and glucose uptake. It is known that increasing intracellular cAMP concentration by inhibition of PDE3B triggers rapid lipid degradation, whereas decreasing cAMP level leads to antilipolytic action and lipogenesis. However, the proteins that are regulated by PDE3B in these lipid metabolic processes remain largely undefined. In this study, we used two-dimensional (2-D) gel electrophoresis and mass spectrometry to identify the proteins expressed in mouse 3T3-L1 adipocytes in the presence of the PDE3 inhibitor cilostazol. The initial results showed that three proteins were upregulated in 3T3-L1 cells after treatment with cilostazol and insulin for 18 h. Comparing to the 2-D gel results derived from the cells treated with insulin alone indicates that two of the three proteins were induced in expression by cilostazol. Following the mass spectrometry analysis, these proteins were identified as annexin a2 (ANX A2) and nucleoside diphosphate kinase b (NDPK-B). The third protein upregulated in the presence of cilostazol and insulin was not identified by the method. Further analysis by real-time PCR revealed that ANX A2 and NDPK-B mRNA expression was also upregulated by cilostazol. In a separate experimental setting, 3T3-L1 adipocytes were treated with cilostazol and the β-adrenergic receptor agonist isoproterenol (ISO) for 8 h, followed by 2-D gel analysis. The results showed that in the presence of ISO one protein was upregulated by cilostazol, and mass spectrometry identified it as thioredoxin-1 (TXN-1). This induction in TXN-1 protein also was associated with an increase in mRNA expression. Both TXN-1 and NDPK-B have been shown to inhibit lipogenesis in adipocytes. Thus, we rationalize that inhibition of PDE3B to induce TXN-1 and NDPK-B expression is a mechanism underlying the blockage of lipogenesis by cilostezol. In addition, ANX A2 is implicated in GLUT4 translocation in adipocytes, pointing to a potential role of PDE3 inhibitors in regulation of glucose transport via enhancing ANX A2 expression. This proposed effect, however, awaits further experimental attestation.

關鍵字(中)

★ 環狀核苷酸磷酸二酯酶 3
★ 脂肪細胞
★ 蛋白質

關鍵字(英)

★ phosphodiesterase 3
★ 3T3-L1
★ adipocytes
★ protein

論文目次

中文摘要 i
英文摘要 ii
誌謝 iv
目錄 v
圖目錄 viii
縮寫檢索表 ix
第一章緒論 1
1-1 脂肪組織(adipose tissue) 1
1-2 環狀腺苷單磷酸(3′,5′-cyclic adenosine monophosphate, cAMP)和脂肪代謝 1
1-3 環狀核苷酸磷酸雙酯酶(cyclic nucleotide phosphodiesterase, PDE) 2
1-4 PDE3 家族 4
1-5 PDE3B與脂肪細胞 5
1-6 PDE3抑制劑與脂肪代謝 7
1-7 脂肪細胞的蛋白質體學研究 7
1-8 Mass spectrometry的應用 8
第二章研究動機與目的 10
第三章實驗材料與方法 11
3-1 3T3-L1細胞株 11
3-2 實驗材料與儀器 11
3-2-1 3T3-L1細胞培養基 11
3-2-2 化學藥劑 11
3-2-3 實驗器材 12
3-3 實驗方法 13
3-3-1 細胞培養 13
3-3-2 細胞分化 13
3-3-3 脂肪細胞處理 13
3-4 細胞蛋白質製備 14
3-4-1 蛋白質萃取 14
3-4-2 蛋白質沉澱 14
3-4-3 蛋白質濃度檢測 15
3-5 蛋白質膠體電泳(SDS-polyacrylamide gel electrophoresis ; SDS-PAGE) 15
3-5-1 聚丙烯醯胺膠體(SDS-polyacrylamide gel)建製 15
3-5-2 SDS-PAGE電泳分析 16
3-5-3 孔雀藍(Coomassie blue R-250)染色 16
3-6 蛋白質二維電泳分析 16
3-6-1 等電點膠條聚焦作用(Isoelectric focusing) 16
3-6-2 等電聚焦的平衡作用 16
3-6-3 二維膠體電泳(2D gel electrophoresis) 17
3-6-4 硝酸銀染色 17
3-6-5 電泳膠體軟體分析 18
3-6-6 膠內蛋白質水解(In-gel digestion)與萃取 18
3-7 質譜儀分析 19
3-8 即時聚合酶鏈鎖反應(Real-time polymerase chain reaction) 19
3-8-1 脂肪細胞RNA之萃取 19
3-8-2 反轉錄作用 19
3-8-3 cDNA cleaning 20
3-8-4 即時聚合酵素連鎖反應 20
3-8-5 統計分析 21
第四章實驗結果 22
4-1 PDE3抑制劑cilostazol對脂肪細胞內蛋白質表現的影響 22
4-1-1 胰島素與cilostazol對蛋白質表現的影響 22
4-1-2 Isoproterenol (ISO)與cilostazol對蛋白質表現的影響 23
4-2 質譜儀分析蛋白質序列 24
4-3 Cilostazol與胰島素對ANX A2、NDPKB、SOD1 mRNA表現的影響 24
4-4 Isoproterenol (ISO)與ciostazol對TXN-1 mRNA表現的影響 26
第五章討論 28
第六章圖與圖解 34
參考文獻 49
附圖 58

參考文獻

Ahmad, F., L.N. Cong, L. Stenson Holst, L.M. Wang, T. Rahn Landstrom, J.H. Pierce, M.J. Quon, E. Degerman, and V.C. Manganiello. 2000. Cyclic nucleotide phosphodiesterase 3B is a downstream target of protein kinase B and may be involved in regulation of effects of protein kinase B on thymidine incorporation in FDCP2 cells. Journal of immunology. 164:4678-4688.
Al Qadi-Nassar, B., F. Bichon-Laurent, K. Portet, P. Tramini, B. Arnoux, and A. Michel. 2007. Effects of L-arginine and phosphodiesterase-5 inhibitor, sildenafil, on inflammation and airway responsiveness of sensitized BP2 mice. Fundamental & clinical pharmacology. 21:611-620.
Anciaux, K., K. Van Dommelen, R. Willems, D. Roymans, and H. Slegers. 1997. Inhibition of nucleoside diphosphate kinase (NDPK/nm23) by cAMP analogues. FEBS letters. 400:75-79.
Arnaud-Dabernat, S., K. Masse, M. Smani, E. Peuchant, M. Landry, P.M. Bourbon, R. Le Floch, J.Y. Daniel, and M. Larou. 2004. Nm23-M2/NDP kinase B induces endogenous c-myc and nm23-M1/NDP kinase A overexpression in BAF3 cells. Both NDP kinases protect the cells from oxidative stress-induced death. Experimental cell research. 301:293-304.
Arner, E.S., and A. Holmgren. 2000. Physiological functions of thioredoxin and thioredoxin reductase. European journal of biochemistry / FEBS. 267:6102-6109.
Ballart, X., M. Siches, J. Peinado-Onsurbe, D. Lopez-Tejero, M. Llobera, I. Ramirez, and M.Q. Robert. 2003. Isoproterenol increases active lipoprotein lipase in adipocyte medium and in rat plasma. Biochimie. 85:971-982.
Boden, G. 2008. Obesity and free fatty acids. Endocrinology and metabolism clinics of North America. 37:635-646, viii-ix.
Boissan, M., S. Dabernat, E. Peuchant, U. Schlattner, I. Lascu, and M.L. Lacombe. 2009. The mammalian Nm23/NDPK family: from metastasis control to cilia movement. Molecular and cellular biochemistry. 329:51-62.
Boswell-Smith, V., D. Spina, and C.P. Page. 2006. Phosphodiesterase inhibitors. British journal of pharmacology. 147 Suppl 1:S252-257.
Brasaemle, D.L., D.M. Levin, D.C. Adler-Wailes, and C. Londos. 2000. The lipolytic stimulation of 3T3-L1 adipocytes promotes the translocation of hormone-sensitive lipase to the surfaces of lipid storage droplets. Biochimica et biophysica acta. 1483:251-262.
Cai, X., S. Srivastava, S. Surindran, Z. Li, and E.Y. Skolnik. 2014. Regulation of the epithelial Ca(2)(+) channel TRPV5 by reversible histidine phosphorylation mediated by NDPK-B and PHPT1. Molecular biology of the cell. 25:1244-1250.
Choi, K.L., Y. Wang, C.A. Tse, K.S. Lam, G.J. Cooper, and A. Xu. 2004. Proteomic analysis of adipocyte differentiation: Evidence that alpha2 macroglobulin is involved in the adipose conversion of 3T3 L1 preadipocytes. Proteomics. 4:1840-1848.
Choi, Y.H., S. Park, S. Hockman, E. Zmuda-Trzebiatowska, F. Svennelid, M. Haluzik, O. Gavrilova, F. Ahmad, L. Pepin, M. Napolitano, M. Taira, F. Sundler, L. Stenson Holst, E. Degerman, and V.C. Manganiello. 2006. Alterations in regulation of energy homeostasis in cyclic nucleotide phosphodiesterase 3B-null mice. The Journal of clinical investigation. 116:3240-3251.
Chutkow, W.A., and R.T. Lee. 2011. Thioredoxin regulates adipogenesis through thioredoxin-interacting protein (Txnip) protein stability. The Journal of biological chemistry. 286:29139-29145.
Cong, L., K. Chen, J. Li, P. Gao, Q. Li, S. Mi, X. Wu, and A.Z. Zhao. 2007. Regulation of adiponectin and leptin secretion and expression by insulin through a PI3K-PDE3B dependent mechanism in rat primary adipocytes. The Biochemical journal. 403:519-525.
Conti, M., and J. Beavo. 2007. Biochemistry and physiology of cyclic nucleotide phosphodiesterases: essential components in cyclic nucleotide signaling. Annual review of biochemistry. 76:481-511.
Conti, M., W. Richter, C. Mehats, G. Livera, J.Y. Park, and C. Jin. 2003. Cyclic AMP-specific PDE4 phosphodiesterases as critical components of cyclic AMP signaling. The Journal of biological chemistry. 278:5493-5496.
Dawson, D.L., B.S. Cutler, M.H. Meissner, and D.E. Strandness. 1998. Cilostazol Has Beneficial Effects in Treatment of Intermittent Claudication : Results From a Multicenter, Randomized, Prospective, Double-blind Trial. Circulation. 98:678-686.
Degerman, E., F. Ahmad, Y.W. Chung, E. Guirguis, B. Omar, L. Stenson, and V. Manganiello. 2011. From PDE3B to the regulation of energy homeostasis. Current opinion in pharmacology. 11:676-682.
Degerman, E., C.J. Smith, H. Tornqvist, V. Vasta, P. Belfrage, and V.C. Manganiello. 1990. Evidence that insulin and isoprenaline activate the cGMP-inhibited low-Km cAMP phosphodiesterase in rat fat cells by phosphorylation. Proceedings of the National Academy of Sciences of the United States of America. 87:533-537.
Desvignes, T., P. Pontarotti, C. Fauvel, and J. Bobe. 2009. Nme protein family evolutionary history, a vertebrate perspective. BMC evolutionary biology. 9:256.
Dylla, S.J., J.P. Williams, J. Williford, and R.W. Hardy. 2000. Phosphatase activity in rat adipocytes: effects of insulin and insulin resistance. Journal of cellular biochemistry. 77:445-454.
Elks, M.L., and V.C. Manganiello. 1985. Antilipolytic action of insulin: role of cAMP phosphodiesterase activation. Endocrinology. 116:2119-2121.
Eriksson, J.W., C. Wesslau, and U. Smith. 1994. The cGMP-inhibitable phosphodiesterase modulates glucose transport activation by insulin. Biochimica et biophysica acta. 1189:163-167.
Fenn, J.B., M. Mann, C.K. Meng, S.F. Wong, and C.M. Whitehouse. 1989. Electrospray ionization for mass spectrometry of large biomolecules. Science. 246:64-71.
Francis, S.H., I.V. Turko, and J.D. Corbin. 2001. Cyclic nucleotide phosphodiesterases: relating structure and function. Progress in nucleic acid research and molecular biology. 65:1-52.
Frank, S., K. Zacharowski, G.M. Wray, C. Thiemermann, and J. Pfeilschifter. 1999. Identification of copper/zinc superoxide dismutase as a novel nitric oxide-regulated gene in rat glomerular mesangial cells and kidneys of endotoxemic rats. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 13:869-882.
Furman, B., W.K. Ong, and N.J. Pyne. 2010. Cyclic AMP signaling in pancreatic islets. Advances in experimental medicine and biology. 654:281-304.
Gerke, V., and S.E. Moss. 1997. Annexins and membrane dynamics. Biochimica et biophysica acta. 1357:129-154.
Green, H., and M. Meuth. 1974. An established pre-adipose cell line and its differentiation in culture. Cell. 3:127-133.
Harndahl, L., N. Wierup, S. Enerback, H. Mulder, V.C. Manganiello, F. Sundler, E. Degerman, B. Ahren, and L.S. Holst. 2004. Beta-cell-targeted overexpression of phosphodiesterase 3B in mice causes impaired insulin secretion, glucose intolerance, and deranged islet morphology. The Journal of biological chemistry. 279:15214-15222.
Harrison, S.A., D.H. Reifsnyder, B. Gallis, G.G. Cadd, and J.A. Beavo. 1986. Isolation and characterization of bovine cardiac muscle cGMP-inhibited phosphodiesterase: a receptor for new cardiotonic drugs. Molecular pharmacology. 29:506-514.
He, R., N. Komas, D. Ekholm, T. Murata, M. Taira, S. Hockman, E. Degerman, and V.C. Manganiello. 1998. Expression and characterization of deletion recombinants of two cGMP-inhibited cyclic nucleotide phosphodiesterases (PDE-3). Cell biochemistry and biophysics. 29:89-111.
Hemmings, B.A., and D.F. Restuccia. 2012. PI3K-PKB/Akt pathway. Cold Spring Harbor perspectives in biology. 4:a011189.
Hillenkamp, F., and M. Karas. 1990. Mass spectrometry of peptides and proteins by matrix-assisted ultraviolet laser desorption/ionization. Methods in enzymology. 193:280-295.
Hippe, H.J., S. Lutz, F. Cuello, K. Knorr, A. Vogt, K.H. Jakobs, T. Wieland, and F. Niroomand. 2003. Activation of heterotrimeric G proteins by a high energy phosphate transfer via nucleoside diphosphate kinase (NDPK) B and Gbeta subunits. Specific activation of Gsalpha by an NDPK B.Gbetagamma complex in H10 cells. The Journal of biological chemistry. 278:7227-7233.
Hoffmann, R., G.S. Baillie, S.J. MacKenzie, S.J. Yarwood, and M.D. Houslay. 1999. The MAP kinase ERK2 inhibits the cyclic AMP-specific phosphodiesterase HSPDE4D3 by phosphorylating it at Ser579. The EMBO journal. 18:893-903.
Houslay, M.D. 2010. Underpinning compartmentalised cAMP signalling through targeted cAMP breakdown. Trends in biochemical sciences. 35:91-100.
Houslay, M.D., and D.R. Adams. 2003. PDE4 cAMP phosphodiesterases: modular enzymes that orchestrate signalling cross-talk, desensitization and compartmentalization. The Biochemical journal. 370:1-18.
Hsieh, M.S., W.B. Zhong, S.C. Yu, J.Y. Lin, W.M. Chi, and H.M. Lee. 2010. Dipyridamole suppresses high glucose-induced osteopontin secretion and mRNA expression in rat aortic smooth muscle cells. Circulation journal : official journal of the Japanese Circulation Society. 74:1242-1250.
Huang, J., S.H. Hsia, T. Imamura, I. Usui, and J.M. Olefsky. 2004. Annexin II is a thiazolidinedione-responsive gene involved in insulin-induced glucose transporter isoform 4 translocation in 3T3-L1 adipocytes. Endocrinology. 145:1579-1586.
Jia, J.J., X.S. Zeng, Y. Li, S. Ma, and J. Bai. 2013. Ephedrine induced thioredoxin-1 expression through beta-adrenergic receptor/cyclic AMP/protein kinase A/dopamine- and cyclic AMP-regulated phosphoprotein signaling pathway. Cellular signalling. 25:1194-1201.
Jin, S.L., S.L. Ding, and S.C. Lin. 2012. Phosphodiesterase 4 and its inhibitors in inflammatory diseases. Chang Gung medical journal. 35:197-210.
Jocken, J.W., and E.E. Blaak. 2008. Catecholamine-induced lipolysis in adipose tissue and skeletal muscle in obesity. Physiology & behavior. 94:219-230.
Kenan, Y., T. Murata, Y. Shakur, E. Degerman, and V.C. Manganiello. 2000. Functions of the N-terminal region of cyclic nucleotide phosphodiesterase 3 (PDE 3) isoforms. The Journal of biological chemistry. 275:12331-12338.
Kitamura, T., Y. Kitamura, S. Kuroda, Y. Hino, M. Ando, K. Kotani, H. Konishi, H. Matsuzaki, U. Kikkawa, W. Ogawa, and M. Kasuga. 1999. Insulin-induced phosphorylation and activation of cyclic nucleotide phosphodiesterase 3B by the serine-threonine kinase Akt. Molecular and cellular biology. 19:6286-6296.
Konig, J., J. Prenen, B. Nilius, and V. Gerke. 1998. The annexin II-p11 complex is involved in regulated exocytosis in bovine pulmonary artery endothelial cells. The Journal of biological chemistry. 273:19679-19684.
Kopecky, J., M. Baudysova, F. Zanotti, D. Janikova, S. Pavelka, and J. Houstek. 1990. Synthesis of mitochondrial uncoupling protein in brown adipocytes differentiated in cell culture. The Journal of biological chemistry. 265:22204-22209.
Kovala, T., B.D. Sanwal, and E.H. Ball. 1997. Recombinant expression of a type IV, cAMP-specific phosphodiesterase: characterization and structure-function studies of deletion mutants. Biochemistry. 36:2968-2976.
Kralisch, S., J. Klein, U. Lossner, M. Bluher, R. Paschke, M. Stumvoll, and M. Fasshauer. 2006. Isoproterenol stimulates monocyte chemoattractant protein-1 expression and secretion in 3T3-L1 adipocytes. Regulatory peptides. 135:12-16.
Lanne, B., F. Potthast, A. Hoglund, H. Brockenhuus von Lowenhielm, A.C. Nystrom, F. Nilsson, and B. Dahllof. 2001. Thiourea enhances mapping of the proteome from murine white adipose tissue. Proteomics. 1:819-828.
Lee, H.K., B.H. Lee, S.A. Park, and C.W. Kim. 2006. The proteomic analysis of an adipocyte differentiated from human mesenchymal stem cells using two-dimensional gel electrophoresis. Proteomics. 6:1223-1229.
Lee, O.H., M.J. Seo, H.S. Choi, and B.Y. Lee. 2012. Pycnogenol(R) inhibits lipid accumulation in 3T3-L1 adipocytes with the modulation of reactive oxygen species (ROS) production associated with antioxidant enzyme responses. Phytotherapy research : PTR. 26:403-411.
Malmquist, N.A., J.J. Anzinger, D. Hirzel, and I.L. Buxton. 2001. Ellagic acid inhibits nucleoside diphosphate kinase-B activity. Proceedings of the Western Pharmacology Society. 44:57-59.
Manganiello, V.C., M. Taira, E. Degerman, and P. Belfrage. 1995. Type III cGMP-inhibited cyclic nucleotide phosphodiesterases (PDE3 gene family). Cellular signalling. 7:445-455.
Marikovsky, M., V. Ziv, N. Nevo, C. Harris-Cerruti, and O. Mahler. 2003. Cu/Zn superoxide dismutase plays important role in immune response. Journal of immunology. 170:2993-3001.
Medzihradszky, K.F., J.M. Campbell, M.A. Baldwin, A.M. Falick, P. Juhasz, M.L. Vestal, and A.L. Burlingame. 2000. The characteristics of peptide collision-induced dissociation using a high-performance MALDI-TOF/TOF tandem mass spectrometer. Analytical chemistry. 72:552-558.
Mills, S.E., and C.Y. Liu. 1990. Sensitivity of lipolysis and lipogenesis to dibutyryl-cAMP and beta-adrenergic agonists in swine adipocytes in vitro. Journal of animal science. 68:1017-1023.
Movsesian, M.A., and R.C. Kukreja. 2011. Phosphodiesterase inhibition in heart failure. Handbook of experimental pharmacology:237-249.
O′Farrell, P.H. 1975. High resolution two-dimensional electrophoresis of proteins. The Journal of biological chemistry. 250:4007-4021.
Ochiai, M., T. Isshiki, S. Takeshita, K. Eto, H. Toyoizumi, T. Sato, and H. Miyashita. 1997. Use of cilostazol, a novel antiplatelet agent, in a post-Palmaz-Schatz stenting regimen. The American journal of cardiology. 79:1471-1474.
Oknianska, A., E. Zmuda-Trzebiatowska, V. Manganiello, and E. Degerman. 2007. Long-term regulation of cyclic nucleotide phosphodiesterase type 3B and 4 in 3T3-L1 adipocytes. Biochemical and biophysical research communications. 353:1080-1085.
Packer, M., J.R. Carver, R.J. Rodeheffer, R.J. Ivanhoe, R. DiBianco, S.M. Zeldis, G.H. Hendrix, W.J. Bommer, U. Elkayam, M.L. Kukin, and et al. 1991. Effect of oral milrinone on mortality in severe chronic heart failure. The PROMISE Study Research Group. The New England journal of medicine. 325:1468-1475.
Park, S.Y., J.H. Lee, K.Y. Kim, E.K. Kim, S.J. Yun, C.D. Kim, W.S. Lee, and K.W. Hong. 2008. Cilostazol increases 3T3-L1 preadipocyte differentiation with improved glucose uptake associated with activation of peroxisome proliferator-activated receptor-gamma transcription. Atherosclerosis. 201:258-265.
Powis, G., D. Mustacich, and A. Coon. 2000. The role of the redox protein thioredoxin in cell growth and cancer. Free radical biology & medicine. 29:312-322.
Rabe, K.F. 2010. Roflumilast for the treatment of chronic obstructive pulmonary disease. Expert review of respiratory medicine. 4:543-555.
Rahman, A., S.G. Kumar, S.W. Kim, H.J. Hwang, Y.M. Baek, S.H. Lee, H.S. Hwang, Y.H. Shon, K.S. Nam, and J.W. Yun. 2008. Proteomic analysis for inhibitory effect of chitosan oligosaccharides on 3T3-L1 adipocyte differentiation. Proteomics. 8:569-581.
Rahn Landstrom, T., J. Mei, M. Karlsson, V. Manganiello, and E. Degerman. 2000. Down-regulation of cyclic-nucleotide phosphodiesterase 3B in 3T3-L1 adipocytes induced by tumour necrosis factor alpha and cAMP. The Biochemical journal. 346 Pt 2:337-343.
Rajalingam, D., C. Loftis, J.J. Xu, and T.K. Kumar. 2009. Trichloroacetic acid-induced protein precipitation involves the reversible association of a stable partially structured intermediate. Protein science : a publication of the Protein Society. 18:980-993.
Rea, S., and D.E. James. 1997. Moving GLUT4: the biogenesis and trafficking of GLUT4 storage vesicles. Diabetes. 46:1667-1677.
Reichert, M., and D. Eick. 1999. Analysis of cell cycle arrest in adipocyte differentiation. Oncogene. 18:459-466.
Renes, J., F. Bouwman, J.P. Noben, C. Evelo, J. Robben, and E. Mariman. 2005. Protein profiling of 3T3-L1 adipocyte differentiation and (tumor necrosis factor alpha-mediated) starvation. Cellular and molecular life sciences : CMLS. 62:492-503.
Resjo, S., O. Goransson, L. Harndahl, S. Zolnierowicz, V. Manganiello, and E. Degerman. 2002. Protein phosphatase 2A is the main phosphatase involved in the regulation of protein kinase B in rat adipocytes. Cellular signalling. 14:231-238.
Resjo, S., A. Oknianska, S. Zolnierowicz, V. Manganiello, and E. Degerman. 1999. Phosphorylation and activation of phosphodiesterase type 3B (PDE3B) in adipocytes in response to serine/threonine phosphatase inhibitors: deactivation of PDE3B in vitro by protein phosphatase type 2A. The Biochemical journal. 341 ( Pt 3):839-845.
Richter, W., and M. Conti. 2002. Dimerization of the type 4 cAMP-specific phosphodiesterases is mediated by the upstream conserved regions (UCRs). The Journal of biological chemistry. 277:40212-40221.
Ross, P., L. Hall, I. Smirnov, and L. Haff. 1998. High level multiplex genotyping by MALDI-TOF mass spectrometry. Nature biotechnology. 16:1347-1351.
Rybalkin, S.D., I.G. Rybalkina, M. Shimizu-Albergine, X.B. Tang, and J.A. Beavo. 2003. PDE5 is converted to an activated state upon cGMP binding to the GAF A domain. The EMBO journal. 22:469-478.
Sea, K., S.H. Sohn, A. Durazo, Y. Sheng, B. Shaw, X. Cao, A.B. Taylor, L.J. Whitson, S.P. Holloway, P.J. Hart, D.E. Cabelli, E.B. Gralla, and J.S. Valentine. 2014. Insights into the Role of the Unusual Disulfide Bond in Copper-Zinc Superoxide Dismutase. The Journal of biological chemistry.
Shakur, Y., L.S. Holst, T.R. Landstrom, M. Movsesian, E. Degerman, and V. Manganiello. 2001. Regulation and function of the cyclic nucleotide phosphodiesterase (PDE3) gene family. Progress in nucleic acid research and molecular biology. 66:241-277.
Shakur, Y., K. Takeda, Y. Kenan, Z.X. Yu, G. Rena, D. Brandt, M.D. Houslay, E. Degerman, V.J. Ferrans, and V.C. Manganiello. 2000. Membrane localization of cyclic nucleotide phosphodiesterase 3 (PDE3). Two N-terminal domains are required for the efficient targeting to, and association of, PDE3 with endoplasmic reticulum. The Journal of biological chemistry. 275:38749-38761.
Soderling, S.H., and J.A. Beavo. 2000. Regulation of cAMP and cGMP signaling: new phosphodiesterases and new functions. Current opinion in cell biology. 12:174-179.
Suganami, T., J. Nishida, and Y. Ogawa. 2005. A paracrine loop between adipocytes and macrophages aggravates inflammatory changes: role of free fatty acids and tumor necrosis factor alpha. Arteriosclerosis, thrombosis, and vascular biology. 25:2062-2068.
Suganami, T., and Y. Ogawa. 2010. Adipose tissue macrophages: their role in adipose tissue remodeling. Journal of leukocyte biology. 88:33-39.
Sun, K., C.M. Kusminski, and P.E. Scherer. 2011. Adipose tissue remodeling and obesity. The Journal of clinical investigation. 121:2094-2101.
Sutherland, E.W., and T.W. Rall. 1958. Fractionation and characterization of a cyclic adenine ribonucleotide formed by tissue particles. The Journal of biological chemistry. 232:1077-1091.
Tani, T., K. Uehara, T. Sudo, K. Marukawa, Y. Yasuda, and Y. Kimura. 2000. Cilostazol, a selective type III phosphodiesterase inhibitor, decreases triglyceride and increases HDL cholesterol levels by increasing lipoprotein lipase activity in rats. Atherosclerosis. 152:299-305.
Thompson, P.D., R. Zimet, W.P. Forbes, and P. Zhang. 2002. Meta-analysis of results from eight randomized, placebo-controlled trials on the effect of cilostazol on patients with intermittent claudication. The American journal of cardiology. 90:1314-1319.
Thompson, P.E., V. Manganiello, and E. Degerman. 2007. Re-discovering PDE3 inhibitors--new opportunities for a long neglected target. Current topics in medicinal chemistry. 7:421-436.
Wada, T., Y. Onogi, Y. Kimura, T. Nakano, H. Fusanobori, Y. Ishii, M. Sasahara, H. Tsuneki, and T. Sasaoka. 2013. Cilostazol ameliorates systemic insulin resistance in diabetic db/db mice by suppressing chronic inflammation in adipose tissue via modulation of both adipocyte and macrophage functions. European journal of pharmacology. 707:120-129.
Waisman, D.M. 1995. Annexin II tetramer: structure and function. Molecular and cellular biochemistry. 149-150:301-322.
Walz, H.A., L. Harndahl, N. Wierup, E. Zmuda-Trzebiatowska, F. Svennelid, V.C. Manganiello, T. Ploug, F. Sundler, E. Degerman, B. Ahren, and L.S. Holst. 2006. Early and rapid development of insulin resistance, islet dysfunction and glucose intolerance after high-fat feeding in mice overexpressing phosphodiesterase 3B. The Journal of endocrinology. 189:629-641.
Walz, H.A., N. Wierup, J. Vikman, V.C. Manganiello, E. Degerman, L. Eliasson, and L.S. Holst. 2007. Beta-cell PDE3B regulates Ca2+-stimulated exocytosis of insulin. Cellular signalling. 19:1505-1513.
Wechsler, J., Y.H. Choi, J. Krall, F. Ahmad, V.C. Manganiello, and M.A. Movsesian. 2002. Isoforms of cyclic nucleotide phosphodiesterase PDE3A in cardiac myocytes. The Journal of biological chemistry. 277:38072-38078.
Wood, S.L., N. Emmison, A.C. Borthwick, and S.J. Yeaman. 1993. The protein phosphatases responsible for dephosphorylation of hormone-sensitive lipase in isolated rat adipocytes. The Biochemical journal. 295 ( Pt 2):531-535.
Zhai, W., C. Xu, Y. Ling, S. Liu, J. Deng, Y. Qi, C. Londos, and G. Xu. 2010. Increased lipolysis in adipose tissues is associated with elevation of systemic free fatty acids and insulin resistance in perilipin null mice. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 42:247-253.
Zhang, R., R. Al-Lamki, L. Bai, J.W. Streb, J.M. Miano, J. Bradley, and W. Min. 2004. Thioredoxin-2 inhibits mitochondria-located ASK1-mediated apoptosis in a JNK-independent manner. Circulation research. 94:1483-1491.
Zhang, X., and G.B. Carey. 2004. Plasma membrane-bound cyclic AMP phosphodiesterase activity in 3T3-L1 adipocytes. Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology. 137:309-316.
Zmuda-Trzebiatowska, E., A. Oknianska, V. Manganiello, and E. Degerman. 2006. Role of PDE3B in insulin-induced glucose uptake, GLUT-4 translocation and lipogenesis in primary rat adipocytes. Cellular signalling. 18:382-390.
Zoraghi, R., J.D. Corbin, and S.H. Francis. 2004. Properties and functions of GAF domains in cyclic nucleotide phosphodiesterases and other proteins. Molecular pharmacology. 65:267-278.

指導教授

金秀蓮(Shiow-Lian Cathrine Jin)

審核日期

2015-1-27

推文