簡易檢索 / 詳目顯示

研究生: 盧映潔
Lu, Ying-Chieh
論文名稱: Part I:藉由蛋白質體分析黃蓮素誘導乳癌細胞中之毒殺性機制 Part II:糖尿病 II-I:利用蛋白質體找出第一型糖尿病血漿生物標誌分子:發現 hemopexin為第一型糖尿病患者腎病血漿中新穎性生物標誌分子 II- II:藉由蛋白質體找出第二型糖尿病患者腎病血漿中生物標誌分子
Part I:Proteomic analysis of berberine-induced cytotoxicity in breast cancer cells. Part II:Diabetes mellitus (DM) II-I:Proteomic identification of plasma biomarkers in type 1 diabetic nephropathy: implicate hemopexin as a novel plasma biomarker in type 1 diabetes mellitus. II- II:Proteomic identification of plasma biomarkers in type 2 diabetic nephropathy.
指導教授: 詹鴻霖
Chan, Hong-Lin
口試委員: 周秀專
陳毓華
學位類別: 碩士
Master
系所名稱: 生命科學暨醫學院 - 生物資訊與結構生物研究所
Institute of Bioinformatics and Structural Biology
論文出版年: 2011
畢業學年度: 99
語文別: 中文
論文頁數: 203
中文關鍵詞: 黃蓮素蛋白質體乳癌糖尿病生物標誌分子
相關次數: 點閱:3下載:0
分享至:
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報
  • 黃蓮素是一種由中草藥植物「黃蓮」所分離出來的天然產物。然而,黃蓮素對乳癌上的作用效果仍尚未釐清。為了確定黃蓮素治療乳癌的有效性及其細胞毒性機制,我們藉由lysine螢光標定與cysteine螢光標定樣品蛋白進行二維差異電泳(2D-DIGE)和氧化還原二維差異電泳(Redox-DIGE)並結合基質輔助雷射脫附游離法(MALDI-TOF MS)分析黃蓮素(berberine, BBR) 處理乳癌細胞和未利用黃蓮素處理乳癌細胞之間差異表現蛋白以及氧化還原調控的蛋白。在蛋白質體學技術研究指出各別有96個以及22個蛋白質有顯著性變化和thiol基團的反應;研究指出黃蓮素誘導乳癌毒性作用的蛋白質包括蛋白質摺疊、蛋白水解、氧化還原調控、蛋白質運輸、細胞訊息、電子傳遞、代謝。綜合上面所述,我們藉由策略性蛋白質體學提供了一個快速的方法來研究黃蓮素對乳癌細胞毒性的分子機制之相關性。這些所辨識的蛋白質生物標誌分子研究結果,可能有助於未來當作有潛力的生物標誌分子,以做為往後黃蓮素對乳癌治療上進一步的評估。


    糖尿病是現代文明病之一,根據行政院衛生署調查報告指出糖尿病死亡率在2009年為台灣十大死亡率排行第五名。第一型糖尿病是先天性的疾病,多發生於兒童和青少年,因腎臟缺乏分泌胰島素的功能,因此又稱為胰島素依賴型糖尿病。近幾年來利用螢光標定樣品蛋白進行二維差異電泳(2D-DIGE)和基質輔助雷射脫附游離飛行時間質譜儀(MALDI-TOF MS)的技術提供我們探討和追蹤糖尿病血漿的蛋白質作用機制,並且發現血漿蛋白質可做為生物標誌分子。藉由蛋白質體分析第一型糖尿病和健康血漿中所有的蛋白質,我們鑑定出有39個差異表現的蛋白質,其中有37個特異性蛋白質,這些以鑑定的蛋白質hemopexin也包括在內。Hemopexin 分子量大小約為60 kDa,它與heme有高度的親和力。在我們的研究結果發現hemopexin可藉由不同的細胞(ARPE19、 Chang's、 HT29、H9c2、 Hela)在增加葡萄糖濃度的培養液培養之下而被誘導出來。有趣的是,葡萄糖所誘導出的hemopexin大量表現可以經由過氧化物抑制劑(Glutathion)減少hemopexin表現量,這個暗示hemopexin的表達與葡萄糖誘導的氧化壓力是有關聯性。綜合以上所述,第一型糖尿病可藉由蛋白質體技術確定的蛋白質找到生物標誌分子。此外據我們所知,此次實驗是第一次報告顯示可以透過血糖濃度及過氧化物之間調控hemopexin的表達。

    目錄 誌謝辭 I Part I:Proteomic analysis of berberine-induced cytotoxicity in breast cancer cells. II Part II:Diabetes mellitus (DM) II II-I:Proteomic identification of plasma biomarkers in type 1 diabetic nephropathy: implicate hemopexin as a novel plasma biomarker in type 1 diabetes mellitus. II II- II:Proteomic identification of plasma biomarkers in II type 2 diabetic nephropathy. II 摘要 III Part I:藉由蛋白質體分析黃蓮素誘導乳癌細胞中之毒殺性機制 III Part II:糖尿病 IV II-I:利用蛋白質體找出第一型糖尿病血漿生物標誌分子:發現 hemopexin為第一型糖尿病患者腎病血漿中新穎性生物標誌分子 IV II- II:藉由蛋白質體找出第二型糖尿病患者腎病血漿中生物標誌分子 V Abstract VI Part I:Proteomic analysis of berberine-induced cytotoxicity in breast cancer cells. VI Part II:Diabetes mellitus (DM) VII II-I:Proteomic identification of plasma biomarkers in type 1 diabetic nephropathy: implicate hemopexin as a novel plasma biomarker in type 1 diabetes mellitus. VII II- II:Proteomic identification of plasma biomarkers in type 2 diabetic nephropathy. VIII 目錄 IX Abbreviatation 1 Part I:Proteomic analysis of berberine-induced cytotoxicity in breast cancer cells. 4 壹、文獻探討 5 一、黃蓮素 5 二、乳癌 8 三、蛋白質體學 13 四、研究目的 39 貳、材料與方法 40 一、藥品和材料 40 二、樣品的製備 41 三、細胞存活率測定(MTT cell viability assay) 42 四、細胞內生性過氧化物測定(DCFH-DA assay) 43 五、二維差異電泳分析與影像分析 43 六、氧化還原二維差異電泳分析與影像分析 48 七、蛋白質身份鑑定 54 八、表現差異蛋白之確認 57 参、實驗結果 62 一、大範圍評估中草藥,試圖找出能夠抑制乳癌細胞生長的天然藥物 62 二、評估黃蓮素對於正常乳腺細胞的毒殺性 62 三、黃蓮素誘使MCF-7死亡 62 四、評估黃蓮素誘使MCF-7內生性產生過氧化物 63 五、分析黃蓮素IC50劑量處理MCF-7和沒有使用任何藥物處理MCF-7之間蛋白質的表現其二維差異電泳結果分析 64 六、表現量有差異的蛋白質之鑑定 64 七、蛋白質位置和功能性分類 65 八、利用西方墨點法和酵素連結免疫吸附法再次確認所鑑定到的蛋白質 66 九、分析黃蓮素處理MCF-7和沒有使用任何藥物處理MCF-7之間cysteine蛋白質修飾後的表現其氧化還原(Redox)二維差異電泳結果分析 66 十、cysteine蛋白質修飾後表現量有差異的蛋白質之鑑定 67 十一、cysteine蛋白質修飾後蛋白質位置和功能性分類 68 肆、討論 85 伍、結論 92 Reference List I 94 Part II:Diabetes mellitus (DM) 105 II-I:Proteomic identification of plasma biomarkers in type 1 diabetic nephropathy: implicate hemopexin as a novel plasma biomarker in type 1 diabetes mellitus. 105 II-II:Proteomic identification of plasma biomarkers in type 2 diabetic nephropathy. 105 壹、文獻探討 106 一、糖尿病與糖類代謝系統 106 二、糖尿病 108 三、血清蛋白質體學(Serum proteomics) 120 四、研究目的 124 貳、材料與方法 125 一、藥品和材料來源 125 二、蛋白質樣品的製備與純化 127 三、二維差異電泳分析與影像分析 131 四、蛋白質身份鑑定 136 五、細胞存活率測定(MTT cell viability assay) 138 六、細胞內生性過氧化物測定(DCFH-DA assay) 138 七、GSH(glutathion)抗氧化劑的應用 139 八、表現差異蛋白之確認 139 参、實驗結果 143 一、分析第一型和第二型糖尿病與相對年齡正常人血清之間樣品蛋白質的表現其二維差異電泳結果分析 143 二、第一型及第二型糖尿病表現量有差異的蛋白質之鑑定 144 三、第一型及第二型糖尿病蛋白質位置和功能性分類 145 四、利用臨床血清樣品結合西方墨點法和酵素連結免疫吸附法再次確認所鑑定到的蛋白質 146 五、從細胞的層面偵測hemopexin在第一型糖尿病生理狀態時的表現量 147 六、從細胞的層面分析第一型糖尿病高糖濃度所誘導生成的過氧化物hemopexin表現量之間的相關性 148 肆、討論 170 伍、結論 177 Reference List II 180 附錄 187

    Alberts,A.S. and Treisman,R. (1998). Activation of RhoA and SAPK/JNK signalling pathways by the RhoA-specific exchange factor mNET1. EMBO J. 17, 4075-4085.
    Babbar,O.P., Chhatwal,V.K., Ray,I.B., and Mehra,M.K. (1982). Effect of berberine chloride eye drops on clinically positive trachoma patients. Indian J. Med. Res. 76 Suppl, 83-88.
    Baneshi,M.R., Warner,P., Anderson,N., Edwards,J., Cooke,T.G., and Bartlett,J.M. (2010). Tamoxifen resistance in early breast cancer: statistical modelling of tissue markers to improve risk prediction. Br. J. Cancer 102, 1503-1510.
    Barrios,C.H., Sampaio,C., Vinholes,J., and Caponero,R. (2009). What is the role of chemotherapy in estrogen receptor-positive, advanced breast cancer? Ann. Oncol. 20, 1157-1162.
    Baty,J.W., Hampton,M.B., and Winterbourn,C.C. (2002). Detection of oxidant sensitive thiol proteins by fluorescence labeling and two-dimensional electrophoresis. Proteomics. 2, 1261-1266.
    Bonfils,C., Bec,N., Larroque,C., Del Rio,M., Gongora,C., Pugniere,M., and Martineau,P. (2010). Cyclophilin A as negative regulator of apoptosis by sequestering cytochrome c. Biochem. Biophys. Res. Commun. 393, 325-330.
    Carr,S.A., Huddleston,M.J., and Annan,R.S. (1996). Selective detection and sequencing of phosphopeptides at the femtomole level by mass spectrometry. Anal. Biochem. 239, 180-192.
    Cailleau,R., Young,R., Olive,M., and Reeves,W.J., Jr. (1974). Breast tumor cell lines from pleural effusions. J. Natl. Cancer Inst. 53, 661-674.
    Chan,H.L., Gharbi,S., Gaffney,P.R., Cramer,R., Waterfield,M.D., and Timms,J.F. (2005). Proteomic analysis of redox- and ErbB2-dependent changes in mammary luminal epithelial cells using cysteine- and lysine-labelling two-dimensional difference gel electrophoresis. Proteomics. 5, 2908-2926.
    Cai,R.L., Yan-Neale,Y., Cueto,M.A., Xu,H., and Cohen,D. (2000). HDAC1, a histone deacetylase, forms a complex with Hus1 and Rad9, two G2/M checkpoint Rad proteins. J. Biol. Chem. 275, 27909-27916.
    Chan,H.L., Gaffney,P.R., Waterfield,M.D., Anderle,H., Peter,M.H., Schwarz,H.P., Turecek,P.L., and Timms,J.F. (2006). Proteomic analysis of UVC irradiation-induced damage of plasma proteins: Serum amyloid P component as a major target of photolysis. FEBS Lett. 580, 3229-3236.
    Chang,X.Z., Li,D.Q., Hou,Y.F., Wu,J., Lu,J.S., Di,G.H., Jin,W., Ou,Z.L., Shen,Z.Z., and Shao,Z.M. (2007). Identification of the functional role of peroxiredoxin 6 in the progression of breast cancer. Breast Cancer Res. 9, R76.
    Chen,T.C., Lai,K.C., Yang,J.S., Liao,C.L., Hsia,T.C., Chen,G.W., Lin,J.J., Lin,H.J., Chiu,T.H., Tang,Y.J., and Chung,J.G. (2009). Involvement of reactive oxygen species and caspase-dependent pathway in berberine-induced cell cycle arrest and apoptosis in C6 rat glioma cells. Int. J. Oncol. 34, 1681-1690.
    Chen,Y.W., Chou,H.C., Lyu,P.C., Yin,H.S., Huang,F.L., Chang,W.S., Fan,C.Y., Tu,I.F., Lai,T.C., Lin,S.T., Lu,Y.C., Wu,C.L., Huang,S.H., and Chan,H.L. (2011). Mitochondrial proteomics analysis of tumorigenic and metastatic breast cancer markers. Funct. Integr. Genomics 11, 225-239.
    Cho,B.J., Im,E.K., Kwon,J.H., Lee,K.H., Shin,H.J., Oh,J., Kang,S.M., Chung,J.H., and Jang,Y. (2005). Berberine inhibits the production of lysophosphatidylcholine-induced reactive oxygen species and the ERK1/2 pathway in vascular smooth muscle cells. Mol. Cells 20, 429-434.
    Cross,J.V. and Templeton,D.J. (2006). Regulation of signal transduction through protein cysteine oxidation. Antioxid. Redox. Signal. 8, 1819-1827.
    Danes,C.G., Wyszomierski,S.L., Lu,J., Neal,C.L., Yang,W., and Yu,D. (2008). 14-3-3 zeta down-regulates p53 in mammary epithelial cells and confers luminal filling. Cancer Res. 68, 1760-1767.
    Danial,N.N., Gramm,C.F., Scorrano,L., Zhang,C.Y., Krauss,S., Ranger,A.M., Datta,S.R., Greenberg,M.E., Licklider,L.J., Lowell,B.B., Gygi,S.P., and Korsmeyer,S.J. (2003). BAD and glucokinase reside in a mitochondrial complex that integrates glycolysis and apoptosis. Nature 424, 952-956.
    Danial,N.N., Walensky,L.D., Zhang,C.Y., Choi,C.S., Fisher,J.K., Molina,A.J., Datta,S.R., Pitter,K.L., Bird,G.H., Wikstrom,J.D., Deeney,J.T., Robertson,K., Morash,J., Kulkarni,A., Neschen,S., Kim,S., Greenberg,M.E., Corkey,B.E., Shirihai,O.S., Shulman,G.I., Lowell,B.B., and Korsmeyer,S.J. (2008). Dual role of proapoptotic BAD in insulin secretion and beta cell survival. Nat. Med. 14, 144-153.
    Dobrzycka,K.M., Townson,S.M., Jiang,S., and Oesterreich,S. (2003). Estrogen receptor corepressors -- a role in human breast cancer? Endocr. Relat Cancer 10, 517-536.
    EDMAN,P. (1949). A method for the determination of amino acid sequence in peptides. Arch. Biochem. 22, 475.
    Eom,K.S., Kim,H.J., So,H.S., Park,R., and Kim,T.Y. (2010). Berberine-induced apoptosis in human glioblastoma T98G cells is mediated by endoplasmic reticulum stress accompanying reactive oxygen species and mitochondrial dysfunction. Biol. Pharm. Bull. 33, 1644-1649.
    Fatma,N., Kubo,E., Sen,M., Agarwal,N., Thoreson,W.B., Camras,C.B., and Singh,D.P. (2008). Peroxiredoxin 6 delivery attenuates TNF-alpha-and glutamate-induced retinal ganglion cell death by limiting ROS levels and maintaining Ca2+ homeostasis. Brain Res. 1233, 63-78.
    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.
    Garcia,A., Cayla,X., Guergnon,J., Dessauge,F., Hospital,V., Rebollo,M.P., Fleischer,A., and Rebollo,A. (2003). Serine/threonine protein phosphatases PP1 and PP2A are key players in apoptosis. Biochimie 85, 721-726.
    Ghezzi,P., Bonetto,V., and Fratelli,M. (2005). Thiol-disulfide balance: from the concept of oxidative stress to that of redox regulation. Antioxid. Redox. Signal. 7, 964-972.
    Giacinti,C. and Giordano,A. (2006). RB and cell cycle progression. Oncogene 25, 5220-5227.
    Gu,W., Luo,J., Brooks,C.L., Nikolaev,A.Y., and Li,M. (2004). Dynamics of the p53 acetylation pathway. Novartis. Found. Symp. 259, 197-205.
    Gorg,A., Weiss,W., and Dunn,M.J. (2004). Current two-dimensional electrophoresis technology for proteomics. Proteomics. 4, 3665-3685.
    Hackshaw,A.K. and Paul,E.A. (2003). Breast self-examination and death from breast cancer: a meta-analysis. Br. J. Cancer 88, 1047-1053.
    Hansen,R.K., Parra,I., Lemieux,P., Oesterreich,S., Hilsenbeck,S.G., and Fuqua,S.A. (1999). Hsp27 overexpression inhibits doxorubicin-induced apoptosis in human breast cancer cells. Breast Cancer Res. Treat. 56, 187-196.
    He,B., Feng,Q., Mukherjee,A., Lonard,D.M., DeMayo,F.J., Katzenellenbogen,B.S., Lydon,J.P., and O'Malley,B.W. (2008). A repressive role for prohibitin in estrogen signaling. Mol. Endocrinol. 22, 344-360.
    Ho,Y.T., Lu,C.C., Yang,J.S., Chiang,J.H., Li,T.C., Ip,S.W., Hsia,T.C., Liao,C.L., Lin,J.G., Wood,W.G., and Chung,J.G. (2009). Berberine induced apoptosis via promoting the expression of caspase-8, -9 and -3, apoptosis-inducing factor and endonuclease G in SCC-4 human tongue squamous carcinoma cancer cells. Anticancer Res. 29, 4063-4070.
    Hsu,W.H., Hsieh,Y.S., Kuo,H.C., Teng,C.Y., Huang,H.I., Wang,C.J., Yang,S.F., Liou,Y.S., and Kuo,W.H. (2007). Berberine induces apoptosis in SW620 human colonic carcinoma cells through generation of reactive oxygen species and activation of JNK/p38 MAPK and FasL. Arch. Toxicol. 81, 719-728.
    Hwang,J.M., Kuo,H.C., Tseng,T.H., Liu,J.Y., and Chu,C.Y. (2006). Berberine induces apoptosis through a mitochondria/caspases pathway in human hepatoma cells. Arch. Toxicol. 80, 62-73.
    Henzel,W.J., Billeci,T.M., Stults,J.T., Wong,S.C., Grimley,C., and Watanabe,C. (1993). Identifying proteins from two-dimensional gels by molecular mass searching of peptide fragments in protein sequence databases. Proc. Natl. Acad. Sci. U. S. A 90, 5011-5015.
    Hirano,H. (2004). [Two-dimensional electrophoresis and proteomics]. Seikagaku 76, 1320-1327.
    Horwitz,K.B., Costlow,M.E., and McGuire,W.L. (1975). MCF-7; a human breast cancer cell line with estrogen, androgen, progesterone, and glucocorticoid receptors. Steroids 26, 785-795.
    Hsu,W.H., Hsieh,Y.S., Kuo,H.C., Teng,C.Y., Huang,H.I., Wang,C.J., Yang,S.F., Liou,Y.S., and Kuo,W.H. (2007). Berberine induces apoptosis in SW620 human colonic carcinoma cells through generation of reactive oxygen species and activation of JNK/p38 MAPK and FasL. Arch. Toxicol. 81, 719-728.
    Iizuka,N., Miyamoto,K., Okita,K., Tangoku,A., Hayashi,H., Yosino,S., Abe,T., Morioka,T., Hazama,S., and Oka,M. (2000). Inhibitory effect of Coptidis Rhizoma and berberine on the proliferation of human esophageal cancer cell lines. Cancer Lett. 148, 19-25.
    Ikram,M. (1975). A review on the chemical and pharmacological aspects of genus Berberis. Planta Med. 28, 353-358.
    James,P., Quadroni,M., Carafoli,E., and Gonnet,G. (1993). Protein identification by mass profile fingerprinting. Biochem. Biophys. Res. Commun. 195, 58-64.
    Jantova,S., Cipak,L., Cernakova,M., and Kost'alova,D. (2003). Effect of berberine on proliferation, cell cycle and apoptosis in HeLa and L1210 cells. J. Pharm. Pharmacol. 55, 1143-1149.
    Jemal,A., Bray,F., Center,M.M., Ferlay,J., Ward,E., and Forman,D. (2011). Global cancer statistics. CA Cancer J. Clin. 61, 69-90.
    JOHNSON,C.C., JOHNSON,G., and POE,C.F. (1952). Toxicity of alkaloids to certain bacteria. II. Berberine, physostigmine, and sanguinarine. Acta Pharmacol. Toxicol. (Copenh) 8, 71-78.
    Jordan,V.C. (2008). Tamoxifen: catalyst for the change to targeted therapy. Eur. J. Cancer 44, 30-38.
    Karas,M. and Hillenkamp,F. (1988). Laser desorption ionization of proteins with molecular masses exceeding 10,000 daltons. Anal. Chem. 60, 2299-2301.
    Katiyar,S.K., Meeran,S.M., Katiyar,N., and Akhtar,S. (2009). p53 Cooperates berberine-induced growth inhibition and apoptosis of non-small cell human lung cancer cells in vitro and tumor xenograft growth in vivo. Mol. Carcinog. 48, 24-37.
    Kim,J.B., Lee,K.M., Ko,E., Han,W., Lee,J.E., Shin,I., Bae,J.Y., Kim,S., and Noh,D.Y. (2008). Berberine inhibits growth of the breast cancer cell lines MCF-7 and MDA-MB-231. Planta Med. 74, 39-42.
    Kim,J.B., Yu,J.H., Ko,E., Lee,K.W., Song,A.K., Park,S.Y., Shin,I., Han,W., and Noh,D.Y. (2010). The alkaloid Berberine inhibits the growth of Anoikis-resistant MCF-7 and MDA-MB-231 breast cancer cell lines by inducing cell cycle arrest. Phytomedicine. 17, 436-440.
    Kondo,T. and Hirohashi,S. (2009). Application of 2D-DIGE in cancer proteomics toward personalized medicine. Methods Mol. Biol. 577, 135-154.
    Kuo,C.L., Chi,C.W., and Liu,T.Y. (2005). Modulation of apoptosis by berberine through inhibition of cyclooxygenase-2 and Mcl-1 expression in oral cancer cells. In Vivo 19, 247-252.
    Kemp,M., Go,Y.M., and Jones,D.P. (2008). Nonequilibrium thermodynamics of thiol/disulfide redox systems: a perspective on redox systems biology. Free Radic. Biol. Med. 44, 921-937.
    Klumpp,S. and Krieglstein,J. (2002). Serine/threonine protein phosphatases in apoptosis. Curr. Opin. Pharmacol. 2, 458-462.
    Kuwabara,M., Takahashi,K., and Inanami,O. (2003). Induction of apoptosis through the activation of SAPK/JNK followed by the expression of death receptor Fas in X-irradiated cells. J. Radiat. Res. (Tokyo) 44, 203-209.
    Lai,T.C., Chou,H.C., Chen,Y.W., Lee,T.R., Chan,H.T., Shen,H.H., Lee,W.T., Lin,S.T., Lu,Y.C., Wu,C.L., and Chan,H.L. (2010). Secretomic and proteomic analysis of potential breast cancer markers by two-dimensional differential gel electrophoresis. J. Proteome. Res. 9, 1302-1322.
    Lin,C.C., Yang,J.S., Chen,J.T., Fan,S., Yu,F.S., Yang,J.L., Lu,C.C., Kao,M.C., Huang,A.C., Lu,H.F., and Chung,J.G. (2007). Berberine induces apoptosis in human HSC-3 oral cancer cells via simultaneous activation of the death receptor-mediated and mitochondrial pathway. Anticancer Res. 27, 3371-3378.
    Lander,E.S., Linton,L.M., Birren,B., Nusbaum,C., Zody,M.C., Baldwin,J., Devon,K., Dewar,K., Doyle,M., FitzHugh,W., and Funke,R.(2001). Initial sequencing and analysis of the human genome. Nature 409, 860-921.
    Lin,D., Tabb,D.L., and Yates,J.R., III (2003). Large-scale protein identification using mass spectrometry. Biochim. Biophys. Acta 1646, 1-10.
    Lippman,M.E. and Bolan,G. (1975). Oestrogen-responsive human breast cancer in long term tissue culture. Nature 256, 592-593.
    Liu J, He C, Zhou K, Wang J, Kang JX.(2009). Coptis extracts enhance the anticancer effect of estrogen receptor antagonists on human breast cancer cells.J. BBRC.378, 174-178.
    Makino,K., Umeda,K., Uezu,A., Hiragami,Y., Sakamoto,T., Ihn,H., and Nakanishi,H. (2008). Identification and characterization of the novel centrosomal protein centlein. Biochem. Biophys. Res. Commun. 366, 958-962.
    McCallum,J.F., Wise,A., Grassie,M.A., Magee,A.I., Guzzi,F., Parenti,M., and Milligan,G. (1995). The role of palmitoylation of the guanine nucleotide binding protein G11 alpha in defining interaction with the plasma membrane. Biochem. J. 310 ( Pt 3), 1021-1027.
    McClung,J.K., Jupe,E.R., Liu,X.T., and Dell'Orco,R.T. (1995). Prohibitin: potential role in senescence, development, and tumor suppression. Exp. Gerontol. 30, 99-124.
    Meeran,S.M., Katiyar,S., and Katiyar,S.K. (2008). Berberine-induced apoptosis in human prostate cancer cells is initiated by reactive oxygen species generation. Toxicol. Appl. Pharmacol. 229, 33-43.
    Moran,L.K., Gutteridge,J.M., and Quinlan,G.J. (2001). Thiols in cellular redox signalling and control. Curr. Med. Chem. 8, 763-772.
    Mosser,D.D. and Morimoto,R.I. (2004). Molecular chaperones and the stress of oncogenesis. Oncogene 23, 2907-2918.
    Mann,M., Hojrup,P., and Roepstorff,P. (1993). Use of mass spectrometric molecular weight information to identify proteins in sequence databases. Biol. Mass Spectrom. 22, 338-345.
    Mantena,S.K., Sharma,S.D., and Katiyar,S.K. (2006). Berberine, a natural product, induces G1-phase cell cycle arrest and caspase-3-dependent apoptosis in human prostate carcinoma cells. Mol. Cancer Ther. 5, 296-308.
    Meeran,S.M., Katiyar,S., and Katiyar,S.K. (2008). Berberine-induced apoptosis in human prostate cancer cells is initiated by reactive oxygen species generation. Toxicol. Appl. Pharmacol. 229, 33-43.
    O'Farrell,P.H. (1975). High resolution two-dimensional electrophoresis of proteins. J. Biol. Chem. 250, 4007-4021.
    Pappin,D.J., Hojrup,P., and Bleasby,A.J. (1993). Rapid identification of proteins by peptide-mass fingerprinting. Curr. Biol. 3, 327-332.
    Peng,P.L., Hsieh,Y.S., Wang,C.J., Hsu,J.L., and Chou,F.P. (2006). Inhibitory effect of berberine on the invasion of human lung cancer cells via decreased productions of urokinase-plasminogen activator and matrix metalloproteinase-2. Toxicol. Appl. Pharmacol. 214, 8-15.
    Przedborski,S. (2007). Peroxiredoxin-2 links Cdk5 to neurodegeneration. Nat. Med. 13, 907-909.
    RAYMOND,S. and WEINTRAUB,L. (1959). Acrylamide gel as a supporting medium for zone electrophoresis. Science 130, 711.
    Sarna,L.K., Wu,N., Hwang,S.Y., Siow,Y.L., and O K (2010). Berberine inhibits NADPH oxidase mediated superoxide anion production in macrophages. Can. J. Physiol Pharmacol. 88, 369-378.
    Shenton,D. and Grant,C.M. (2003). Protein S-thiolation targets glycolysis and protein synthesis in response to oxidative stress in the yeast Saccharomyces cerevisiae. Biochem. J. 374, 513-519.
    Singh,B., Berry,J.A., Vincent,L.E., and Lucci,A. (2006). Involvement of IL-8 in COX-2-mediated bone metastases from breast cancer. J. Surg. Res. 134, 44-51.
    Shapiro,A.L., Vinuela,E., and Maizel,J.V., Jr. (1967). Molecular weight estimation of polypeptide chains by electrophoresis in SDS-polyacrylamide gels. Biochem. Biophys. Res. Commun. 28, 815-820.
    Swatton,J.E., Prabakaran,S., Karp,N.A., Lilley,K.S., and Bahn,S. (2004). Protein profiling of human postmortem brain using 2-dimensional fluorescence difference gel electrophoresis (2-D DIGE). Mol. Psychiatry 9, 128-143.
    Tan,Y.L., Goh,D., and Ong,E.S. (2006). Investigation of differentially expressed proteins due to the inhibitory effects of berberine in human liver cancer cell line HepG2. Mol. Biosyst. 2, 250-258.
    Timms,J.F. and Cramer,R. (2008). Difference gel electrophoresis. Proteomics. 8, 4886-4897.
    Turner,N., Li,J.Y., Gosby,A., To,S.W., Cheng,Z., Miyoshi,H., Taketo,M.M., Cooney,G.J., Kraegen,E.W., James,D.E., Hu,L.H., Li,J., and Ye,J.M. (2008). Berberine and its more biologically available derivative, dihydroberberine, inhibit mitochondrial respiratory complex I: a mechanism for the action of berberine to activate AMP-activated protein kinase and improve insulin action. Diabetes 57, 1414-1418.
    Timms,J.F. and Cramer,R. (2008). Difference gel electrophoresis. Proteomics. 8, 4886-4897.
    Tiselius,A. (1937). Electrophoresis of serum globulin. I. Biochem. J. 31, 313-317.
    Utz,P.J. and Anderson,P. (2000). Life and death decisions: regulation of apoptosis by proteolysis of signaling molecules. Cell Death. Differ. 7, 589-602.
    Venter,J.C., Adams,M.D., Myers,E.W., Li,P.W., Mural,R.J., Sutton,G.G., Smith,H.O., Yandell,M., Evans,C.A., and Holt,R.A.(2001). The sequence of the human genome. Science 291, 1304-1351.
    Vogl,T., Roth,J., Sorg,C., Hillenkamp,F., and Strupat,K. (1999). Calcium-induced noncovalently linked tetramers of MRP8 and MRP14 detected by ultraviolet matrix-assisted laser desorption/ionization mass spectrometry. J. Am. Soc. Mass Spectrom. 10, 1124-1130.
    Wasinger,V.C., Cordwell,S.J., Cerpa-Poljak,A., Yan,J.X., Gooley,A.A., Wilkins,M.R., Duncan,M.W., Harris,R., Williams,K.L., and Humphery-Smith,I. (1995a). Progress with gene-product mapping of the Mollicutes: Mycoplasma genitalium. Electrophoresis 16, 1090-1094.
    Wasinger,V.C., Cordwell,S.J., Cerpa-Poljak,A., Yan,J.X., Gooley,A.A., Wilkins,M.R., Duncan,M.W., Harris,R., Williams,K.L., and Humphery-Smith,I. (1995b). Progress with gene-product mapping of the Mollicutes: Mycoplasma genitalium. Electrophoresis 16, 1090-1094.
    Wade,P.A. (2001). Transcriptional control at regulatory checkpoints by histone deacetylases: molecular connections between cancer and chromatin. Hum. Mol. Genet. 10, 693-698.
    Wang,C. and Youle,R.J. (2009). The role of mitochondria in apoptosis*. Annu. Rev. Genet. 43, 95-118.
    Wang,Y., Ji,P., Liu,J., Broaddus,R.R., Xue,F., and Zhang,W. (2009). Centrosome-associated regulators of the G(2)/M checkpoint as targets for cancer therapy. Mol. Cancer 8, 8.
    Weeks,M.E., Sinclair,J., Butt,A., Chung,Y.L., Worthington,J.L., Wilkinson,C.R., Griffiths,J., Jones,N., Waterfield,M.D., and Timms,J.F. (2006). A parallel proteomic and metabolomic analysis of the hydrogen peroxide- and Sty1p-dependent stress response in Schizosaccharomyces pombe. Proteomics. 6, 2772-2796.
    Wilkie,T.M., Gilbert,D.J., Olsen,A.S., Chen,X.N., Amatruda,T.T., Korenberg,J.R., Trask,B.J., de Jong,P., Reed,R.R., Simon,M.I., and . (1992). Evolution of the mammalian G protein alpha subunit multigene family. Nat. Genet. 1, 85-91.
    Westermeier,R. and Scheibe,B. (2008). Difference gel electrophoresis based on lys/cys tagging. Methods Mol. Biol. 424, 73-85.
    Wilm,M., Neubauer,G., and Mann,M. (1996). Parent ion scans of unseparated peptide mixtures. Anal. Chem. 68, 527-533.
    Wu,M., Wang,J., and Liu,L.T. (2010). Advance of studies on anti-atherosclerosis mechanism of berberine. Chin J. Integr. Med. 16, 188-192.
    Xu,Y., Wang,Y., Yan,L., Liang,R.M., Dai,B.D., Tang,R.J., Gao,P.H., and Jiang,Y.Y. (2009a). Proteomic analysis reveals a synergistic mechanism of fluconazole and berberine against fluconazole-resistant Candida albicans: endogenous ROS augmentation. J. Proteome. Res. 8, 5296-5304.
    Xu,Y., Wang,Y., Yan,L., Liang,R.M., Dai,B.D., Tang,R.J., Gao,P.H., and Jiang,Y.Y. (2009b). Proteomic analysis reveals a synergistic mechanism of fluconazole and berberine against fluconazole-resistant Candida albicans: endogenous ROS augmentation. J. Proteome. Res. 8, 5296-5304.
    Yates,J.R., III, Speicher,S., Griffin,P.R., and Hunkapiller,T. (1993). Peptide mass maps: a highly informative approach to protein identification. Anal. Biochem. 214, 397-408.
    Yin,J., Gao,Z., Liu,D., Liu,Z., and Ye,J. (2008). Berberine improves glucose metabolism through induction of glycolysis. Am. J. Physiol Endocrinol. Metab 294, E148-E156.
    Yu,H.H., Kim,K.J., Cha,J.D., Kim,H.K., Lee,Y.E., Choi,N.Y., and You,Y.O. (2005). Antimicrobial activity of berberine alone and in combination with ampicillin or oxacillin against methicillin-resistant Staphylococcus aureus. J. Med. Food 8, 454-461.
    Zhang,H., Wei,J., Xue,R., Wu,J.D., Zhao,W., Wang,Z.Z., Wang,S.K., Zhou,Z.X., Song,D.Q., Wang,Y.M., Pan,H.N., Kong,W.J., and Jiang,J.D. (2010). Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin receptor expression. Metabolism 59, 285-292.
    Zhang,Z., Yamashita,H., Toyama,T., Sugiura,H., Ando,Y., Mita,K., Hamaguchi,M., Hara,Y., Kobayashi,S., and Iwase,H. (2005). Quantitation of HDAC1 mRNA expression in invasive carcinoma of the breast*. Breast Cancer Res. Treat. 94, 11-16.

    Zimny-Arndt,U., Schmid,M., Ackermann,R., and Jungblut,P.R. (2009). Classical proteomics: two-dimensional electrophoresis/MALDI mass spectrometry. Methods Mol. Biol. 492, 65-91.

    (2010). Standards of medical care in diabetes--2010. Diabetes Care 33 Suppl 1, S11-S61.
    (2011a). Diagnosis and classification of diabetes mellitus. Diabetes Care 34 Suppl 1, S62-S69.
    (2011b). Standards of medical care in diabetes--2011. Diabetes Care 34 Suppl 1, S11-S61.
    Ahmed,M., Neville,M.J., Edelmann,M.J., Kessler,B.M., and Karpe,F. (2010). Proteomic analysis of human adipose tissue after rosiglitazone treatment shows coordinated changes to promote glucose uptake. Obesity. (Silver. Spring) 18, 27-34.
    Altruda,F., Poli,V., Restagno,G., Argos,P., Cortese,R., and Silengo,L. (1985). The primary structure of human hemopexin deduced from cDNA sequence: evidence for internal, repeating homology. Nucleic Acids Res. 13, 3841-3859.
    Bakker,W.W., Donker,R.B., Timmer,A., van Pampus,M.G., van Son,W.J., Aarnoudse,J.G., van Goor,H., Niezen-Koning,K.E., Navis,G., Borghuis,T., Jongman,R.M., and Faas,M.M. (2007). Plasma hemopexin activity in pregnancy and preeclampsia. Hypertens. Pregnancy. 26, 227-239.
    Baricault,L., Denariaz,G., Houri,J.J., Bouley,C., Sapin,C., and Trugnan,G. (1995). Use of HT-29, a cultured human colon cancer cell line, to study the effect of fermented milks on colon cancer cell growth and differentiation. Carcinogenesis 16, 245-252.
    Bonkovsky,H.L. (1991). Iron and the liver. Am. J. Med. Sci. 301, 32-43.
    Bookchin,R.M. and Gallop,P.M. (1968). Structure of hemoglobin AIc: nature of the N-terminal beta chain blocking group. Biochem. Biophys. Res. Commun. 32, 86-93.
    Chang,R.S. (1978). HeLa marker chromosomes, Chang liver cells, and liver-specific functions. Science 199, 567-568.
    Crawford,T.N., Alfaro,D.V., III, Kerrison,J.B., and Jablon,E.P. (2009). Diabetic retinopathy and angiogenesis. Curr. Diabetes Rev. 5, 8-13.
    Coombes,K.R., Morris,J.S., Hu,J., Edmonson,S.R., and Baggerly,K.A. (2005). Serum proteomics profiling--a young technology begins to mature. Nat. Biotechnol. 23, 291-292.
    Dunn,K.C., Aotaki-Keen,A.E., Putkey,F.R., and Hjelmeland,L.M. (1996). ARPE-19, a human retinal pigment epithelial cell line with differentiated properties. Exp. Eye Res. 62, 155-169.
    Fantini,J., Bolmont,C., and Yahi,N. (1992). Tumor necrosis factor-alpha stimulates both apical and basal production of HIV in polarized human intestinal HT29 cells. Immunol. Lett. 34, 85-90.
    Fernandez-Martinez,A., Molla,B., Mayoral,R., Bosca,L., Casado,M., and Martin-Sanz,P. (2006). Cyclo-oxygenase 2 expression impairs serum-withdrawal-induced apoptosis in liver cells. Biochem. J. 398, 371-380.
    Forgue-Lafitte,M.E., Coudray,A.M., Breant,B., and Mester,J. (1989). Proliferation of the human colon carcinoma cell line HT29: autocrine growth and deregulated expression of the c-myc oncogene. Cancer Res. 49, 6566-6571.
    Foidart,M., Liem,H.H., Adornato,B.T., Engel,W.K., and Muller-Eberhard,U. (1983). Hemopexin metabolism in patients with altered serum levels. J. Lab Clin. Med. 102, 838-846.
    Field,S.F., Howson,J.M., Smyth,D.J., Walker,N.M., Dunger,D.B., and Todd,J.A. (2007). Analysis of the type 2 diabetes gene, TCF7L2, in 13,795 type 1 diabetes cases and control subjects. Diabetologia 50, 212-213.
    Gebre-Medhin,M., Ewald,U., and Tuvemo,T. (1985). Reduced serum proteins in diabetic children on a twice-daily insulin schedule. Acta Paediatr. Scand. 74, 961-965.
    Goodarzi,M.T., Navidi,A.A., Rezaei,M., and Babahmadi-Rezaei,H. (2010). Oxidative damage to DNA and lipids: correlation with protein glycation in patients with type 1 diabetes. J. Clin. Lab Anal. 24, 72-76.
    Haller,K., Kisand,K., Pisarev,H., Salur,L., Laisk,T., Nemvalts,V., and Uibo,R. (2007). Insulin gene VNTR, CTLA-4 +49A/G and HLA-DQB1 alleles distinguish latent autoimmune diabetes in adults from type 1 diabetes and from type 2 diabetes group. Tissue Antigens 69, 121-127.
    Heyes,G.J. and Mill,A.J. (2004). The neoplastic transformation potential of mammography X rays and atomic bomb spectrum radiation. Radiat. Res. 162, 120-127.
    Himsworth,H.P. (1932). TEMPORARY VISUAL DISTURBANCE AS AN INITIAL SYMPTOM OF DIABETES MELLITUS. Br. Med. J. 2, 1184-1186.
    HUISMAN,T.H., MARTIS,E.A., and DOZY,A. (1958). Chromatography of hemoglobin types on carboxymethylcellulose. J. Lab Clin. Med. 52, 312-327.
    Hunt,R.C., Handy,I., and Smith,A. (1996a). Heme-mediated reactive oxygen species toxicity to retinal pigment epithelial cells is reduced by hemopexin. J. Cell Physiol 168, 81-86.
    Hunt,R.C., Hunt,D.M., Gaur,N., and Smith,A. (1996b). Hemopexin in the human retina: protection of the retina against heme-mediated toxicity. J. Cell Physiol 168, 71-80.
    Issaq,H.J., Xiao,Z., and Veenstra,T.D. (2007). Serum and plasma proteomics. Chem. Rev. 107, 3601-3620.
    Kaneto,H., Katakami,N., Matsuhisa,M., and Matsuoka,T.A. (2010). Role of reactive oxygen species in the progression of type 2 diabetes and atherosclerosis. Mediators. Inflamm. 2010, 453892.
    Kim,H.J., Cho,E.H., Yoo,J.H., Kim,P.K., Shin,J.S., Kim,M.R., and Kim,C.W. (2007). Proteome analysis of serum from type 2 diabetics with nephropathy. J. Proteome. Res. 6, 735-743.
    Kang-Park,S., Im,J.H., Lee,J.H., and Lee,Y.I. (2006). PTEN modulates hepatitis B virus-X protein induced survival signaling in Chang liver cells. Virus Res. 122, 53-60.
    Kimes,B.W. and Brandt,B.L. (1976). Properties of a clonal muscle cell line from rat heart. Exp. Cell Res. 98, 367-381.
    Koenig,R.J., Peterson,C.M., Jones,R.L., Saudek,C., Lehrman,M., and Cerami,A. (1976). Correlation of glucose regulation and hemoglobin AIc in diabetes mellitus. N. Engl. J. Med. 295, 417-420.
    Koffler,M., Raskin,P., Geyer,O., and Yust,I. (1990). Blurred vision: an overlooked initial presenting symptom of insulin-dependent diabetes mellitus. Isr. J. Med. Sci. 26, 393-394.
    Korc,M. (2003). Diabetes mellitus in the era of proteomics. Mol. Cell Proteomics. 2, 399-404.
    Lavery,G.G., McTernan,C.L., Bain,S.C., Chowdhury,T.A., Hewison,M., and Stewart,P.M. (2002). Association studies between the HSD11B2 gene (encoding human 11beta-hydroxysteroid dehydrogenase type 2), type 1 diabetes mellitus and diabetic nephropathy. Eur. J. Endocrinol. 146, 553-558.
    Li,R.X., Chen,H.B., Tu,K., Zhao,S.L., Zhou,H., Li,S.J., Dai,J., Li,Q.R., Nie,S., Li,Y.X., Jia,W.P., Zeng,R., and Wu,J.R. (2008). Localized-statistical quantification of human serum proteome associated with type 2 diabetes. PLoS. One. 3, e3224.
    Liu,X., Feng,Q., Chen,Y., Zuo,J., Gupta,N., Chang,Y., and Fang,F. (2009). Proteomics-based identification of differentially-expressed proteins including galectin-1 in the blood plasma of type 2 diabetic patients. J. Proteome. Res. 8, 1255-1262.
    Lopez,M., Lage,R., Saha,A.K., Perez-Tilve,D., Vazquez,M.J., Varela,L., Sangiao-Alvarellos,S., Tovar,S., Raghay,K., Rodriguez-Cuenca,S., Deoliveira,R.M., Castaneda,T., Datta,R., Dong,J.Z., Culler,M., Sleeman,M.W., Alvarez,C.V., Gallego,R., Lelliott,C.J., Carling,D., Tschop,M.H., Dieguez,C., and Vidal-Puig,A. (2008). Hypothalamic fatty acid metabolism mediates the orexigenic action of ghrelin. Cell Metab 7, 389-399.
    Lernmark,A., Barmeier,H., Dube,S., Hagopian,W., Karlsen,A., and Wassmuth,R. (1991). Autoimmunity of diabetes. Endocrinol. Metab Clin. North Am. 20, 589-617.
    Levey,A.S., Coresh,J., Balk,E., Kausz,A.T., Levin,A., Steffes,M.W., Hogg,R.J., Perrone,R.D., Lau,J., and Eknoyan,G. (2003). National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann. Intern. Med. 139, 137-147.
    Liu,T., Huang,J.C., Lu,C.L., Yang,J.L., Hu,Z.Y., Gao,F., and Liu,Y.X. (2010). Immunization with a DNA vaccine of testis-specific sodium-hydrogen exchanger by oral feeding or nasal instillation reduces fertility in female mice. Fertil. Steril. 93, 1556-1566.
    Matsumoto,T., Kobayashi,T., Ishida,K., Taguchi,K., and Kamata,K. (2010). Enhancement of mesenteric artery contraction to 5-HT depends on Rho kinase and Src kinase pathways in the ob/ob mouse model of type 2 diabetes. Br. J. Pharmacol. 160, 1092-1104.
    Matsushita,M., Kuraya,M., Hamasaki,N., Tsujimura,M., Shiraki,H., and Fujita,T. (2002). Activation of the lectin complement pathway by H-ficolin (Hakata antigen). J. Immunol. 168, 3502-3506.
    Masters,J.R. (2002). HeLa cells 50 years on: the good, the bad and the ugly. Nat. Rev. Cancer 2, 315-319.
    Mehers,K.L. and Gillespie,K.M. (2008). The genetic basis for type 1 diabetes. Br. Med. Bull. 88, 115-129.
    Moneva,M.H. and Dagogo-Jack,S. (2002). Multiple drug targets in the management of type 2 diabetes. Curr. Drug Targets. 3, 203-221.
    Nagy,G., Kovacs-Nagy,R., Kereszturi,E., Somogyi,A., Szekely,A., Nemeth,N., Hosszufalusi,N., Panczel,P., Ronai,Z., and Sasvari-Szekely,M. (2009). Association of hypoxia inducible factor-1 alpha gene polymorphism with both type 1 and type 2 diabetes in a Caucasian (Hungarian) sample. BMC. Med. Genet. 10, 79.
    Nakaniwa,M., Hirayama,M., Shimizu,A., Sasaki,T., Asakawa,S., Shimizu,N., and Watabe,S. (2005). Genomic sequences encoding two types of medaka hemopexin-like protein Wap65, and their gene expression profiles in embryos. J. Exp. Biol. 208, 1915-1925.
    Neamat-Allah,M., Feeney,S.A., Savage,D.A., Maxwell,A.P., Hanson,R.L., Knowler,W.C., El Nahas,A.M., Plater,M.E., Shaw,J., Boulton,A.J., Duff,G.W., and Cox,A. (2001). Analysis of the association between diabetic nephropathy and polymorphisms in the aldose reductase gene in Type 1 and Type 2 diabetes mellitus. Diabet. Med. 18, 906-914.
    Newsholme,P., Haber,E.P., Hirabara,S.M., Rebelato,E.L., Procopio,J., Morgan,D., Oliveira-Emilio,H.C., Carpinelli,A.R., and Curi,R. (2007). Diabetes associated cell stress and dysfunction: role of mitochondrial and non-mitochondrial ROS production and activity. J. Physiol 583, 9-24.

    Oh,P.S. and Lim,K.T. (2008). Blocking of intracellular ROS production by phytoglycoprotein (30 kDa) causes anti-proliferation in bisphenol A-stimulated Chang liver cells. J. Appl. Toxicol. 28, 749-758.
    Peterson,P., Salmi,H., Hyoty,H., Miettinen,A., Ilonen,J., Reijonen,H., Knip,M., Akerblom,H.K., and Krohn,K. (1997). Steroid 21-hydroxylase autoantibodies in insulin-dependent diabetes mellitus. Childhood Diabetes in Finland (DiMe) Study Group. Clin. Immunol. Immunopathol. 82, 37-42.
    Rader,D.J. (2003). Regulation of reverse cholesterol transport and clinical implications. Am. J. Cardiol. 92, 42J-49J.
    Rahbar,S., Blumenfeld,O., and Ranney,H.M. (1969). Studies of an unusual hemoglobin in patients with diabetes mellitus. Biochem. Biophys. Res. Commun. 36, 838-843.
    Reiter,L.S., Kruithof,E.K., Cajot,J.F., and Sordat,B. (1993). The role of the urokinase receptor in extracellular matrix degradation by HT29 human colon carcinoma cells. Int. J. Cancer 53, 444-450.
    Rother,R.P., Bell,L., Hillmen,P., and Gladwin,M.T. (2005). The clinical sequelae of intravascular hemolysis and extracellular plasma hemoglobin: a novel mechanism of human disease. JAMA 293, 1653-1662.
    Rohrer,L., Hersberger,M., and von Eckardstein,A. (2004). High density lipoproteins in the intersection of diabetes mellitus, inflammation and cardiovascular disease. Curr. Opin. Lipidol. 15, 269-278.
    Shampo,M.A. and Kyle,R.A. (2006). John J. R. Macleod--Nobel prize for discovery of insulin. Mayo Clin. Proc. 81, 1006.
    Saso,L., Leone,M.G., Mo,M.Y., Grippa,E., Cheng,C.Y., and Silvestrini,B. (1999). Differential changes in alpha2-macroglobulin and hemopexin in brain and liver in response to acute inflammation. Biochemistry (Mosc. ) 64, 839-844.
    Sato,Y. (2006). [Vasohibin, a novel angiogenesis inhibitor ]. Seikagaku 78, 763-767.
    Shibuya,T., Watanabe,K., Yamashita,H., Shimizu,K., Miyashita,H., Abe,M., Moriya,T., Ohta,H., Sonoda,H., Shimosegawa,T., Tabayashi,K., and Sato,Y. (2006). Isolation and characterization of vasohibin-2 as a homologue of VEGF-inducible endothelium-derived angiogenesis inhibitor vasohibin. Arterioscler. Thromb. Vasc. Biol. 26, 1051-1057.
    Shimizu,K., Watanabe,K., Yamashita,H., Abe,M., Yoshimatsu,H., Ohta,H., Sonoda,H., and Sato,Y. (2005). Gene regulation of a novel angiogenesis inhibitor, vasohibin, in endothelial cells. Biochem. Biophys. Res. Commun. 327, 700-706.
    Smith,A., Eskew,J.D., Borza,C.M., Pendrak,M., and Hunt,R.C. (1997). Role of heme-hemopexin in human T-lymphocyte proliferation. Exp. Cell Res. 232, 246-254.
    Takahashi,N., Takahashi,Y., and Putnam,F.W. (1985). Complete amino acid sequence of human hemopexin, the heme-binding protein of serum. Proc. Natl. Acad. Sci. U. S. A 82, 73-77.
    Shipulina,N., Smith,A., and Morgan,W.T. (2000). Heme binding by hemopexin: evidence for multiple modes of binding and functional implications. J. Protein Chem. 19, 239-248.
    Takahashi,N., Takahashi,Y., and Putnam,F.W. (1985). Complete amino acid sequence of human hemopexin, the heme-binding protein of serum. Proc. Natl. Acad. Sci. U. S. A 82, 73-77.
    Tattersall,R. (1997). Frederick Pavy (1829-1911) and his opposition to the glycogenic theory of Claude Bernard. Ann. Sci. 54, 361-374.
    Tan,F., Lu,L., Cai,Y., Wang,J., Xie,Y., Wang,L., Gong,Y., Xu,B.E., Wu,J., Luo,Y., Qiang,B., Yuan,J., Sun,X., and Peng,X. (2008). Proteomic analysis of ubiquitinated proteins in normal hepatocyte cell line Chang liver cells. Proteomics. 8, 2885-2896.
    Trobridge,G.D., Wu,R.A., Beard,B.C., Chiu,S.Y., Munoz,N.M., von Laer,D., Rossi,J.J., and Kiem,H.P. (2009). Protection of stem cell-derived lymphocytes in a primate AIDS gene therapy model after in vivo selection. PLoS. One. 4, e7693.
    Tolosano,E. and Altruda,F. (2002). Hemopexin: structure, function, and regulation. DNA Cell Biol. 21, 297-306.
    Wang,W., Hino,N., Yamasaki,H., Aoki,T., and Ochi,R. (2002). KV2.1 K+ channels underlie major voltage-gated K+ outward current in H9c2 myoblasts. Jpn. J. Physiol 52, 507-514.
    Wong,M.C., Chung,J.W., and Wong,T.K. (2007). Effects of treatments for symptoms of painful diabetic neuropathy: systematic review. BMJ 335, 87.
    Zhang,B.B., Zhou,G., and Li,C. (2009). AMPK: an emerging drug target for diabetes and the metabolic syndrome. Cell Metab 9, 407-416.
    http://home.chgh.org.tw/chgh/info2_info.jspx?id=402883aa2c2a2975012c2a766015000c

    無法下載圖示 全文公開日期 本全文未授權公開 (校內網路)
    全文公開日期 本全文未授權公開 (校外網路)

    QR CODE