聚乙烯亚胺修饰的氧化石墨烯对人胰岛淀粉样蛋白聚集的抑制作用

doi:10.7503/cjcu20180166

摘要/Abstract

摘要：

利用共价结合的方法在氧化石墨烯(GO)表面修饰聚乙烯亚胺(PEI), 得到了稳定的GO-PEI复合物. 透射电子显微镜和圆二色谱实验结果显示, 对于人类胰岛淀粉样多肽(hIAPP)的纤维化聚集GO-PEI比GO有更强的抑制能力. 结合ThT荧光和原子力显微镜实验结果发现, 在hIAPP聚集过程的成核初期加入GO-PEI有最好的抑制效果, 在纤维化过程的生长期加入GO-PEI能部分抑制hIAPP纤维的形成, 但GO-PEI不能使成熟的hIAPP纤维解聚集.

关键词: 氧化石墨烯, 人胰岛淀粉样多肽, 抑制剂

Abstract:

Preventing human islet amyloid polypeptide(hIAPP) fibrillogenesis has been a primary strategy in development of therapeutic drugs for type Ⅱ diabetes. In this study, we prepared stable GO-PEI complex by modification of polyetherimide(PEI) on the surface of graphene oxide(GO) using covalent binding method. The results of transmission electron microscopy(TEM) and circular dichroism(CD) show that GO-PEI is more efficient than GO in inhibiting hIAPP fibril formation. The ThT fluorescence assay and atomic force microscopy(AFM) image data show that GO-PEI is the most effective for the inhibition of hIAPP fibrillation when it is added at the initial stage of hIAPP aggregation, and less effective when added in the growing period of hIAPP aggregation, but the inhibitor disables to disrupt the matured hIAPP fibrils. The findings may provide information valuable to the research and development of GO-based inhibitors.

Key words: Graphene oxide, Human islet amyloid polypeptide, Inhibitor

中图分类号:

O631
O641.3

TrendMD:

陆通, 王春洋, 朱智慧, 蒋巍, 霍明楠, 李菲. 聚乙烯亚胺修饰的氧化石墨烯对人胰岛淀粉样蛋白聚集的抑制作用. 高等学校化学学报, 2018, 39(6): 1274.

LU Tong, WANG Chunyang, ZHU Zhihui, JIANG Wei, HUO Mingnan, LI Fei. Polyethyleneimine Functionalized Graphene Oxide Against hIAPP Amyloid Aggregation^†. Chem. J. Chinese Universities, 2018, 39(6): 1274.

图/表 8

Fig.1 IR(A) and TGA(B) spectra of GO(a), GO-PEI(b) and PEI(c)

Fig.2 AFM images of GO(A) and GO-PEI(B)

Fig.3 Kinetics of hIAPP aggregation as monitored by the thioflavin T fluorescence(A) and far-UV CD spectra of hIAPP in the absence(a) and presence of GO(b) and GO-PEI(c)(B)

Fig.4 TEM images of hIAPP(A), hIAPP with GO(B) and GO-PEI(C)

Fig.5 Kinetics of hIAPP aggregation as monitored by the thioflavin T fluorescence(A) in the absence(a) and presence of PEI(b) and TEM image(B) of hIAPP in the presence of PEI

Table 1 Hydrodynamic diameter and Zeta potential of GO and GO-PEI

Sample	Diameter(DLS)/nm	Zeta potential/mV
GO	200—600	-10.5
GO-PEI	150—300	50.1

Fig.6 Aggregation process of hIAPP modulated by GO-PEI at various time

Fig.7 AFM images of hIAPP(A) and mixed with GO-PEI at the incubation time of 0 h(B), 5 h(C) and 8 h(D)All images were recorded after the mixtures were further incubated for 10 h.

参考文献 47

[1]	Soto C., FEBS Lett., 2001, 498, 204—207
[2]	Soto C., Nat. Rev. Neurosci., 2003, 4, 49—60
[3]	Chiti F., Dobson C .M., Annu. Rev. Biochem., 2006, 75, 333—366
[4]	Westermark P., Andersson A., Westermark G.T., Physiological Reviews, 2011, 91, 795—826
[5]	Kahn S. E., Andrikopoulos S., Verchere C. B., Diabetes, 1999, 48, 241—253
[6]	Lorenzo A., Razzaboni B., Weir G. C., Yankner B. A., Nature, 1994, 368, 756—760
[7]	Brender J. R., Salamekh S., Ramamoorthy A., Accounts of Chemical Research, 2011, 4, 454—462
[8]	Westermark P., Wernstedt C., Wilander E., Hayden D. W., O’Brien T. D., Johnson K. H., Proc. Natl. Acad. Sci. USA, 1987, 84, 3881—3885
[9]	De Toma A. S., Salamekh S., Ramamoorthy A., Lim M. H., Chemical Society Reviews, 2012, 41, 608—621
[10]	Pithadia A. S., Bhunia A., Sribalan R., Padmini V., Fierke C. A., Ramamoorthy A., Chem. Commun., 2016, 52, 942—945
[11]	Cheng B., Gong H., Li X., Sun Y., Zhang X., Chen H., Liu X., Zheng L., Huang K., Biochem. Biophys. Res.Commun., 2012, 419, 495—499
[12]	Wang L., Lei L., Li Y., Wang L., Li F., FEBS Lett., 2014, 588, 884—891
[13]	Tatarek-Nossol M., Yan L. M., Schmauder A., Tenidis K., Westermark G., Kapurniotu A., Chem. Biol., 2005, 12, 797—809
[14]	Yan L. M., Tatarek-Nossol M., Velkova A., Kazantzis A., Kapurniotu A., Proceedings of the National Academy of Sciences of the United States of America, 2006, 103, 2046—2051
[15]	Wang L., Zhu S. J., Lu T., Zhang G. J., Xu J., Song Y. B., Li Y., Wang L. P., Yang B., Li F., J. Mater. Chem. B, 2016, 4, 4913—4921
[16]	Liu G., Men P., Kudo W., Perry G., Smith M.A., Neuroscience Letters, 2009, 455, 187—190
[17]	Kong B., Zhu A., Ding C., Zhao X., Li B., Tian Y., Advanced Materials, 2012, 24, 5844—5848
[18]	Welsher K., Liu Z., Sherlock S. P., Robinson J. T., Chen Z., Daranciang D., Dai H., Nat. Nanotechnol., 2009, 4, 773—780
[19]	Jeong J., Cho M., Lim Y. T., Song N. W., Chung B. H., Angewandte Chemie International Edition, 2009, 48, 5296—5299
[20]	Zhu S., Zhang J., Tang S., Qiao C., Wang L., Wang H., Liu X., Li B., Li Y., Yu W., Wang X., Sun H., Yang B., Advanced Functional Materials, 2012, 22, 4732—4740
[21]	Georgakilas V., Tiwari J. N., Kemp K. C., Perman J. A., Bourlinos A. B., Kim K. S., Zboril R., Chem. Rev., 2016, 116, 5464—5519
[22]	Wang C., Wang X., Lu T., Liu F., Guo B., Wen N., Du Y., Lin H., Tang J., Zhang L., RSC Adv., 2016, 6, 22461—22468
[23]	Mahmoudi M ., Akhavan O., Ghavami M., Rezaee F., Ghiasi S.M. A., Nanoscale, 2012, 4, 7322—7325
[24]	Li M., Yang X. J., Ren J. S., Qu K. G., Qu X. G., Adv. Mater., 2012, 24, 1722—1728
[25]	Li Q., Liu L., Zhang S., Xu M., Wang X., Wang C., Besenbacher F., Dong M., Chem. Eur. J., 2014, 20, 7236—7240
[26]	Liu Y., Xu L., Dai W., Dong H., Wen Y., Zhang X., Nanoscale, 2015, 7, 19060—19065
[27]	Nedumpully-Govindan P., Gurzov E. N., Chen P., Pilkington E. H., Stanley W. J., Litwak S. A., Davis T. P., Ke P. C., Ding F., Physical Chemistry Chemical Physics, 2016, 18, 94—100
[28]	Liu J., Yang Z., Li H., Gu Z., Garate J. A., Zhou R., J. Chem. Phys., 2014, 141, 22D520
[29]	Lin C. Y., Cheng Y. S., Liao T. Y., Lin C., Chen Z. T., Twu W. I., Wang C. W., Tan D. T., Liu R. S., Tu P., Chen R. P. Y., Journal of Alzheimer’s Disease, 2016, 53, 1053—1067
[30]	Georgieva J. V., Kalicharan D., Couraud P. O., Romero I. A., Weksler B., Hoekstra D., Zuhorn I. S., Molecular Therapy, 2011, 19, 318—325
[31]	Loftus L. T., Li H. F., Gray A. J., Hirata-Fukae C., Stoica B. A., Futami J., Yamada H., Aisen P. S., Matsuoka Y., Neuroscience, 2006, 139, 1061—1067
[32]	Futami J., Kitazoe M., Maeda T., Nukui E., Sakaguchi M., Kosaka J., Miyazaki M., Kosaka M., Tada H., Seno M., Sasaki J., Huh N. H., Namba M., Yamada H., J. Biosci. Bioeng., 2005, 99, 95—103
[33]	Murata H., Futami J., Kitazoe M., Kosaka M., Tada H., Seno M., Yamada H., J. Biosci. Bioeng., 2008, 105, 34—38
[34]	O’Connor D. M., Boulis N. M., Trends in Molecular Medicine, 2015, 21, 504—512
[35]	Hudry E., Van Da D., Kulik W., De Deyn P. P., Stet F. S., Ahouansou O., Benraiss A., Delacourte A., Bougnères P., Aubourg P., Cartier N., Molecular Therapy, 2010, 18, 44—53
[36]	Morton G. J., Niswender K. D., Rhodes C. J., Myers M. G., Blevins J. E., Baskin D. G., Schwartz M. W., Endocrinology, 2003, 144, 2016—2024
[37]	Zhang L., Lu Z., Zhao Q., Huang J., Shen H., Zhang Z., Small, 2011, 7, 460—464
[38]	Feng L., Zhang S., Liu Z., Nanoscale, 2011, 3, 1252—1257
[39]	Chen B., Liu M., Zhang L., Huang J., Yao J., Zhang Z., J. Mater. Chem., 2011, 21, 7736—7741
[40]	Hummers W. S., Offeman R. E., J. Am. Chem. Soc., 1958, 80, 1339
[41]	Biancalana M., Koide S., Biochim. Biophys. Acta, 2010, 1804, 1405—1412
[42]	Batzli K. M., Love B. J., Materials Science and Engineering: C, 2015, 48, 359—364
[43]	Jaikaran E. T. A. S., Higham C. E., Serpell L. C., Zurdo J., Gross M., Clark A., Fraser P. E., FEBS Letters, 2001, 308, 515—525
[44]	Higham C. E., Jaikaran E. T. A. S., Fraser P. E., Gross M., Clark A., FEBS Letters, 2000, 470, 55—60
[45]	Ferreira S. T., Vieira M. N. N., De Felice F. G., IUMB Life, 2007, 59, 332—345
[46]	Hardy J., Selkoe D.J., Science, 2002, 297, 353—356
[47]	Glabe C. G., Kayed R., Neurology, 2006, 66(Suppl.), S74—S78