丹皮酚与钙粘素相互作用的分析研究
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摘要
丹皮酚对多种肿瘤细胞具有抑制作用,而钙粘素是与肿瘤产生和恶化密切相关的一类糖蛋白。本研究运用荧光光谱法和原子力显微技术探索了丹皮酚与钙粘素的相互作用。荧光光谱法研究结果表明,丹皮酚对钙粘素的荧光具有显著的猝灭作用,通过猝灭常数随温度变化趋势推断为静态猝灭过程。丹皮酚与钙粘素形成复合物的热力学参数分别为ΔH=-4.3×10~5J/mol和ΔS=-1.3×10~3J/(mol·K),表明此结合过程以氢键和范德华力为主。原子力显微观察结果表明,钙粘素分子间可形成有序长链结构,丹皮酚加入后能显著破坏这种组装结构而形成短链结构,这是由于丹皮酚与钙粘素末端色氨酸残基的作用而影响相邻钙粘素分子结构域间的交错作用所致。本研究结果表明,钙粘素可能是丹皮酚体现其活性的一个重要作用靶点。
Paeonol has inhibitory effect on a variety of tumor cells,whereas cadherin is a kind of glycoprotein that is associated with the occurrence and development of different tumor. In this study,the interactions of paeonol and E-cadherin have been investigated by fluorescence spectrometry and atomic force microscopy( AFM).Fluorescence spectrometry results revealed that the addition of paeonol significantly quenched the fluorescence of E-cadherin. Based on the results of the quenching constant,it was inferred that the interaction of paeonol and E-cadherin was a static quenching process. The thermodynamic parameters ΔH and ΔS were calculated to be -4.3×10~5J/mol and -1.3×10~3J/(mol·K),respectively,which proved the involvement of weak interactive forces such as hydrogen bond van der Waals force. AFM results revealed that cadherin molecules were assembled into the long-chain structure. The addition of paeonol could significantly disrupt these assembling structures into short chains,which could be ascribed to the damage of the interdigitation model from the adjacent cadherin molecules. All these results reveal that cadherin is an important target of paeonol to modulate its activity.
Paeonol has inhibitory effect on a variety of tumor cells,whereas cadherin is a kind of glycoprotein that is associated with the occurrence and development of different tumor. In this study,the interactions of paeonol and E-cadherin have been investigated by fluorescence spectrometry and atomic force microscopy( AFM).Fluorescence spectrometry results revealed that the addition of paeonol significantly quenched the fluorescence of E-cadherin. Based on the results of the quenching constant,it was inferred that the interaction of paeonol and E-cadherin was a static quenching process. The thermodynamic parameters ΔH and ΔS were calculated to be -4.3×10~5J/mol and -1.3×10~3J/(mol·K),respectively,which proved the involvement of weak interactive forces such as hydrogen bond van der Waals force. AFM results revealed that cadherin molecules were assembled into the long-chain structure. The addition of paeonol could significantly disrupt these assembling structures into short chains,which could be ascribed to the damage of the interdigitation model from the adjacent cadherin molecules. All these results reveal that cadherin is an important target of paeonol to modulate its activity.
引文
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3 Yang S,Wang X,Zhong G.Int.J.Clin.Exp.Med.,2016,9(7):13900-13908
4 Wu J,Xue X,Zhang B,Cao H,Kong F,Jiang W,Li J,Sun D,Guo R.Tumor.Biol.,2016,37(9):12301-12313
5 LEI Gen-Hu,LIU Li-Ting,DAI Xiao-Jun,WEI Yin-Mao,GONG Bo-Lin.Acta Chimica Sinica,2010,68(1):55-61雷根虎,刘丽亭,戴小军,卫引茂,龚波林.化学学报,2010,68(1):55-61
6 Pokutta S,Weis W I.Annu.Rev.Cell Dev.Biol.,2007,23(23):237-261
7 Guilford P,Hopkins J,Harraway J,Mc Leod M,Mc Leod N,Harawira P,Taite H,Scoular R,Miller A,Reeve A E.Nature,1998,392(6674):402-405
8 Perl A,Wilgenbus P,Dahl U,Semb H,Christofori G.Nature,1998,392(6672):190-193
9 Grieve A G,Rabouille C.J.Cell Sci.,2014,127(15):3331-3346
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11 Hu Q P,Kuang J Y,Yang Q K,Bian X W,Yu S C.Int.J.Cancer,2016,138(12):2804-2812
12 Patil P U,D'Ambrosio J,Inge L J,Mason R W,Rajasekaran A K.J.Cell Sci.,2015,128(23):4366-4379
13 Wang J.J.Biochem.Mol.Toxicol.,2015,29(5):213-220
14 Hu S,Liu K,Li Y,Ding Q,Peng W,Chen M.Can.J.Chem.,2014,92(92):274-278
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21 Boggon T J,Murray J,Chappuis-Flament S,Wong E,Gumbiner B M,Shapiro L.Science,2002,296(5571):1308-1313
22 Li Y,Altorelli N L,Bahna F,Honig B,Shapiro L,Palmer A G.Proc.Natl.Acad.Sci.USA,2013,110(41):16462-16467
23 He W,Cowin P,Stokes D L.Science,2003,302(5642):109-113