Ciolkowski Michal, Rozanek Monika, Szewczyk Michal, Klajnert Barbara, Bryszewska Maria
Department of General Biophysics, University of Lodz, Lodz, Poland.
Biochim Biophys Acta. 2011 Nov;1808(11):2714-23. doi: 10.1016/j.bbamem.2011.07.021. Epub 2011 Jul 23.
Dendrimers are a relatively new and still not fully examined group of polybranched polymers. In this study polyamidoamine dendrimers with hydroxyl surface groups (PAMAM-OH) of third, fourth and fifth generation (G3, G4 and G5) were examined for their ability to influence the activity of human erythrocyte plasma membrane adenosinetriphosphatases (ATPases). Plasma membrane ATPases are a group of enzymes related, among others, to the maintenance of ionic balance inside the cell. An inhibition of their activity may result in a disturbance of cell functioning. Two of examined dendrimers (G4 and G5) were found to inhibit the activity of Na(+)/K(+) ATPase and Ca(2+) ATPase by 20-30%. The observed effect was diminished when higher concentrations of dendrimers were used. The experiment with the use of pyrene as fluorescent probe sensitive to the changes in microenvironment's polarity revealed that it was an effect of dendrimers' self-aggregation. Additional studies showed that PAMAM-OH dendrimers were able to decrease the fluidity of human erythrocytes plasma membrane. Obtained results suggest that change in plasma membrane fluidity was not caused by the dendrimer-lipid interaction, but dendrimer-protein interaction. Different pattern of influence of dendrimers on ATPases activity and erythrocyte membrane fluidity suggests that observed change in ATPases activity is not a result of dendrimer-lipid interaction, but may be related to direct interaction between dendrimers and ATPases.
树枝状大分子是一类相对较新且尚未得到充分研究的多支链聚合物。在本研究中，对具有羟基表面基团的第三代、第四代和第五代聚酰胺-胺树枝状大分子（PAMAM-OH，即G3、G4和G5）影响人红细胞质膜腺苷三磷酸酶（ATP酶）活性的能力进行了研究。质膜ATP酶是一类与维持细胞内离子平衡等相关的酶。其活性受到抑制可能会导致细胞功能紊乱。在所研究的树枝状大分子中，发现其中两种（G4和G5）可使Na(+)/K(+)ATP酶和Ca(2+)ATP酶的活性抑制20%-30%。当使用更高浓度的树枝状大分子时，所观察到的这种效应会减弱。使用芘作为对微环境极性变化敏感的荧光探针进行的实验表明，这是树枝状大分子自聚集的结果。进一步的研究表明，PAMAM-OH树枝状大分子能够降低人红细胞质膜的流动性。所得结果表明，质膜流动性的变化不是由树枝状大分子与脂质的相互作用引起的，而是由树枝状大分子与蛋白质的相互作用引起的。树枝状大分子对ATP酶活性和红细胞膜流动性的影响模式不同，这表明所观察到的ATP酶活性变化不是树枝状大分子与脂质相互作用的结果，而可能与树枝状大分子和ATP酶之间的直接相互作用有关。
