Instituto Superior de Investigaciones Biológicas (INSIBIO), CONICET-UNT, Instituto de Química Biológica "Dr. Bernabe Bloj", Facultad de Bioquímica, Química y Farmacia, UNT, Tucumán, Argentina.
Instituto Superior de Investigaciones Biológicas (INSIBIO), CONICET-UNT, Instituto de Química Biológica "Dr. Bernabe Bloj", Facultad de Bioquímica, Química y Farmacia, UNT, Tucumán, Argentina.
Biochim Biophys Acta Biomembr. 2019 Jan;1861(1):170-177. doi: 10.1016/j.bbamem.2018.08.002. Epub 2018 Aug 11.
In the present work, we analyzed how external factors can modulate the efficiency of epigallocatechin‑3‑O‑gallate (EGCG) inhibition of a membrane-bound isoform of the acetylcholinesterase. Increasing the ionic strength but not the osmolarity of the bulk medium proved to be an important factor. In addition, we verified a clear correlation between the inhibitory activity with the order degree of the membranes by using cholesterol-partially depleted red blood cell ghosts. These two factors i.e. high salt concentration in the bulk medium and less viscous membranes, allow a deeper insertion of the EGCG into the lipid bilayer, thus leading to a greater inhibition of AChE. As a corollary, we propose that any treatment or process that leads to a slight decrease in cholesterol content in the membranes can efficiently enhance the inhibitory activity of EGCG, which can have important consequences in all the pathologies where the inhibition of AChE is recommended.
在本工作中，我们分析了外部因素如何调节表没食子儿茶素没食子酸酯（EGCG）抑制膜结合型乙酰胆碱酯酶的效率。结果证明，增加离子强度而不是渗透压是一个重要因素。此外，我们使用胆固醇部分耗尽的红细胞胞 ghosts 验证了抑制活性与膜有序度之间的明显相关性。这两个因素，即介质中的高盐浓度和较低粘性的膜，允许 EGCG 更深地插入脂质双层，从而导致对 AChE 的更大抑制。因此，我们提出任何导致膜中胆固醇含量略有下降的治疗或处理都可以有效地增强 EGCG 的抑制活性，这在所有推荐抑制 AChE 的病理学中都可能产生重要后果。
