Prostaglandins are a diverse family of biological active molecules that are synthesized after liberation of arachnidonic or linolenic acid from the plasma membrane by phospholipase A2 (PLA2). Specific prostaglandins may be pro-inflammatory or anti-inflammatory due to a poorly understood biochemical equilibrium. Some of the anti-inflammatory prostaglandins namely, prostaglandin A1 (PGA1) and prostaglandin E1 (PGE1) have a cyclopentenone moiety that can react and modify a protein’s activity. These two prostaglandins are electrophilic reactive lipid species and are formed as a result of the reaction cascade initiated by PLA2. It was of interest to study the interaction with these prostaglandins as they could either amplify or block this enzyme’s activity. We found that the former is true initially as there is a shorter time to activate the protein on the lipid membrane and an overall increase in hydrolysis was observed when PGA1 and PGE1 prostaglandin was added with PLA2 and liposomes. The interfacial activation model was further explored in which there is a modification of the enzyme rather than a modifcation of the substrate. However, after a time the protein was shown to form amyloid like fibrils thereby blocking further hydrolysis. The fibrillization kinetics in the presence of the one of the prostaglandins was monitored using thioflavin T (ThT) and the resulting fibrils were characterized using transmission electron microscopy (TEM) and atomic force microscopy (AFM). Modification of PLA2 by these prostaglandins leading to amyloid like fibrils gives an additional perspective of control of the interfacial activation mechanism of this enzyme.

前列腺素是一个多样化的生物活性分子家族，在磷脂酶 A2 (PLA2) 从质膜释放花生四烯酸或亚麻酸后合成。由于对生化平衡知之甚少，特定的前列腺素可能是促炎或抗炎的。一些抗炎前列腺素，即前列腺素 A1 (PGA1) 和前列腺素 E1 (PGE1) 具有可以反应和改变蛋白质活性的环戊烯酮部分。这两种前列腺素是亲电活性脂质物质，是由 PLA2 引发的反应级联反应的结果。研究与这些前列腺素的相互作用很有趣，因为它们可以放大或阻断这种酶的活性。我们发现前者最初是正确的，因为激活脂质膜上的蛋白质的时间较短，并且当 PGA1 和 PGE1 前列腺素与 PLA2 和脂质体一起加入时，观察到水解的总体增加。进一步探索了界面活化模型，其中存在酶的修饰而不是底物的修饰。然而，一段时间后，蛋白质显示形成淀粉样原纤维，从而阻止进一步水解。使用硫代黄素 T (ThT) 监测在前列腺素之一存在下的原纤维化动力学，并使用透射电子显微镜 (TEM) 和原子力显微镜 (AFM) 表征所得原纤维。