Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan.
Free Radic Res. 2011 Oct;45(10):1196-206. doi: 10.3109/10715762.2011.606814. Epub 2011 Aug 16.
Endogenous S-nitrosated human serum albumin (E-Mono-SNO-HSA) is a large molecular weight nitric oxide (NO) carrier in human plasma, which has shown many beneficial effects in different animal models. To construct more efficient SNO-HSA preparations, SNO-HSA with many conjugated SNO groups has been prepared using chemical modification (CM-Poly-SNO-HSA). We have compared the properties of such a preparation to those of E-Mono-SNO-HSA. Cellular uptake of NO from E-Mono-SNO-HSA partly takes place via low molecular weight thiol, and it results in cytoprotective effects by induction of heme oxygenase-1. By contrast, transfer of NO from CM-Poly-SNO-HSA into the cells is faster and more pronounced. The influx mainly takes place by cell-surface protein disulfide isomerase. The considerable NO inflow results in apoptotic cell death by ROS induction and caspase-3 activation. Thus, increasing the number of SNO groups on HSA does not simply intensify the cellular responses to the product but can also result in very different effects.
内源性 S-亚硝基化人血清白蛋白 (E-Mono-SNO-HSA) 是人血浆中一种大分子量的一氧化氮 (NO) 载体，在不同的动物模型中表现出许多有益的作用。为了构建更有效的 SNO-HSA 制剂，我们使用化学修饰 (CM-Poly-SNO-HSA) 制备了具有多个共轭 SNO 基团的 SNO-HSA。我们比较了这种制剂与 E-Mono-SNO-HSA 的性质。E-Mono-SNO-HSA 中 NO 的细胞摄取部分通过低分子量巯基发生，通过诱导血红素加氧酶-1 产生细胞保护作用。相比之下，CM-Poly-SNO-HSA 中 NO 的转移进入细胞更快、更明显。这种转移主要通过细胞表面蛋白二硫键异构酶发生。大量的 NO 流入通过诱导 ROS 和 caspase-3 激活导致细胞凋亡死亡。因此，增加 HSA 上 SNO 基团的数量并不会简单地增强细胞对产物的反应，还可能导致非常不同的效果。
