精氨酸酶Ⅱ:一种“不同寻常”的酶

Arginase Ⅱ:An extraordinary enzyme

精氨酸酶Ⅱ起源于早期生命形式。它将L-精氨酸转化为尿素和鸟氨酸,从而维持机体的各种生理功能。机体精氨酸酶Ⅱ水平增加导致心血管疾病与某些慢性炎症疾病的发生,导致这些疾病发生可能有四个原因:第一,过多的精氨酸酶Ⅱ与一氧化氮合酶竞争L-精氨酸从而降低NO的产生;第二,生成过多的鸟氨酸会导致血管结构改变和神经毒性;第三,精氨酸酶Ⅱ参与某些炎性反应的信号通路,最终导致炎症的发生;第四,精氨酸酶Ⅱ可以促使巨噬细胞产生炎症反应(具有M1型表型)。本文综述了近年来精氨酸酶Ⅱ在心血管疾病和巨噬细胞中的作用以及与氧化应激和炎症相关的机制,为临床靶向精氨酸酶Ⅱ治疗疾病提供理论依据。

Arginase Ⅱhas evolved from ancestral genes in early life forms.It converts L-arginine to urea and ornithine to maintain physiology.Excessive arginase Ⅱ activity in mammals is associated with cardiovascular and chronic inflammation diseases.Four aspects of this elevated activity may be involved in these disease states.First,excessive arginase Ⅱ activity reduces the supply of L-arginine needed by nitric oxide(NO)synthase to produce NO.Second,excessive production of ornithine leads to disrupted vascular structure and neural toxicity.Third,arginase Ⅱ over-activity in certain signaling pathways leads to increased inflammation.Forth,arginase Ⅱpromotes the macrophage inflammatory response(M1 macrophage).Here,we review the role of arginase Ⅱin cardiovascular diseases and macrophages and in oxidative stress and inflammation mechanisms.We also discuss targeting arginase Ⅱas a promising therapeutic strategy.