胞红蛋白在调控细胞铁死亡中的作用

Role of Cytoglobin in Ferroptosis Regulation

近年来,以细胞内氧化还原平衡失调为重要诱因,具有铁依赖性和以脂质过氧化物堆积引起细胞膜损伤为主要特征的细胞铁死亡备受关注。越来越多的研究表明,细胞铁死亡在疾病发生及防治方面具有重要作用。胞红蛋白(cytoglobin,CYGB),又名星状细胞激活蛋白(stellate cell activating protein,STAP),是一种珠蛋白,不仅能可逆地结合氧分子,储存和传递氧气,同时在其氨基酸序列中含2个半胱氨酸残基,可形成分子内部的二硫键,在感受细胞内氧化还原状态变动时,改变自身空间结构,引起生物活性及下游信号通路的变化。同时,CYGB还具有一氧化氮双加氧酶活性,能够清除过量一氧化氮与活性氧物质超氧阴离子反应生成的有毒ONOO~-,防止其对线粒体功能的破坏。而细胞内活氧物质和线粒体是影响细胞铁死亡的重要因素。因此,本综述主要围绕CYGB清除活性氧物质及调控一氧化氮代谢等的作用机制,并结合我们最近有关CYGB通过p53-YAP1轴调控细胞内脂质代谢的研究进行阐述,提出CYGB通过参与细胞铁死亡调控来行使功能,为心血管功能,肝纤维化及癌症发生等相关疾病的预防和治疗提供重要的理论依据。

Ferroptosis is a recently reported iron-dependent cell death,which is induced by the broken of cellular redox homeostasis and characterized by high level of lipid peroxide.More and more studies have indicated the importance of ferroptosis during disease development and prevention.As a member of globin family,cytoglobin(CYGB),also known as stellate cell activating protein(STAP),can bind to oxygen for its transportation.Moreover,CYGB contains two cysteins within its amino acid sequence and could form the S-S bond when there has change of cellular redox which will result in downstream signaling alternation.Furthermore,CYGB has nitric oxygen dioxygenase activity to scavenge excessive nitric oxygen and prevent the production of ONOO^(-)for the damage to mitochondrial function.It is well known that alternations of cellular redox homeostasis and mitochondrial function contribute greatly to ferroptosis.Here,we gave an introduction of the recent research of CYGB in vascular function,liver fibrosis,and cancers.The important role of CYGB and related signaling pathways in regulating nitric oxide metabolism and cellular redox homeostasis was also summarized.Furthermore,based on our latest research which demonstrated that CYGB regulated the reactive oxygen species and lipid peroxides through p53-YAP1 axis,we proposed that CYGB is an important factor to regulate cellular redox homeostasis and ferroptosis.Thus,it would be of great importance to explore the molecular mechanism of CYGB in ferroptosis regulation,which will give a further understanding of CYGB function and its significance in disease prevention and therapy.