镉诱导细胞自噬的分子机制研究进展

Advance in molecular mechanism of autophagy induced by cadmium

镉是一种常见的环境污染物。高剂量的镉暴露引起细胞凋亡,近来有研究表明镉暴露能够引起细胞自噬。自噬是真核生物中进化上高度保守的过程,用来降解和回收利用生物大分子和受损细胞器,对个体的正常发育和应对环境刺激非常重要,自噬调控障碍与机体的许多生理和病理过程相关,如神经退行性疾病、癌症、病原微生物感染等。镉诱导细胞自噬的分子机制涉及许多细胞内信号通路,镉暴露会导致细胞产生氧化压力(reactive oxygen species,ROS),激活肝激酶B1-AMP激活的蛋白激酶(liver kinase B1-AMP-activated protein kinase,LKB1-AMPK)信号通路引起细胞自噬的发生;镉可以通过细胞质钙离子的增加激活钙调素依赖蛋白激酶引起自噬的发生;镉还会通过内质网氧化压力诱导细胞自噬的发生。大量研究表明镉诱导的细胞自噬与细胞死亡有关,也有一些研究认为自噬可以作为一种保护机制抑制镉引发的细胞死亡。尽管镉诱导自噬的研究已经有了一些进展,但完整的分子机制还不是非常清楚。

Cadmium is a common environmental pollutant,which causes cell apoptosis. Recently,some researches have shown low levels of cadmium exposure could cause cell autophagy. Autophagy,an evolutionarily conserved mechanism for sequestering and degrading long-lived cellular proteins and damaged organelles,is important in normal development and serve as a response to changing environmental stimuli. Its alteration is associated with many physiological and pathological process of the body,such as neurodegenerative diseases,cancer,pathogenic microorganism infection. The molecular mechanism of autophagy induced by cadmium is involved in many signal pathways,which can be induced by the generation of reactive oxygen species（ ROS） and to activate liver kinase B1-AMP-activated protein kinase（ LKB1- AMPK） signaling pathway,or a rapid elevation in cytosolic calcium to activate calmodulin-dependent protein kinase. Autophagy can also be induced by ER stress. Numerous studies show that autophagy induced by cadmium plays an important role in cell death,while other studies indicate that autophagy can serve as a protective mechanism against cadmium caused cell death. Although the cadmium induced autophagy has been investigated intensively,the underlying mechanisms are not yet completely understood. The purpose of this review was to elaborate the molecular mechanism of autophagy induced by cadmium.