title: The downregulation of thioredoxin accelerated Neuro2a cell apoptosis induced by advanced glycation end product via activating several pathways.
abstract: Thioredoxin (Trx), a 12 kDa protein, has different functions in different cellular environments, playing important anti-oxidative and anti-apoptotic roles and regulating the expression of transcription factors. Advanced glycation end products (AGEs) are a heterogeneous group of irreversible adducts from glucose-protein condensation reactions and are considered crucial to the development of diabetic nephropathy, retinopathy, neurodegeneration and atherosclerosis. The aim of this study was to use a Trx inhibitor to investigate the effects and mechanism of Trx down-regulation on AGE-induced Neuro2a cell apoptosis. Neuro2a cells were cultured in vitro and treated with different conditions. The apoptosis and proliferation of Neuro2a cells were detected using flow cytometry, DNA-Ladder and CCK8 assays. Rho 123 was used to detect the mitochondrial membrane potential. ROS generation and caspase3 activity were detected using a DCFH-DA probe and micro-plate reader. Western blotting and real-time PCR were used to detect the expression of proteins and genes. We found that the down-regulation of thioredoxin could accelerate AGE-induced apoptosis in Neuro2a cells. A possible underlying mechanism is that the down-regulation of thioredoxin stimulated the up-regulation of ASK1, p-JNK, PTEN, and Txnip, as well as the down-regulation of p-AKT, ultimately increasing ROS levels and caspase3 activity.
authors.affiliation: Department of Histology and Embryology, Dalian Medical University, Dalian 116044, LiaoNing Province, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Ren
authors.affiliation: Department of Histology and Embryology, Dalian Medical University, Dalian 116044, LiaoNing Province, China.
authors.forename: Haiying
authors.initials: H
authors.lastname: Ma
authors.affiliation: Department of Histology and Embryology, Dalian Medical University, Dalian 116044, LiaoNing Province, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Department of Histology and Embryology, Dalian Medical University, Dalian 116044, LiaoNing Province, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Histology and Embryology, Dalian Medical University, Dalian 116044, LiaoNing Province, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Qi
authors.affiliation: Department of Histology and Embryology, Dalian Medical University, Dalian 116044, LiaoNing Province, China.
authors.forename: Zeyu
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Otorhinolaryngology of the Second Hospital, Dalian Medical University, Dalian 116023, LiaoNing Province, China. Electronic address: konghui6905@163.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Kong
authors.affiliation: Department of Histology and Embryology, Dalian Medical University, Dalian 116044, LiaoNing Province, China. Electronic address: kongli@dlmedu.edu.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Kong
mesh_terms: D017209:Apoptosis / Q000502:physiology; D002460:Cell Line; D015536:Down-Regulation; D017127:Glycation End Products, Advanced / Q000502:physiology*; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors; D015398:Signal Transduction; D013879:Thioredoxins / Q000378:metabolism*
chemical_list: D017127:Glycation End Products, Advanced; D013879:Thioredoxins; D048670:MAP Kinase Kinase 4
keywords: Advanced glycation end products; Apoptosis; Thioredoxin