title: ZnT7 can protect MC3T3-E1 cells from oxidative stress-induced apoptosis via PI3K/Akt and MAPK/ERK signaling pathways.
abstract: The osteoblasts could be lead to the occurrence of apoptosis by oxidative stress. The zinc transporter family SLC30A (ZnTs) plays an important role in the regulation of zinc homeostasis, however, its function in apoptosis of MC3T3-E1 cells remains unknown. This study was aimed to investigate the role of zinc transporters in cell survival, particularly in MC3T3-E1 cells, during oxidative stress, and the molecular mechanism involved. Our study found that hydrogen peroxide can induce zinc-overloaded in the cells. While high concentration of zinc plays an important role in inducing apoptosis of the MC3T3-E1 cells, we demonstrated that ZnT7 can protect MC3T3-E1 cells and reduce the aggregation of intracellular free zinc ions as well as inhibit apoptosis induced by H2O2. Moreover, ZnT7 overexpression enhanced the anti-apoptotic effects. Interestingly, suppression of ZnT7 by siRNA could significantly exacerbate apoptosis in MC3T3-E1 cells. We also found that ZnT7 promotes cell survival via two distinct signaling pathways involving activation of the PI3K/Akt-mediated survival pathway and activation of MAPK/ERK pathway. Collectively, these results suggest that ZnT7 overexpression significantly protects osteoblasts cells from apoptosis induced by H2O2. This effect is mediated, at least in part, through activation of PI3K/Akt and MAPK/ERK pathways.
authors: Troops of 95935 Unit Haerbin, PR China.
authors: Dan
authors: D
authors: Liang
authors: Liangbi
authors: L
authors: Xiang
authors: Maowei
authors: M
authors: Yang
authors: Xiuli
authors: X
authors: Zhang
authors: Baolei
authors: B
authors: Guo
authors: Yu
authors: Y
authors: Chen
authors: Lei
authors: L
authors: Yang
authors: Junjun
authors: J
authors: Cao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D027682:Cation Transport Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000633:toxicity; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D018384:Oxidative Stress; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D027682:Cation Transport Proteins; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; C472293:ZnT7 protein, mouse; D006861:Hydrogen Peroxide; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D020929:Mitogen-Activated Protein Kinase Kinases