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Cadmium Activates Reactive Oxygen Species-dependent AKT/mT OR and Mitochondrial Apoptotic Pathways in Neuronal Cells 被引量:8

Cadmium Activates Reactive Oxygen Species-dependent AKT/mT OR and Mitochondrial Apoptotic Pathways in Neuronal Cells
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摘要 Objective To examine the role of Cd-induced reactive oxygen species(ROS) generation in the apoptosis of neuronal cells. Methods Neuronal cells(primary rat cerebral cortical neurons and PC12 cells) were incubated with or without Cd post-pretreatment with rapamycin(Rap) or N-acetyl-L-cysteine(NAC). Cell viability was determined by MTT assay, apoptosis was examined using flow cytometry and fluorescence microscopy, and the activation of phosphoinositide 3’-kinase/protein kinase B(Akt)/mammalian target of rapamycin(m TOR) and mitochondrial apoptotic pathways were measured by western blotting or immunofluorescence assays. Results Cd-induced activation of Akt/m TOR signaling, including Akt, m TOR, p70 S6 kinase(p70 S6K), and eukaryotic initiation factor 4E binding protein 1(4E-BP1). Rap, an m TOR inhibitor and NAC, a ROS scavenger, blocked Cd-induced activation of Akt/m TOR signaling and apoptosis of neuronal cells. Furthermore, NAC blocked the decrease of B-cell lymphoma 2/Bcl-2 associated X protein(Bcl-2/Bax) ratio, release of cytochrome c, cleavage of caspase-3 and poly(ADP-ribose) polymerase(PARP), and nuclear translocation of apoptosis-inducing factor(AIF) and endonuclease G(Endo G). Conclusion Cd-induced ROS generation activates Akt/m TOR and mitochondrial pathways, leading to apoptosis of neuronal cells. Our findings suggest that m TOR inhibitors or antioxidants have potential for preventing Cd-induced neurodegenerative diseases. Objective To examine the role of Cd-induced reactive oxygen species(ROS) generation in the apoptosis of neuronal cells. Methods Neuronal cells(primary rat cerebral cortical neurons and PC12 cells) were incubated with or without Cd post-pretreatment with rapamycin(Rap) or N-acetyl-L-cysteine(NAC). Cell viability was determined by MTT assay, apoptosis was examined using flow cytometry and fluorescence microscopy, and the activation of phosphoinositide 3’-kinase/protein kinase B(Akt)/mammalian target of rapamycin(m TOR) and mitochondrial apoptotic pathways were measured by western blotting or immunofluorescence assays. Results Cd-induced activation of Akt/m TOR signaling, including Akt, m TOR, p70 S6 kinase(p70 S6K), and eukaryotic initiation factor 4E binding protein 1(4E-BP1). Rap, an m TOR inhibitor and NAC, a ROS scavenger, blocked Cd-induced activation of Akt/m TOR signaling and apoptosis of neuronal cells. Furthermore, NAC blocked the decrease of B-cell lymphoma 2/Bcl-2 associated X protein(Bcl-2/Bax) ratio, release of cytochrome c, cleavage of caspase-3 and poly(ADP-ribose) polymerase(PARP), and nuclear translocation of apoptosis-inducing factor(AIF) and endonuclease G(Endo G). Conclusion Cd-induced ROS generation activates Akt/m TOR and mitochondrial pathways, leading to apoptosis of neuronal cells. Our findings suggest that m TOR inhibitors or antioxidants have potential for preventing Cd-induced neurodegenerative diseases.
出处 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2016年第2期117-126,共10页 生物医学与环境科学(英文版)
基金 supported by the National Natural Science Foundation of China(No.31101866 and 31302058) a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD),China Postdoctoral Science Foundation funded project(2015M581874) Jiangsu Planned Projects for Postdoctoral Research Funds(1501072A)
关键词 CADMIUM Apoptosis AKT/m TOR pathway Mitochondrial apoptotic pathway Primary rat cerebral cortical neurons PC12 cells Cadmium Apoptosis AKT/m TOR pathway Mitochondrial apoptotic pathway Primary rat cerebral cortical neurons PC12 cells
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