Volume 29 Issue 2
Nov.  2019
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YUAN Yan, WANG Yi, HU Fei Fei, JIANG Chen Yang, ZHANG Ya Jing, YANG Jin Long, ZHAO Shi Wen, GU Jian Hong, LIU Xue Zhong, BIAN Jian Chun, LIU Zong Ping. Cadmium Activates Reactive Oxygen Species-dependent AKT/mTOR and Mitochondrial Apoptotic Pathways in Neuronal Cells[J]. Biomedical and Environmental Sciences, 2016, 29(2): 117-126. doi: 10.3967/bes2016.013
Citation: YUAN Yan, WANG Yi, HU Fei Fei, JIANG Chen Yang, ZHANG Ya Jing, YANG Jin Long, ZHAO Shi Wen, GU Jian Hong, LIU Xue Zhong, BIAN Jian Chun, LIU Zong Ping. Cadmium Activates Reactive Oxygen Species-dependent AKT/mTOR and Mitochondrial Apoptotic Pathways in Neuronal Cells[J]. Biomedical and Environmental Sciences, 2016, 29(2): 117-126. doi: 10.3967/bes2016.013

Cadmium Activates Reactive Oxygen Species-dependent AKT/mTOR and Mitochondrial Apoptotic Pathways in Neuronal Cells

doi: 10.3967/bes2016.013
Funds:  the National Natural Science Foundation of China(31101866 and 31302058)%a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions%China Postdoctoral Science Foundation funded project(2015M581874)%Jiangsu Planned Projects for Postdoctoral Research Funds(1501072A)
  • ObjectiveTo examine the role of Cd-induced reactive oxygen species (ROS) generation in the apoptosis of neuronal cells. MethodsNeuronal cells (primary rat cerebral cortical neurons and PC12cells) 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 (mTOR) and mitochondrial apoptotic pathways were measured by western blotting or immunofluorescence assays. ResultsCd-induced activation of Akt/mTOR signaling, including Akt, mTOR,p70 S6 kinase (p70 S6K), and eukaryotic initiation factor 4E binding protein 1(4E-BP1). Rap, an mTOR inhibitor and NAC, a ROS scavenger, blocked Cd-induced activation of Akt/mTOR 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). ConclusionCd-induced ROS generation activates Akt/mTOR and mitochondrial pathways, leading to apoptosis ofneuronal cells. Our findings suggest that mTOR inhibitors or antioxidants have potential for preventing Cd-induced neurodegenerative diseases.
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通讯作者: 陈斌, bchen63@163.com
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    沈阳化工大学材料科学与工程学院 沈阳 110142

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Cadmium Activates Reactive Oxygen Species-dependent AKT/mTOR and Mitochondrial Apoptotic Pathways in Neuronal Cells

doi: 10.3967/bes2016.013
Funds:  the National Natural Science Foundation of China(31101866 and 31302058)%a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions%China Postdoctoral Science Foundation funded project(2015M581874)%Jiangsu Planned Projects for Postdoctoral Research Funds(1501072A)

Abstract: ObjectiveTo examine the role of Cd-induced reactive oxygen species (ROS) generation in the apoptosis of neuronal cells. MethodsNeuronal cells (primary rat cerebral cortical neurons and PC12cells) 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 (mTOR) and mitochondrial apoptotic pathways were measured by western blotting or immunofluorescence assays. ResultsCd-induced activation of Akt/mTOR signaling, including Akt, mTOR,p70 S6 kinase (p70 S6K), and eukaryotic initiation factor 4E binding protein 1(4E-BP1). Rap, an mTOR inhibitor and NAC, a ROS scavenger, blocked Cd-induced activation of Akt/mTOR 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). ConclusionCd-induced ROS generation activates Akt/mTOR and mitochondrial pathways, leading to apoptosis ofneuronal cells. Our findings suggest that mTOR inhibitors or antioxidants have potential for preventing Cd-induced neurodegenerative diseases.

YUAN Yan, WANG Yi, HU Fei Fei, JIANG Chen Yang, ZHANG Ya Jing, YANG Jin Long, ZHAO Shi Wen, GU Jian Hong, LIU Xue Zhong, BIAN Jian Chun, LIU Zong Ping. Cadmium Activates Reactive Oxygen Species-dependent AKT/mTOR and Mitochondrial Apoptotic Pathways in Neuronal Cells[J]. Biomedical and Environmental Sciences, 2016, 29(2): 117-126. doi: 10.3967/bes2016.013
Citation: YUAN Yan, WANG Yi, HU Fei Fei, JIANG Chen Yang, ZHANG Ya Jing, YANG Jin Long, ZHAO Shi Wen, GU Jian Hong, LIU Xue Zhong, BIAN Jian Chun, LIU Zong Ping. Cadmium Activates Reactive Oxygen Species-dependent AKT/mTOR and Mitochondrial Apoptotic Pathways in Neuronal Cells[J]. Biomedical and Environmental Sciences, 2016, 29(2): 117-126. doi: 10.3967/bes2016.013

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