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

Content Provider	Semantic Scholar
Author	Yuan, Yan Ni Wang, Yi Hu, Fei Fei Jiang, Chen Zhang, Ya Jing Yang, Jin Long Zhao, Shi Wen Gu, Jian Hong Liu, Xue Zhong Bian, Jianchun Liu, Zong Ping
Copyright Year	2016
Abstract	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 (mTOR) and mitochondrial apoptotic pathways were measured by western blotting or immunofluorescence assays. RESULTS Cd-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). CONCLUSION Cd-induced ROS generation activates Akt/mTOR and mitochondrial pathways, leading to apoptosis of neuronal cells. Our findings suggest that mTOR inhibitors or antioxidants have potential for preventing Cd-induced neurodegenerative diseases.
Starting Page	7
Ending Page	7
Page Count	1
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://www.besjournal.com/Articles/Archive/2016/No2/201603/P020160309506616752340.pdf
PubMed reference number	27003169v1
Alternate Webpage(s)	https://doi.org/10.3967/bes2016.013
DOI	10.3967/bes2016.013
Journal	Biomedical and environmental sciences : BES
Volume Number	29
Issue Number	2
Language	English
Access Restriction	Open
Subject Keyword	Acetylcysteine Antioxidants Apoptosis Cadmium FRAP1 protein, human Flow Cytometry Fluorescence Gas Scavengers Immunofluorescence assay Leukemia, B-Cell Mitochondrial Inheritance Neurodegenerative Disorders Nuclear Translocation PC12 Cells Peptide Initiation Factors Phosphatidylinositols Poly(ADP-ribose) Polymerases Protein Kinases Proto-Oncogene Proteins c-akt Reactive Oxygen Species Ribose Sirolimus Transcription Initiation Western Blotting caspase-3 endonuclease incubated mTOR Inhibitor monooxyethylene trimethylolpropane tristearate ribosomal protein S6 kinase, 70kD, polypeptide 2
Content Type	Text
Resource Type	Article