Cadmium Activates Reactive Oxygen Species-dependent AKT/mTOR and Mitochondrial Apoptotic Pathways in Neuronal Cells.
- Author:
Yan YUAN
1
,
2
;
Yi WANG
1
;
Fei Fei HU
1
;
Chen Yang JIANG
1
;
Ya Jing ZHANG
1
;
Jin Long YANG
1
;
Shi Wen ZHAO
1
;
Jian Hong GU
1
;
Xue Zhong LIU
1
;
Jian Chun BIAN
1
;
Zong Ping LIU
1
;
Author Information
- Publication Type:Journal Article
- Keywords: AKT/mTOR pathway; Apoptosis; Cadmium; Mitochondrial apoptotic pathway; PC12 cells; Primary rat cerebral cortical neurons
- MeSH: Animals; Apoptosis; drug effects; Cadmium; toxicity; Caspases; metabolism; Mitochondria; drug effects; Neurons; drug effects; PC12 Cells; Proto-Oncogene Proteins c-akt; metabolism; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; metabolism; Signal Transduction; drug effects; TOR Serine-Threonine Kinases; metabolism
- From: Biomedical and Environmental Sciences 2016;29(2):117-126
- CountryChina
- Language:English
-
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 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.
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 of neuronal cells. Our findings suggest that mTOR inhibitors or antioxidants have potential for preventing Cd-induced neurodegenerative diseases.