PMID- 30504711
OWN - NLM
STAT- MEDLINE
DCOM- 20190121
LR  - 20211204
IS  - 1421-9778 (Electronic)
IS  - 1015-8987 (Linking)
VI  - 51
IP  - 4
DP  - 2018
TI  - Cr(VI)-Induced Autophagy Protects L-02 Hepatocytes from Apoptosis Through the 
      ROS-AKT-mTOR Pathway.
PG  - 1863-1878
LID - 10.1159/000495713 [doi]
AB  - BACKGROUND/AIMS: Hexavalent chromium [Cr(VI)] pollution has become a global 
      concern for both ecosystems and human health. Our previous study revealed Cr(VI) 
      could induce both apoptosis and autophagy in L-02 hepatocytes. Here, we sought to 
      explore the underlying mechanism of Cr(VI)-induced autophagy and its exact role 
      in cell death. METHODS: Autophagy ultrastructure was observed under transmission 
      electron microscope (TEM), autophagy flux was measured with double-tagged 
      mCherry-green fluorescent protein (GFP)-microtubule-associated protein 1 light 
      chain 3 (LC3) assay, long-lived protein degradation assay, and LC3II expression 
      assay in the presence of lysosomal inhibitor, bafilomycin A1 (BafA1). Reactive 
      oxygen species (ROS) level was determined using fluorescent probe 
      dichloro-dihydrofluorescein diacetate (DCFH-DA). The expression levels of 
      Beclin-1, LC3, p62/ SQSTM1, and AKT-mammalian target of rapamycin (mTOR) 
      pathway-related molecules including phosphorylation (p)-AKT, AKT, p-mTOR, and 
      mTOR were examined using real-time polymerase chain reaction (RT-PCR) and western 
      blotting. Apoptosis was determined using Annexin V- fluorescein isothiocyanate 
      (FITC)/propidium iodide (PI) staining. RESULTS: Our results demonstrated Cr(VI) 
      exposure activated autophagy in L-02 hepatocytes, as evidenced by the 
      accumulation of autophagosomes, the increase of LC3-II and degradation of p62/ 
      SQSTM1, and the enhanced overall degradation of proteins. We also confirmed 
      Cr(VI)-induced LC3-II elevation mainly came from autophagy induction rather than 
      lysosomal degradation impairment. ROS-AKT-mTOR pathway was associated with 
      Cr(VI)-induced autophagy, and ROS scavenger N-acetylcysteine (NAC) pretreatment 
      inhibited Cr(VI)-induced autophagy by alleviating the inhibition of the AKT-mTOR 
      pathway. Autophagy inhibitors 3-methyladenine (3-MA) and chloroquine diphosphate 
      (CDP) promoted Cr(VI)-induced apoptotic death. CONCLUSION: These findings 
      indicated Cr(VI)-induced autophagy protected L-02 hepatocytes from apoptosis 
      through the ROS-AKT-mTOR pathway.
CI  - (c) 2018 The Author(s). Published by S. Karger AG, Basel.
FAU - Liang, Qi
AU  - Liang Q
AD  - Department of Radiology, The Third Xiangya Hospital, Central South University, 
      Changsha, China.
FAU - Xiao, Yuanyuan
AU  - Xiao Y
AD  - Department of Health Toxicology, Xiangya School of Public Health, Central South 
      University, Changsha, China.
FAU - Liu, Kaihua
AU  - Liu K
AD  - Department of Health Toxicology, Xiangya School of Public Health, Central South 
      University, Changsha, China.
FAU - Zhong, Caigao
AU  - Zhong C
AD  - Department of Health Toxicology, Xiangya School of Public Health, Central South 
      University, Changsha, China.
FAU - Zeng, Ming
AU  - Zeng M
AD  - Department of Health Toxicology, Xiangya School of Public Health, Central South 
      University, Changsha, China.
FAU - Xiao, Fang
AU  - Xiao F
AD  - Department of Health Toxicology, Xiangya School of Public Health, Central South 
      University, Changsha, Chinafangxiao@csu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20181130
PL  - Germany
TA  - Cell Physiol Biochem
JT  - Cellular physiology and biochemistry : international journal of experimental 
      cellular physiology, biochemistry, and pharmacology
JID - 9113221
RN  - 0 (Free Radical Scavengers)
RN  - 0 (Reactive Oxygen Species)
RN  - 0R0008Q3JB (Chromium)
RN  - 18540-29-9 (chromium hexavalent ion)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/pharmacology
MH  - Apoptosis/*drug effects
MH  - Autophagy/*drug effects
MH  - Cell Line
MH  - Chromium/*adverse effects
MH  - Cytoprotection/drug effects
MH  - Free Radical Scavengers/pharmacology
MH  - Hepatocytes/cytology/*drug effects/metabolism
MH  - Humans
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction/*drug effects
MH  - TOR Serine-Threonine Kinases/metabolism
OTO - NOTNLM
OT  - AKT-mTOR
OT  - Apoptosis
OT  - Autophagy
OT  - Cr(VI)
OT  - L-02 hepatocytes
OT  - ROS
EDAT- 2018/12/07 06:00
MHDA- 2019/01/22 06:00
CRDT- 2018/12/04 06:00
PHST- 2017/09/19 00:00 [received]
PHST- 2018/11/23 00:00 [accepted]
PHST- 2018/12/07 06:00 [pubmed]
PHST- 2019/01/22 06:00 [medline]
PHST- 2018/12/04 06:00 [entrez]
AID - 000495713 [pii]
AID - 10.1159/000495713 [doi]
PST - ppublish
SO  - Cell Physiol Biochem. 2018;51(4):1863-1878. doi: 10.1159/000495713. Epub 2018 Nov 
      30.