PMID- 31622878
OWN - NLM
STAT- MEDLINE
DCOM- 20200117
LR  - 20200117
IS  - 1090-2414 (Electronic)
IS  - 0147-6513 (Linking)
VI  - 186
DP  - 2019 Dec 30
TI  - Blockage of ROS-ERK-DLP1 signaling and mitochondrial fission alleviates 
      Cr(VI)-induced mitochondrial dysfunction in L02 hepatocytes.
PG  - 109749
LID - S0147-6513(19)31080-2 [pii]
LID - 10.1016/j.ecoenv.2019.109749 [doi]
AB  - Hexavalent chromium [Cr(VI)] is a common heavy metal pollutant widely used in 
      various industrial fields. It is well known that mitochondria are the most 
      vulnerable targets of heavy metals, but the key molecule/event that directly 
      mediated mitochondrial dysfunction after Cr(VI) exposure is still unclear. The 
      present study was aimed to explore whether Cr(VI) exposure could affect the 
      mitochondrial fission/fusion process, and whether the related abnormal 
      mitochondrial dynamics have been implicated in Cr(VI)-induced mitochondrial 
      dysfunction. We found that the mitochondrial dysfunction caused by Cr(VI) 
      exposure was characterized by decreased mitochondrial respiratory chain complex 
      (MRCC) I/II activities and levels, collapsed mitochondrial membrane potential 
      (MMP), depleted ATP, and increased reactive oxygen species (ROS) level. Cr(VI) 
      induced abnormal mitochondrial fission/fusion events, the antioxidant 
      Nacetyl-L-cysteine (NAC) restored the abnormal mitochondrial function as well as 
      the fission/fusion dynamics. ROS was the up-stream regulator of extracellular 
      regulated protein kinases (ERK) signaling, and the application of a specific 
      ERK1/2 inhibitor PD98059 confirmed that activation of ERK1/2 signaling was 
      associated with the abnormal mitochondrial fission/fusion and mitochondrial 
      dysfunction. We also demonstrated that treatment with dynamic-like protein 1 
      (DLP1)-siRNA rescued mitochondrial dysfunction in Cr(VI)-exposed L02 hepatocytes. 
      We reached the conclusion that blockage of ROS-ERK-DLP1 signaling and 
      mitochondrial fission alleviates Cr(VI)-induced mitochondrial dysfunction in L02 
      hepatocytes, which may provide the new avenue for developing effective strategies 
      to protect against Cr(VI)-induced hepatotoxicity.
CI  - Copyright (c) 2019 Elsevier Inc. All rights reserved.
FAU - Zhang, Yujing
AU  - Zhang Y
AD  - Department of Health Toxicology, Xiangya School of Public Health, Central South 
      University, Changsha, 410078, PR China.
FAU - Ma, Yu
AU  - Ma Y
AD  - Department of Health Toxicology, Xiangya School of Public Health, Central South 
      University, Changsha, 410078, PR China.
FAU - Liang, Ningjuan
AU  - Liang N
AD  - Department of Health Toxicology, Xiangya School of Public Health, Central South 
      University, Changsha, 410078, PR China.
FAU - Liang, Yuehui
AU  - Liang Y
AD  - Department of Health Toxicology, Xiangya School of Public Health, Central South 
      University, Changsha, 410078, PR China.
FAU - Lu, Chan
AU  - Lu C
AD  - Department of Health Toxicology, Xiangya School of Public Health, Central South 
      University, Changsha, 410078, PR China.
FAU - Xiao, Fang
AU  - Xiao F
AD  - Department of Health Toxicology, Xiangya School of Public Health, Central South 
      University, Changsha, 410078, PR China. Electronic address: fangxiao@csu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20191014
PL  - Netherlands
TA  - Ecotoxicol Environ Saf
JT  - Ecotoxicology and environmental safety
JID - 7805381
RN  - 0 (Antioxidants)
RN  - 0 (Carcinogens, Environmental)
RN  - 0 (Flavonoids)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Reactive Oxygen Species)
RN  - 0R0008Q3JB (Chromium)
RN  - 18540-29-9 (chromium hexavalent ion)
RN  - EC 2.7.11.24 (MAPK1 protein, human)
RN  - EC 2.7.11.24 (MAPK3 protein, human)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 3.6.5.5 (DNM1L protein, human)
RN  - EC 3.6.5.5 (Dynamins)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/pharmacology
MH  - Antioxidants/*pharmacology
MH  - Carcinogens, Environmental
MH  - Chromium/*toxicity
MH  - Dynamins/metabolism/*pharmacology
MH  - Flavonoids/pharmacology
MH  - Hepatocytes/drug effects/physiology
MH  - Humans
MH  - Liver/cytology/*drug effects/metabolism/physiopathology
MH  - MAP Kinase Signaling System/*drug effects
MH  - Membrane Potential, Mitochondrial/drug effects
MH  - Mitochondria/*drug effects/physiology
MH  - Mitochondrial Dynamics/drug effects
MH  - Mitogen-Activated Protein Kinase 1/metabolism
MH  - Mitogen-Activated Protein Kinase 3/metabolism
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Reactive Oxygen Species/*metabolism
MH  - Signal Transduction
OTO - NOTNLM
OT  - Dynamic-like protein 1 (DLP1)
OT  - Extracellular regulated protein kinases (ERK)
OT  - Hexavalent chromium [Cr(VI)]
OT  - Mitochondrial dysfunction
OT  - Reactive oxygen species (ROS)
EDAT- 2019/10/18 06:00
MHDA- 2020/01/18 06:00
CRDT- 2019/10/18 06:00
PHST- 2019/07/05 00:00 [received]
PHST- 2019/09/23 00:00 [revised]
PHST- 2019/10/01 00:00 [accepted]
PHST- 2019/10/18 06:00 [pubmed]
PHST- 2020/01/18 06:00 [medline]
PHST- 2019/10/18 06:00 [entrez]
AID - S0147-6513(19)31080-2 [pii]
AID - 10.1016/j.ecoenv.2019.109749 [doi]
PST - ppublish
SO  - Ecotoxicol Environ Saf. 2019 Dec 30;186:109749. doi: 
      10.1016/j.ecoenv.2019.109749. Epub 2019 Oct 14.