PMID- 31976833
OWN - NLM
STAT- MEDLINE
DCOM- 20211122
LR  - 20211204
IS  - 1875-5666 (Electronic)
IS  - 1566-5240 (Linking)
VI  - 20
IP  - 7
DP  - 2020
TI  - Endoplasmic Reticulum Stress Increases Multidrug-resistance Protein 2 Expression 
      and Mitigates Acute Liver Injury.
PG  - 548-557
LID - 10.2174/1566524020666200124102411 [doi]
AB  - BACKGROUND: Multidrug-resistance protein (MRP) 2 is a key membrane transporter 
      that is expressed on hepatocytes and regulated by nuclear factor kappa B (NF-kappaB). 
      Interestingly, endoplasmic reticulum (ER) stress is closely associated with liver 
      injury and the activation of NF-kappaB signaling. OBJECTIVE: Here, we investigated 
      the impact of ER stress on MRP2 expression and the functional involvement of MRP2 
      in acute liver injury. METHODS: ER stress, MRP2 expression, and hepatocyte injury 
      were analyzed in a carbon tetrachloride (CCl4)-induced mouse model of acute liver 
      injury and in a thapsigargin (TG)-induced model of ER stress. RESULTS: CCl4 and 
      TG induced significant ER stress, MRP2 protein expression and NF- kappaB activation 
      in mice and LO2 cells (P < 0.05). Pretreatment with ER stress inhibitor 4- phenyl 
      butyric acid (PBA) significantly mitigated CCl4 and TG-induced ER stress and MRP2 
      protein expression (P < 0.05). Moreover, pretreatment with pyrrolidine 
      dithiocarbamic acid (PDTC; NF-kappaB inhibitor) significantly inhibited CCl4-induced 
      NF-kappaB activation and reduced MRP2 protein expression (1+/-0.097 vs. 0.623+/-0.054; P 
      < 0.05). Furthermore, hepatic downregulation of MRP2 expression significantly 
      increased CCl4- induced ER stress, apoptosis, and liver injury. CONCLUSION: ER 
      stress enhances intrahepatic MRP2 protein expression by activating NF-kappaB. This 
      increase in MRP2 expression mitigates ER stress and acute liver injury.
CI  - Copyright(c) Bentham Science Publishers; For any queries, please email at 
      epub@benthamscience.net.
FAU - Huang, Wen-Ge
AU  - Huang WG
AD  - Department of Infectious Diseases, the Affiliated Hospital of Zunyi Medical 
      University, Zunyi, 563003, Guizhou, China.
FAU - Wang, Jun
AU  - Wang J
AD  - Department of Infectious Diseases, the Affiliated Hospital of Zunyi Medical 
      University, Zunyi, 563003, Guizhou, China.
FAU - Liu, Yu-Juan
AU  - Liu YJ
AD  - Department of Infectious Diseases, the Affiliated Hospital of Zunyi Medical 
      University, Zunyi, 563003, Guizhou, China.
FAU - Wang, Hong-Xia
AU  - Wang HX
AD  - Department of Infectious Diseases, the Affiliated Hospital of Zunyi Medical 
      University, Zunyi, 563003, Guizhou, China.
FAU - Zhou, Si-Zhen
AU  - Zhou SZ
AD  - Department of Infectious Diseases, the Affiliated Hospital of Zunyi Medical 
      University, Zunyi, 563003, Guizhou, China.
FAU - Chen, Huan
AU  - Chen H
AD  - Department of Infectious Diseases, the Affiliated Hospital of Zunyi Medical 
      University, Zunyi, 563003, Guizhou, China.
FAU - Yang, Fang-Wan
AU  - Yang FW
AD  - Department of Infectious Diseases, the Affiliated Hospital of Zunyi Medical 
      University, Zunyi, 563003, Guizhou, China.
FAU - Li, Ying
AU  - Li Y
AD  - Department of Infectious Diseases, the Affiliated Hospital of Zunyi Medical 
      University, Zunyi, 563003, Guizhou, China.
FAU - Yi, Yu
AU  - Yi Y
AD  - Department of Infectious Diseases, the Affiliated Hospital of Zunyi Medical 
      University, Zunyi, 563003, Guizhou, China.
FAU - He, Yi-Huai
AU  - He YH
AD  - Department of Infectious Diseases, the Affiliated Hospital of Zunyi Medical 
      University, Zunyi, 563003, Guizhou, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Curr Mol Med
JT  - Current molecular medicine
JID - 101093076
RN  - 0 (Multidrug Resistance-Associated Protein 2)
RN  - 0 (Multidrug Resistance-Associated Proteins)
RN  - 0 (NF-kappa B)
RN  - CL2T97X0V0 (Carbon Tetrachloride)
SB  - IM
MH  - Animals
MH  - *Apoptosis
MH  - Carbon Tetrachloride/toxicity
MH  - Chemical and Drug Induced Liver Injury/etiology/metabolism/pathology/*prevention 
      & control
MH  - *Endoplasmic Reticulum Stress
MH  - Hepatocytes/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Multidrug Resistance-Associated Protein 2
MH  - Multidrug Resistance-Associated Proteins/genetics/*metabolism
MH  - NF-kappa B/genetics/metabolism
MH  - Phosphorylation
MH  - Signal Transduction
OTO - NOTNLM
OT  - Multidrug-resistance protein 2
OT  - acute liver injury
OT  - apoptosis
OT  - endoplasmic reticulum stress
OT  - necroptosis
OT  - nuclear factor kappa B
EDAT- 2020/01/25 06:00
MHDA- 2021/11/23 06:00
CRDT- 2020/01/25 06:00
PHST- 2019/10/26 00:00 [received]
PHST- 2019/12/30 00:00 [revised]
PHST- 2020/01/12 00:00 [accepted]
PHST- 2020/01/25 06:00 [pubmed]
PHST- 2021/11/23 06:00 [medline]
PHST- 2020/01/25 06:00 [entrez]
AID - CMM-EPUB-103889 [pii]
AID - 10.2174/1566524020666200124102411 [doi]
PST - ppublish
SO  - Curr Mol Med. 2020;20(7):548-557. doi: 10.2174/1566524020666200124102411.