PMID- 27173049
OWN - NLM
STAT- MEDLINE
DCOM- 20170323
LR  - 20211203
IS  - 1618-0631 (Electronic)
IS  - 0344-0338 (Linking)
VI  - 212
IP  - 6
DP  - 2016 Jun
TI  - ER stress contributes to alpha-naphthyl isothiocyanate-induced liver injury with 
      cholestasis in mice.
PG  - 560-7
LID - S0344-0338(16)30081-4 [pii]
LID - 10.1016/j.prp.2016.05.001 [doi]
AB  - Endoplasmic reticulum (ER) stress is involved in the development of several liver 
      diseases and tumors. This study investigated the underlying mechanisms of 
      alpha-naphthyl isothiocyanate (ANIT)-induced liver injury with cholestasis in mice 
      and found ER stress contributes to the injury. All animals were randomly divided 
      into three groups. In the ANIT-intoxicated group, mice were intragastrically 
      given 100mg/kg ANIT (dissolved in corn oil), while the other groups received an 
      equal volume of vehicle as control. After 24 and 48h of ANIT administration, 
      blood samples and liver tissues of all animals were collected for serum 
      biochemistry and hepatic histopathological examinations to evaluate liver 
      injuries with cholestasis. Hepatocellular apoptosis was assessed by the terminal 
      deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. The expression 
      of hepatic ER stress-related markers was determined by real-time PCR, 
      immunohistochemical assay and Western blot. ANIT was found to significantly 
      induce liver injury with cholestasis compared with control mice as evidenced by 
      the increase of serum transaminases and total bilirubin (TBil), and 
      histopathological changes in mice. ANIT remarkably induced hepatocellular 
      apoptosis, upregulated the expression of caspase-9 and cytochrome c, and 
      inhibited the gene and protein expression of proliferating cell nuclear antigen 
      (PCNA). The gene expression of ER stress-related markers, including 
      glucose-regulated protein 78 (GRP78), protein kinase R-like ER kinase (PERK), 
      eukaryotic initiation factor 2alpha (eIF2alpha), inositol requiring enzyme-1alpha (IRE-1alpha) 
      and activating transcription factor 6 (ATF6) was upregulated by ANIT in mice. 
      ANIT also upregulated the protein expression of GRP78 and activated the 
      phosphorylation of IRE1. These results suggested that ANIT induced liver injury 
      with cholestasis partly due to its ability to activate the ER stress pathway.
CI  - Copyright (c) 2016 Elsevier GmbH. All rights reserved.
FAU - Yao, Xiaomin
AU  - Yao X
AD  - Faculty of Pharmacy, Zhejiang Pharmaceutical College, Ningbo, 315100, China. 
      Electronic address: 630088408@qq.com.
FAU - Li, Yue
AU  - Li Y
AD  - Beijing Centre For Physical & Chemical Analysis, Beijing, 100050, China.
FAU - Cheng, Xiaoyan
AU  - Cheng X
AD  - Beijing Centre For Physical & Chemical Analysis, Beijing, 100050, China.
FAU - Li, Hongwei
AU  - Li H
AD  - Faculty of Pharmacy, Zhejiang Pharmaceutical College, Ningbo, 315100, China.
LA  - eng
PT  - Journal Article
DEP - 20160503
PL  - Germany
TA  - Pathol Res Pract
JT  - Pathology, research and practice
JID - 7806109
RN  - 0 (Endoplasmic Reticulum Chaperone BiP)
RN  - 0 (Hspa5 protein, mouse)
RN  - 0 (Isocyanates)
RN  - 0 (Naphthalenes)
RN  - 5LH2P0691E (alpha-naphthyl isocyanate)
RN  - 9007-43-6 (Cytochromes c)
RN  - EC 3.4.22.- (Caspase 9)
SB  - IM
MH  - Animals
MH  - Apoptosis/physiology
MH  - Caspase 9/metabolism
MH  - Chemical and Drug Induced Liver Injury/complications/*metabolism/pathology
MH  - Cholestasis/chemically induced/complications/*metabolism/pathology
MH  - Cytochromes c/metabolism
MH  - Endoplasmic Reticulum Chaperone BiP
MH  - Endoplasmic Reticulum Stress/*physiology
MH  - Isocyanates
MH  - Liver/*metabolism/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Naphthalenes
OTO - NOTNLM
OT  - Alpha-naphthyl isothiocyanate
OT  - Apoptosis
OT  - Cholestasis
OT  - ER stress
OT  - Liver injury
EDAT- 2016/05/14 06:00
MHDA- 2017/03/24 06:00
CRDT- 2016/05/14 06:00
PHST- 2016/02/18 00:00 [received]
PHST- 2016/04/28 00:00 [revised]
PHST- 2016/05/02 00:00 [accepted]
PHST- 2016/05/14 06:00 [entrez]
PHST- 2016/05/14 06:00 [pubmed]
PHST- 2017/03/24 06:00 [medline]
AID - S0344-0338(16)30081-4 [pii]
AID - 10.1016/j.prp.2016.05.001 [doi]
PST - ppublish
SO  - Pathol Res Pract. 2016 Jun;212(6):560-7. doi: 10.1016/j.prp.2016.05.001. Epub 
      2016 May 3.