PMID- 25224493
OWN - NLM
STAT- MEDLINE
DCOM- 20150720
LR  - 20220410
IS  - 1873-6823 (Electronic)
IS  - 0741-8329 (Linking)
VI  - 48
IP  - 7
DP  - 2014 Nov
TI  - Impairment of autophagosome-lysosome fusion contributes to chronic 
      ethanol-induced liver injury.
PG  - 717-25
LID - S0741-8329(14)00136-0 [pii]
LID - 10.1016/j.alcohol.2014.08.006 [doi]
AB  - The pathogenic mechanism underlying alcoholic fatty liver (AFL) is not clear. 
      Autophagy is a self-digestion process that is critical for the maintenance of 
      cellular homeostasis and regulation of lipid metabolism. We investigated the role 
      of autophagy and autophagic flux in hepatic injury induced by chronic ethanol 
      feeding in mice. C57BL/6 mice were fed a Lieber-DeCarli ethanol diet (ED) to 
      induce AFL or an isocaloric control diet for 6 weeks. Chloroquine (CQ, 10 mg/kg, 
      intra-peritoneally [i.p.]) or rapamycin (Rapa, 5 mg/kg, i.p.) were administered 
      during the last 2 weeks of the experimental period. Chronic ethanol feeding 
      induced AFL with focal necrosis associated with increased levels of hepatic 
      triglyceride. This phenomenon was aggravated by CQ, an inhibitor of autophagy, 
      and attenuated by Rapa, an inducer of autophagy. Expression of 
      microtubule-associated protein 1 light chain 3 (LC3)-II and sequestosome1/p62 
      significantly increased in the ED group. Moreover, accumulation of autophagosomes 
      was observed by transmission electron microscopy in chronic ethanol-treated mice. 
      Chronic ethanol consumption decreased protein expression of LC3 
      lipidation-related proteins Atg3 and Atg7, and the lysosomal proteins 
      lysosome-associated membrane protein-2 and Rab7, and increased the protein 
      expression of calpain 1 and phosphorylated mammalian target of rapamycin. Taken 
      together, these findings suggest that chronic ethanol consumption leads to 
      impairment of autophagic flux, which contributes to ethanol-induced liver injury.
CI  - Copyright (c) 2014 Elsevier Inc. All rights reserved.
FAU - Cho, Hong-Ik
AU  - Cho HI
AD  - School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
FAU - Choi, Joo-Wan
AU  - Choi JW
AD  - School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
FAU - Lee, Sun-Mee
AU  - Lee SM
AD  - School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea. 
      Electronic address: sunmee@skku.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140821
PL  - United States
TA  - Alcohol
JT  - Alcohol (Fayetteville, N.Y.)
JID - 8502311
RN  - 0 (Anti-Bacterial Agents)
RN  - 3K9958V90M (Ethanol)
RN  - 886U3H6UFF (Chloroquine)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Anti-Bacterial Agents/pharmacology
MH  - Autophagy/*drug effects/physiology
MH  - Chloroquine/pharmacology
MH  - Ethanol/adverse effects
MH  - Liver/drug effects/ultrastructure
MH  - Liver Diseases, Alcoholic/*etiology
MH  - Lysosomes/*drug effects/physiology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Microscopy, Electron, Transmission
MH  - Sirolimus/pharmacology
OTO - NOTNLM
OT  - Alcoholic fatty liver
OT  - Autolysosome
OT  - Autophagic flux
OT  - Autophagosome
OT  - Chronic ethanol consumption
OT  - LC3 lipidation
EDAT- 2014/09/17 06:00
MHDA- 2015/07/21 06:00
CRDT- 2014/09/17 06:00
PHST- 2014/09/17 06:00 [entrez]
PHST- 2014/09/17 06:00 [pubmed]
PHST- 2015/07/21 06:00 [medline]
AID - S0741-8329(14)00136-0 [pii]
AID - 10.1016/j.alcohol.2014.08.006 [doi]
PST - ppublish
SO  - Alcohol. 2014 Nov;48(7):717-25. doi: 10.1016/j.alcohol.2014.08.006. Epub 2014 Aug 
      21.