PMID- 15041894
OWN - NLM
STAT- MEDLINE
DCOM- 20040419
LR  - 20190919
IS  - 1665-2681 (Print)
IS  - 1665-2681 (Linking)
VI  - 2
IP  - 2
DP  - 2003 Apr-Jun
TI  - Alcohol-induced liver disease: when fat and oxidative stress meet.
PG  - 69-75
AB  - Reactive oxygen species (ROS) act as signaling intermediates regulating multiple 
      cellular processes. The fate and disposal of the signaling species are determined 
      by the actions of antioxidants, particularly glutathione (GSH). The mitochondrial 
      pool of GSH (mGSH) arises from the transport of cytosol GSH by a specific 
      mitochondrial carrier and is responsible for the maintenance of a healthy 
      competent organelle. The depletion of mGSH upon impairment of the mitochondrial 
      transport activity leaves mitochondria unprotected from damaging effects of ROS 
      overgeneration within the mitochondrial electron transport chain. Tumor necrosis 
      factor-alpha (TNF-alpha) has emerged as a key player in the progression of the 
      alcohol-induced liver disease (ALD), and is known to target mitochondria. Key 
      components of TNF signaling include sphingolipids, particularly ceramide 
      generated from acidic sphingomyelinase activation serving as a source for 
      gangliosides. In experimental models alcohol consumption enhances cholesterol 
      levels and subsequent deposition into mitochondria resulting in selective 
      decrease in the mGSH stores which is sufficient by itself to sensitize 
      hepatocytes to TNF-alpha-mediated cell death. Thus, the combination of TNF-alpha 
      overproduction, enhanced glycosphingolipid generation and selective mGSH 
      depletion by alcohol intake cooperate making the liver sensitive to alcohol.
FAU - Fernandez-Checa, Jose C
AU  - Fernandez-Checa JC
AD  - Liver Unit, Instituto Malalties Digestives, Hospital Clinic i Provincial, 
      Instituto Investigaciones Biomedicas August Pi i Sunyer, and Department of 
      Experimental Pathology, Instituto Investigaciones Biomedicas Barcelona, Spain. 
      checa229@yahoo.com
LA  - eng
GR  - 1R21 AA014135-01/AA/NIAAA NIH HHS/United States
GR  - P50 AA11999/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - Mexico
TA  - Ann Hepatol
JT  - Annals of hepatology
JID - 101155885
RN  - 0 (Fats)
SB  - IM
MH  - Fats/*metabolism
MH  - Humans
MH  - Liver Diseases, Alcoholic/*metabolism
MH  - *Oxidative Stress
RF  - 61
EDAT- 2004/03/26 05:00
MHDA- 2004/04/20 05:00
CRDT- 2004/03/26 05:00
PHST- 2003/04/01 00:00 [received]
PHST- 2004/03/26 05:00 [pubmed]
PHST- 2004/04/20 05:00 [medline]
PHST- 2004/03/26 05:00 [entrez]
AID - S1665-2681(19)32144-1 [pii]
PST - ppublish
SO  - Ann Hepatol. 2003 Apr-Jun;2(2):69-75.