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Defective Translocation of PKCε in EtOH‐Induced Inhibition of Mg 2+ Accumulation in Rat Hepatocytes
Author(s) -
Torres Lisa M.,
Konopnika Bocena,
BertiMattera Lilia.,
Liedtke Carole,
Romani Andrea
Publication year - 2010
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2010.01252.x
Subject(s) - chromosomal translocation , ethanol , protein kinase c , hepatocyte , chemistry , medicine , homeostasis , in vitro , endocrinology , biology , biochemistry , signal transduction , gene
Background: Rats chronically fed ethanol for 3 weeks presented a marked decreased in total hepatic Mg 2+ content and required approximately 12 days to restore Mg 2+ homeostasis upon ethanol withdrawal. This study was aimed at investigating the mechanisms responsible for the EtOH‐induced delay. Methods: Hepatocytes from rats fed ethanol for 3 weeks (Lieber‐De Carli diet—chronic model), rats re‐fed a control diet for varying periods of time following ethanol withdrawal, and age‐matched control rats fed a liquid or a pellet diet were used. As acute models, hepatocytes from control animals or HepG2 cells were exposed to varying doses of ethanol in vitro for 8 minutes. Results: Hepatocytes from ethanol‐fed rats presented a marked inhibition of Mg 2+ accumulation and a defective translocation of PKCε to the cell membrane. Upon ethanol withdrawal, 12 days were necessary for PKCε translocation and Mg 2+ accumulation to return to normal levels. Exposure of control hepatocytes or HepG2 cells to a dose of ethanol as low as 0.01% for 8 minutes was already sufficient to inhibit Mg 2+ accumulation and PKCε translocation for more than 60 minutes. Also in this model, recovery of Mg 2+ accumulation was associated with restoration of PKCε translocation. The use of specific antisense in HepG2 cells confirmed the involvement of PKCε in modulating Mg 2+ accumulation. Conclusions: Translocation of PKCε isoform to the hepatocyte membrane is essential for Mg 2+ accumulation to occur. Both acute and chronic ethanol administrations inhibit Mg 2+ accumulation by specifically altering PKCε translocation to the cell membrane.