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Saturday, June 26, 2010

Defective Translocation of PKCε in EtOH-Induced Inhibition of Mg2+ Accumulation in Rat Hepatocytes


Rats chronically fed ethanol for 3 weeks presented a marked decreased in total hepatic Mg2+ content and required approximately 12 days to restore Mg2+ homeostasis upon ethanol withdrawal. This study was aimed at investigating the mechanisms responsible for the EtOH-induced delay.

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.

Hepatocytes from ethanol-fed rats presented a marked inhibition of Mg2+ accumulation and a defective translocation of PKCε to the cell membrane. Upon ethanol withdrawal, 12 days were necessary for PKCε translocation and Mg2+ 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 Mg2+ accumulation and PKCε translocation for more than 60 minutes. Also in this model, recovery of Mg2+ accumulation was associated with restoration of PKCε translocation. The use of specific antisense in HepG2 cells confirmed the involvement of PKCε in modulating Mg2+ accumulation.

Translocation of PKCε isoform to the hepatocyte membrane is essential for Mg2+ accumulation to occur. Both acute and chronic ethanol administrations inhibit Mg2+ accumulation by specifically altering PKCε translocation to the cell membrane.


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