Ethanol-induced effects on expression level, activity, and distribution of protein kinase C isoforms in rat liver Golgi apparatus.
Acute ethanol administration induces significant modifications both in secretive and formative membranes of rat liver Golgi apparatus. The decrease in glycolipoprotein secretion and their retention into the hepatocyte contribute to the pathogenesis of alcohol-induced fatty liver. Molecular and cellular mechanisms behind the ethanol-induced injury of the liver secretory pathway are not yet completely defined. In this study on intact livers from ethanol-treated rats, the involvement of the Golgi compartment in the impairment of hepatic glycolipoprotein secretion has been correlated with changes in the expression level, subcellular distribution and enzymatic activity of protein kinase C (PKC) isoforms. Acute ethanol exposure determined a translocation of classic PKCs and delta isoform from the cytosol to cis and trans Golgi membranes, the site of glycolipoprotein retention in the hepatic cell. A marked stimulation of cytosolic epsilon PKC activity was observed throughout the period of treatment. The presence of activated PKC isozymes at the Golgi compartment of alcohol-treated rat livers may play a role in hepatic secretion and protein accumulation. Direct and indirect effects of ethanol consumption on PKC isozymes and Golgi function are discussed.
Domenicotti
C
C
Department of Experimental Medicine, University of Genoa, Italy.
Paola
D
D
Vitali
A
A
Nitti
M
M
Cottalasso
D
D
Pronzato
M A
MA
Poli
G
G
Melloni
E
E
Marinari
U M
UM
D000818:Animals; D015153:Blotting, Western; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D000431:Ethanol / Q000494:pharmacology*; D006023:Glycoproteins / Q000378:metabolism; D006056:Golgi Apparatus / Q000187:drug effects* / Q000201:enzymology; D007425:Intracellular Membranes / Q000187:drug effects; D007527:Isoenzymes / Q000096:biosynthesis*; D008074:Lipoproteins / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D008297:Male; D011493:Protein Kinase C / Q000096:biosynthesis*; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D006023:Glycoproteins; D007527:Isoenzymes; D008074:Lipoproteins; D000431:Ethanol; C497260:Prkcd protein, rat; C497257:Prkce protein, rat; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon