1,2-sn-diacylglycerol accumulates in choline-deficient liver. A possible mechanism of hepatic carcinogenesis via alteration in protein kinase C activity?
Choline deficiency is associated with triacylglycerol accumulation in the liver, and is the only nutritional state known to trigger hepatic cancer spontaneously. In two different experiments, rats were pair-fed for 6 weeks with control (0.2% choline), or choline-deficient (CD) (0.002% choline) diets. Hepatic choline and phosphocholine declined in CD animals to 54% and 16% of control levels, respectively. In control livers, 1,2-sn-diacylglycerol (1,2-sn-DAG) concentration was (in nmol/g wet wt) 144 (+/- 25; mean +/- SE); while in CD livers it was 792 (+/- 140) in the first experiment. In the second experiment the values were 375 (+/- 26) and 1147 (+/- 74), respectively. 1,2-sn-DAG, a precursor of triacylglycerol, is an endogenous activator of protein kinase C (PKC). PKC is the presumed site of action of the tumor-promoting phorbol esters. We suggest that the 1,2-sn-DAG accumulating in CD liver could bind PKC, altering its activity, and thus contribute to the carcinogenic effect of CD diets.
Blusztajn
J K
JK
Department of Pathology, Boston University School of Medicine, MA 02118.
Zeisel
S H
SH
D000818:Animals; D002273:Carcinogens / Q000378:metabolism; D002794:Choline / Q000378:metabolism; D002796:Choline Deficiency / Q000378:metabolism*; D004075:Diglycerides / Q000378:metabolism*; D004789:Enzyme Activation; D005989:Glycerides / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms / Q000209:etiology* / Q000378:metabolism; D008297:Male; D010767:Phosphorylcholine / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
C011439:1,2-diacylglycerol; D002273:Carcinogens; D004075:Diglycerides; D005989:Glycerides; D010767:Phosphorylcholine; D011493:Protein Kinase C; D002794:Choline