Effect of chronic ethanol on apolipoprotein (Apo) E synthesis and glycosylation in rats.
We have previously shown in rats that chronic ethanol feeding significantly inhibits the incorporation of labeled leucine into Apo E secreted into the liver perfusate (p less than 0.01). Fish oil has been shown to counteract many of the adverse effects of ethanol. In order to explore whether this inhibitory effect of ethanol was due to the decreased synthesis and/or defective glycosylation of this glycoprotein, we have determined the effects of chronic ethanol and fish oil on the synthesis and glycosylation of Apo E in vivo. Four groups of male Wistar rats were pair-fed the following liquid diets for 8 weeks; (1) Ethanol Regular Fat, (2) Control Regular Fat, (3) Ethanol Fish Oil, and (4) Control Fish Oil. At the end, the rats were intraportally injected with a single dose of [U-14C]leucine (0.2 microCi/g body weight) and/or [2-3H]mannose (1 microCi/g body weight) and killed after 30 min. The incorporation of the labeled precursors into the immunoprecipitable Apo E was measured in the liver and its microsomal and Golgi fractions. The results showed marked decreases in mannose incorporation into total glycoproteins and specifically of Apo E in whole liver, microsomal, and Golgi fractions under ethanol treatment. In contrast, the leucine incorporation into liver Apo E increased 11% (p less than 0.048) by ethanol treatment. As a result, the [3H]mannose/[14C] leucine incorporation ratio also decreased 41% to 47% at the whole liver, microsomal, and Golgi fractions indicating a marked inhibition in glycosylation of Apo E in the ethanol group.(ABSTRACT TRUNCATED AT 250 WORDS)
Lipid Research Laboratory, V.A. Medical Center, Washington, DC 20422.
P
P
Ghosh
S J
SJ
Chirtel
M R
MR
Lakshman
D000437:Alcoholism / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001057:Apolipoproteins E / Q000096:biosynthesis / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D005395:Fish Oils / Q000494:pharmacology; D006031:Glycosylation / Q000187:drug effects; D006056:Golgi Apparatus / Q000187:drug effects; D007930:Leucine; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008358:Mannose; D008862:Microsomes, Liver / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D001057:Apolipoproteins E; D005395:Fish Oils; D007930:Leucine; D008358:Mannose