Differences in susceptibility of rat liver and brain sialidases to ethanol and gangliosides.
Based on reports that ethanol can decrease the level of sialic acid (SA) (neuraminic acid) in several tissues, we tested the hypothesis that ethanol promotes SA cleavage by enhancing the activity of sialidases (neuraminidases). We also investigated whether brain and liver sialidases have the same response to ethanol and gangliosides, especially since our prior studies have demonstrated that gangliosides could antagonize ethanol-induced behavior. Experiments were conducted on homogenates of brain and liver and of liver slices of adult rats. In liver slices, cleavage of SA did not fall in proportion to the ethanol-induced inhibition of sialidase; in fact, at 0.1 M ethanol, free SA increased, even though sialidase was inhibited. Brain sialidase activity on endogenous sialoglycoconjugates was much more resistant to ethanol than liver sialidase and was fully active even in concentrations as high as 1 M. When gangliosides were incubated with liver slices in the absence of ethanol, sialidase was markedly stimulated. The ethanol-induced inhibition of sialdase in liver slices was mimicked by sorbitol, suggesting that the inhibition may be caused by a shift in redox state as a result of increased NADH. The ethanol metabolite, acetaldehyde, does not seem to be a factor, because sialidase inhibition still occurred when slices were incubated with ethanol containing pyrazole. The results indicate that ethanol promotes the accumulation of free SA in liver without stimulating sialdase; our other work suggests that the cause is an increase in accessibility to sialoglycoconjugates rather than decreased utilization of SA. Brain and liver sialidases clearly respond differently to both ethanol and gangliosides.
Mathew
J
J
Department of Veterinary Anatomy, Texas A & M University, College Station 77843.
Klemm
W R
WR
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D005732:Gangliosides / Q000494:pharmacology*; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D009439:Neuraminidase / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012794:Sialic Acids / Q000378:metabolism*; D013012:Sorbitol / Q000494:pharmacology
D005732:Gangliosides; D011720:Pyrazoles; D012794:Sialic Acids; D000431:Ethanol; D013012:Sorbitol; D009439:Neuraminidase