Chronic ethanol feeding controls the activities of various sialidases by regulating their relative synthetic rates in the rat liver

We have determined the concentration effects of feeding for 8 weeks 10.8%, 21.6%, and 36% dietary ethanol calories on the activities and relative synthetic rates (RSRs) of various subcellular sialidases of rat liver. The hepatic RSRs of each species of sialidase was determined based on the ratio of 1-hour incorporation of [S-35]-methionine into immunoprecipitable sialidase as percent of the incorporation into total protein in each subcellular fraction. Ganglioside sialidase activities in the hepatic subcellular fractions were also determined. Ethanol feeding at 36% dietary calories caused an increase in the ganglioside sialidase activity of the plasma membrane sialidase (PMS) by 232% (P<.01) and that of cytosolic sialidase (CS) by 184% (P<.05), but decreased the lysosomal membrane sialidase (LMS) by 54% (P<.01) when compared with the control animals. The specificity of each antisialidase antibody was verified by immunoblots. The RSR of PMS was increased by 40% (P<.01), 67% (P<.01), and 220% (P<.01) in the 10.8%, 21.6%, and 36% ethanol groups, respectively. Similarly, the RSR of CS was increased by 17% (P<.01), 19% (P<.01), and 63% (P<.01), respectively, in these ethanol groups. In contrast, the RSR of LMS was inhibited by 36% (P<.01), 34% (P<.01), and 69% (P<.01), respectively, in these ethanol groups. Intralysosomal sialidase failed to hydrolyze gangliosides. Thus, PMS and CS, but not LMS or intralysosomal sialidase, may play important roles in ethanol-modulated desialylation of gangliosides and consequent liver injury and behavioral alterations. (C) 2005 Elsevier Inc. All rights reserved.