Regulation of UDP‐Galactose:Ceramide Galactosyltransferase and UDP‐Glucose:Ceramide Glucosyltransferase After Crush and Transection Nerve Injury

Abstract: The enzyme activities of ceramide galactosyltransferase and ceramide glucosyltransferase were assayed as a function of time (0, 1, 2, 4, 7, 14, 21, 28, and 35 days) after crush injury or permanent transection of the adult rat sciatic nerve. These experimental models of neuropathy are characterized by the presence and absence of axonal regeneration and subsequent myelin assembly. Within the first 4 days after both injuries, a 50% reduction of ceramide galactosyltrans‐ferase‐specific activity was observed compared to values found in the normal adult nerve. This activity remained unchanged at 7 days after injury; however, by 14 days the ceramide galactosyltransferase activity diverged in the two models. The activity increased in the crushed nerve and reached control values by 21 days, whereas a further decrease was observed in the transected nerve such that the activity was nearly immeasurable by 35 days. In contrast, the ceramide glucosyltransferase activity showed a rapid increase between 1 and 4 days, followed by a plateau that was 3.4‐fold greater than that in the normal adult nerve, which persisted throughout the observation period in both the crush and transection models. [³H]Galactose precursor incorporation studies at 7, 14, 21, and 35 days after injury confirmed the previously observed shift in biosynthesis from the galactocerebrosides during myelin assembly in the crush model to the glucocere‐brosides and oligohexosylceramide homologues in the absence of myelin assembly in the transection model. The transected nerves were characterized by a peak of biosynthesis of the glucocerebrosides at 14 days. Of particular interest is the biosynthesis of the glucocerebrosides and the oligohexosyl‐ceramides at 7 and 14 days after crush injury. This biosynthesis was dramatically reduced by 21 days after crush, even though the ceramide glucosyltransferase activity remained elevated. The present data indicate that this shift in myelina‐tion‐dependent glycolipid biosynthesis is controlled at least partially at the level of these sugar transferases.