High-density lipoprotein inhibits UDP-N-acetylgalactosamine:GM3, N-acetylgalactosaminyltransferase and differentiation of cultured cerebral cells: comparison with a formerly described inhibitor of this enzyme.

We have previously described a thermostable inhibitor of the UDP-N-acetylgalactosamine:GM3,N-acetylgalactosaminyltransferase (GM2 synthase) purified from chicken blood serum. Some properties of the GM2 synthase inhibitory preparation (IP) resemble those of high-density lipoprotein (HDL), i.e., both have a MW of 200,000 in native conditions and are resistant to denaturation by heat. These and other facts prompted us to test the possibility that lipoproteins regulate ganglioside biosynthesis in the CNS. For this purpose, serum lipoprotein fractions were isolated from chicken serum by flotation and were assayed as inhibitors of GM2 synthase activity and of neuron differentiation in culture. HDL (in contrast to fractions containing very low-density or low-density lipoprotein) inhibited GM2 synthase with the same specific activity as IP and inhibited neuron cell differentiation in culture in a similar way. Furthermore, these two preparations also share several other characteristics; i.e., both have the same cholesterol content, the same floating behavior on KBr gradients, and the same polypeptide pattern as detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and staining with Coomassie Blue, or after western blot and revealing with an antibody prepared against IP, which is able to diminish the inhibitory effect of this preparation. The results described indicate identity between HDL and IP and suggest that HDL (particularly apolipoprotein A) could play an important role on ganglioside biosynthesis modulation during CNS development. The antineuritogenic effect of HDL described in this study could be of physiological relevance during CNS development and response to injury.