Regulation of liver cell ganglioside composition by extracellular fluid viscosity

The viscosity of plasma and extracellular fluid has been shown to be a regulator of lipoprotein production both in cultured hepatocytes and in vivo. The possibility that this extracellular effect on cell function involves modulation of cell surface membrane components was examined. In the present work, we studied the effect of medium viscosity on liver cell gangliosides known to be involved in various membrane functions and to be located predominantly at the cell surface membrane. Cultivation of isolated hepatocytes as primary cultures markedly reduced the ganglioside content, but this reduction process was attenuated by increasing the viscosity of the culture medium. Elevation of extracellular fluid viscosity inhibited the degradation of the cell gangliosides and secretion of lysosomal enzymes involved in ganglioside degradation. The cellular activity of these enzymes as well as the activity of enzymes involved in ganglioside synthesis, CMP-NANA:GM₁ sialyltransferase, CMP-NANAP:GM₃ sialyltransferase and UDP-galactose:GD₂ galactosyltransferase, were not affected bymodulation of the extracellular medium viscosity. It is proposed that the modulation of cell ganglioside content by extracellular fluid viscosity is due to an effect on enzymes involved in ganglioside catabolism.