Transport of heparan sulfate into the nuclei of hepatocytes

A rat hepatocyte cell line which accumulates free heparan sulfate (HS) chains enriched in GlcA-2-SO4 residues in the nucleus was labeled with 35SO42- and the rate of appearance of [35SO4]HS in the nucleus was measured. [35SO4]HS began to accumulate in the nucleus 2 h after the addition of 35SO42- and reached a steady state level after 20 h. HS was lost from the nuclei of prelabeled cells with a t/sub 1/2/ of 8 h. Chloroquine did not inhibit the transport of HS into the nucleus, but increased the t/sub 1/2/ for the exit of HS from the nucleus to 20 h. At both 370C and 160C exogenous [35SO4]proteoHS was taken up by the cells and converted to free chains and about 10% of the internalized [35SO4]HS was transported into the nucleus. The [35SO4]HS isolated from the nucleus was enriched in GlcA-2-SO4 residues, whereas the [35SO4]HS remaining in the rest of the intra-cellular pool showed a corresponding depletion in GlcA-2-SO4 residues. The results show that nuclear HS is derived from the pool of a secreted proteoHS and that metabolism of exogenous HS by hepatocytes does not involve lysosomal processing of the internalized HS