Hepatopoietin——A Non-classical Secretory Protein

Hepatopoietin (HPO) could be secreted by the cultured hepatocytes.Unlike classical secretory proteins, HPO lacks a typical signal sequence which allows the transfer of the protein across the membrane of endoplastic reticulum(ER). Western blot analysis indicated that HPO was secreted by the hepatoma cells as a dimmer. Brefeldin A and monensin did not inhibit the secretion of HPO. This demonstrated that the secretion of HPO did not follow the ER-Golgi patheway. Glyburide could block the secretion of non-classical secretory protein IL-1β through ABC1 transporter pathway,but did not inhibit the secretion of HPO from hepatoma cells. This suggested that the ABC1 transporter was not involved in the secretion of HPO. On the other hand, DNP and NH-4Cl did not increase the secretion of HPO either.This meant that endosome and lysosome-related vesicles were not concerned with the secretion of HPO. Taken together, it can be concluded that HPO was a non-classical secretory protein released through a novel secretory pathway.