Regulation of the human asialoglycoprotein receptor by cAMP

The mechanism of regulated expression of the asialoglycoprotein receptor (ASGR) by cAMP was investigated in the human hepatoblastoma cell line, HepG2. Incubation of HepG2 cells with the cell-permeant 8-bromo-cAMP or induction of intracellular cAMP with forskolin reduced receptor expression in confluent HepG2 cultures. Immunoblot analysis established that this reduction of receptor activity was due to a reduction of expression of both ASGR subunit polypeptides H1 and H2. Estimates of the steady-state levels of H1- and H2-related mRNA by Northern blot analysis indicated that reduced ASGR expression was a result of a decrease in gene transcript number. By a combination of run-on and mRNA turnover studies, it was suggested that this reduction of ASGR-related mRNA resulted from its destabilization induced by 8-bromo-cAMP. The effect of 8-bromo-cAMP appears not to be limited to ASGR expression as a rapid reduction in the albumin mRNA was also observed. In contrast, both the beta-actin and glyceraldehyde-3-phosphate dehydrogenase mRNA levels were elevated by exposure to 8-bromo-cAMP.