Up-regulation of the low density lipoprotein receptor-related protein by dexamethasone in HepG2 cells.
Dexamethasone has been shown to decrease the expression of the low density lipoprotein (LDL) receptor, but its effect on other members of the LDL receptor family is not known. We studied the effect of dexamethasone in HepG2 cells on the expression of the LDL receptor family members using radiolabeled receptor associated protein (RAP) which binds to all the members of the family. Treatment of HepG2 cells with increasing concentrations of dexamethasone resulted in a 2-fold increase in the binding and degradation of RAP. To identify the receptor responsible for the increased binding and degradation of RAP, we used specific ligands. For LDL receptor, we used LDL itself. For the LDL receptor-related protein/alpha 2-macroglobulin receptor, we used activated alpha 2-macroglobulin. The binding of LDL to HepG2 cells was decreased, whereas binding and degradation of activated alpha 2-macroglobulin was increased by 2-fold suggesting that dexamethasone increased LRP expression. Increased LRP expression was positively correlated with the increase in the steady-state levels and transcript numbers of the LRP mRNA; no changes in RAP or gamma-actin mRNA levels were observed. Increased mRNA levels were not due to an increased rate of transcription of the gene as assessed by nuclear run-on experiments. These studies indicate that dexamethasone increases cell-surface LRP activity in HepG2 cells by increasing the steady state mRNA levels and suggest that post-transcriptional mechanisms play a role in controlling LRP mRNA levels.
Kancha
R K
RK
Department of Pathology, Medical College of Pennsylvania, Philadelphia, USA.
Hussain
M M
MM
D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D012333:RNA, Messenger / Q000378:metabolism; D011971:Receptors, Immunologic / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011973:Receptors, LDL / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects*; D000511:alpha-Macroglobulins / Q000378:metabolism
D026503:Low Density Lipoprotein Receptor-Related Protein-1; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D011973:Receptors, LDL; D000511:alpha-Macroglobulins; D003907:Dexamethasone