Related Experiment Videos
Second messenger modulation of the asialoglycoprotein receptor
1Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461.
The Journal of Biological Chemistry
|February 5, 1990
Summary
Cyclic guanosine monophosphate (cGMP) increases the expression of the asialoglycoprotein receptor (ASGR) in liver cells. This finding suggests a balance between cGMP and cyclic adenosine monophosphate (cAMP) is crucial for maintaining liver cell function.
Area of Science:
- Hepatology
- Molecular Biology
- Cellular Signaling
Background:
- Post-transcriptional regulation of the asialoglycoprotein receptor (ASGR) in HepG2 cells is influenced by biotin.
- Biotin's induction of intracellular cyclic guanosine monophosphate (cGMP) may affect ASGR expression.
Purpose of the Study:
- To investigate if cGMP induction affects ASGR expression in HepG2 cells.
- To explore the role of cGMP and cyclic adenosine monophosphate (cAMP) in maintaining differentiated liver cell functions.
Main Methods:
- HepG2 cells were cultured in biotin-depleted medium with 8-bromo-cGMP (8-Br-cGMP).
- ASGR expression and endocytosis rates were measured using iodinated asialoorosomucoid (125I-ASOR) binding assays.
- ASGR levels were assessed via transblot analysis and metabolic labeling followed by immunoprecipitation.
- Responses were compared to atrial natriuretic factor (ANF) induction and 8-bromo-cAMP (8-Br-cAMP) treatment.
Main Results:
- 8-Br-cGMP significantly increased both cell-surface and total ASGR binding and ASGR-mediated endocytosis in a dose-dependent manner.
- Transblot and metabolic labeling confirmed increased ASGR expression upon 8-Br-cGMP addition within 30 minutes.
- ANF induction of cGMP also enhanced ASGR metabolic labeling.
- HuH-7 cells showed similar responses to 8-Br-cGMP, while 8-Br-cAMP reduced ASGR expression.
Conclusions:
- Intracellular cGMP levels positively regulate ASGR expression and function in hepatocytes.
- cGMP and cAMP exhibit antagonistic roles in regulating ASGR expression, suggesting a critical balance for maintaining differentiated hepatocyte functions.