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Very low protein diets induce a rapid decrease in hepatic cAMP-dependent protein kinase followed by a lower increase
1Department of Nutritional Sciences, University of Guelph, Ontario, Canada.
The Journal of Nutrition
|July 1, 1996
Summary
Malnutrition rapidly decreases liver protein kinase A (PKA) activity, an early response. Later, molecular changes increase cyclic AMP (cAMP) production, potentially to maintain essential functions during low protein intake.
Area of Science:
- Biochemistry
- Cellular Biology
- Nutritional Science
Background:
- Malnutrition is linked to desensitized cAMP-mediated responses in the liver.
- Receptor-stimulated cAMP production increases in hepatocytes from malnourished rats, yet cAMP-dependent protein kinase (PKA) activity decreases.
Purpose of the Study:
- To investigate the time course of cAMP-mediated response desensitization in the liver during malnutrition.
- To elucidate the molecular mechanisms underlying altered cAMP signaling in malnourished hepatocytes.
Main Methods:
- Weanling rats were fed either a 0.5% (malnourished) or 15% protein (control) diet for 1, 3, 7, or 14 days.
- Assessed PKA activity, regulatory subunit quantities (RI and RII), and adenylyl cyclase activities (basal, stimulated by MnCl2, and G-protein).
- Investigated the role of PKA phosphorylation and alkaline phosphatase treatment on adenylyl cyclase activity.
Main Results:
- Total PKA activity decreased significantly after 3 days of a low-protein diet, localized to the cytosol and linked to reduced RI subunit quantity.
- Adenylyl cyclase activities increased only after 2 weeks of malnutrition, associated with increased stimulatory G-protein quantity.
- PKA phosphorylation and alkaline phosphatase treatment did not explain the increased adenylyl cyclase activity in malnourished rats.
Conclusions:
- Loss of PKA activity is an early adaptation to low protein diets.
- Subsequent molecular adaptations increase cAMP production, potentially serving as adaptive responses to maintain essential cAMP-dependent functions during malnutrition.