Differential expression of guanine nucleotide-binding proteins enhances cAMP synthesis in regenerating rat liver
Autor: | Shiqi Yang, Anna Mae Diehl, Gary S. Wand, David Wolfgang |
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Rok vydání: | 1992 |
Předmět: |
Male
medicine.medical_specialty G protein Biology Adenylyl cyclase chemistry.chemical_compound GTP-Binding Proteins Internal medicine medicine Cyclic AMP Animals Hepatectomy Cells Cultured DNA synthesis Rats Inbred Strains General Medicine DNA Blotting Northern Liver regeneration Liver Regeneration Rats Kinetics medicine.anatomical_structure Endocrinology chemistry Liver Hepatocyte Phosphoenolpyruvate carboxykinase Glucagon receptor Cyclase activity Research Article |
Zdroj: | The Journal of clinical investigation. 89(6) |
ISSN: | 0021-9738 |
Popis: | Events leading to cAMP accumulation after partial hepatectomy (PH) and effects of cAMP on hormonal induction of DNA synthesis in hepatocytes were characterized. Hepatic cAMP peaked biphasically post-PH and paralleled changes in adenylyl cyclase activity. Fluctuations in cyclase activity were not explained by variations in glucagon receptor kinetics, but reflected altered G-protein expression. Membrane levels of the stimulatory G-protein, Gs alpha, increased early after PH and were sustained. Levels of the inhibitory G-protein, Gi2 alpha, increased more slowly, peaked later, and quickly fell. Levels of both G-proteins correlated poorly with levels of their mRNAs, suggesting posttranscriptional factors modify their membrane concentrations. When growth factor-induced DNA synthesis was compared in hepatocyte cultures grown with or without agents that increase intracellular cAMP, DNA synthesis was inhibited by sustained high levels of cAMP but was enhanced when high cAMP levels fell. In both regenerating liver and hepatocyte cultures, the expression of a "differentiated" hepatocyte gene, phosphoenolpyruvate carboxykinase, correlated with elevated cAMP levels. These data suggest that the differential expression of G-proteins integrates signals initiated by several growth factors so that the accumulation of cAMP is tightly regulated post-PH. The ensuing variations in cAMP levels modulate both growth and differentiated functions during liver regeneration. |
Databáze: | OpenAIRE |
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