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Glucose starvation reduces IGF-I mRNA in tumor cells: evidence for an effect on mRNA stability
1Department of Biochemistry, University of Texas Health Science Center at San Antonio, 7730 Floyd Curl Drive, San Antonio, Texas 78284-7760, USA.
Abstract:
The purpose of this study was to characterize the mechanisms by which glucose regulates IGF-I gene expression in rat C6 glioma cells and in rat GH3 pituitary adenoma cells. Glucose starvation for periods of 12 to 48 h decreased IGF-I mRNA levels. In contrast, there was no stimulation of IGF-I mRNA by medium glucose between 1 and 25 mM over a 24-h period. Studies with hexoses and glycolytic metabolites suggested that glucose metabolism was required to maintain IGF-I mRNA. Glucose starvation lowered IGF-I mRNA half-life in both C6 and GH3 cells. Protein synthesis inhibition lowered IGF-I mRNA by about 20% in glucose-fed C6 and GH3 cells, while potently increasing IGF-I mRNA in glucose-starved C6 cells and not altering IGF-I mRNA in glucose-starved GH3 cells. Our results suggest that in these tumor cells, IGF-I mRNA stability is reduced by glucose starvation, secondary to a deficiency in intracellular glucose metabolism. Ongoing protein synthesis is not required for this mRNA de-stabilizing effect in GH3 cells. Rather, in glucose-starved C6 cells, decreased IGF-I mRNA stability may result from the action of a labile protein.
Insights
Glucose starvation reduces Insulin-like Growth Factor-I (IGF-I) mRNA stability in tumor cells. This decrease is linked to impaired glucose metabolism and may involve specific protein actions in certain cell types.
Area of Science:
- Molecular Endocrinology
- Cancer Biology
- Cellular Metabolism
Background:
- Insulin-like Growth Factor-I (IGF-I) plays a crucial role in cell growth and differentiation.
- Tumor cells often exhibit altered metabolic pathways, potentially impacting gene expression.
- The regulation of IGF-I gene expression by cellular glucose metabolism is not fully understood.
Purpose of the Study:
- To investigate the mechanisms by which glucose availability influences IGF-I gene expression.
- To characterize the role of glucose metabolism in maintaining IGF-I mRNA stability.
- To examine the impact of glucose starvation on IGF-I mRNA half-life in specific tumor cell lines.
Main Methods:
- Utilized rat C6 glioma and GH3 pituitary adenoma cells.
- Manipulated glucose concentrations and employed hexoses/metabolites to assess glucose metabolism.
- Measured IGF-I mRNA levels and half-life under varying glucose conditions and protein synthesis inhibition.
Main Results:
- Glucose starvation significantly decreased IGF-I mRNA levels and reduced mRNA half-life in both cell types.
- Glucose metabolism, not just glucose presence, was essential for maintaining IGF-I mRNA levels.
- Protein synthesis inhibition differentially affected IGF-I mRNA stability, suggesting cell-specific regulatory mechanisms.
Conclusions:
- Glucose starvation destabilizes IGF-I mRNA in tumor cells, primarily due to impaired intracellular glucose metabolism.
- The observed decrease in IGF-I mRNA stability is independent of ongoing protein synthesis in GH3 cells.
- A labile protein may contribute to decreased IGF-I mRNA stability in glucose-starved C6 cells.