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A possible role for multidrug resistance-associated protein in the secretion of basic fibroblast growth factor by
1Division of Basic and Clinical Immunology, University of California, Irvine, CA 92697, USA.
Abstract:
Basic fibroblast growth factor (bFGF) lacks signal sequence and therefore the mechanism of its secretion is unknown. Multidrug resistance-associated protein (MRP) has been shown to transport a variety of molecules. Therefore, in this study we examined the role of MRP in the secretion of bFGF by osteogenic sarcoma MG-63 cells which spontaneously secrete bFGF. We show that MG-63 cells express MRP both at the protein and at the mRNA level. Furthermore, probenecid (a putative inhibitor of transport activity of MRP), in a concentration-dependent manner, inhibited secretion of bFGF from MG-63 cells with concomitant increase in intracellular contents of bFGF. These results suggest that MRP may have a possible role in the secretion of bFGF.
Insights
The multidrug resistance-associated protein (MRP) may facilitate the secretion of basic fibroblast growth factor (bFGF) from osteogenic sarcoma cells. Inhibiting MRP reduced bFGF secretion, suggesting a role in its transport.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Basic fibroblast growth factor (bFGF) is crucial for cell growth and differentiation.
- The secretion mechanism for bFGF is not well understood due to the absence of a signal sequence.
- Multidrug resistance-associated proteins (MRPs) are known transporters of various molecules.
Purpose of the Study:
- To investigate the potential role of MRP in the secretion of bFGF.
- To determine if osteogenic sarcoma MG-63 cells express MRP and if it influences bFGF secretion.
Main Methods:
- MG-63 cells, known to secrete bFGF, were analyzed for MRP expression at the protein and mRNA levels.
- The effect of probenecid, an MRP inhibitor, on bFGF secretion was assessed.
- Intracellular bFGF levels were measured in the presence of probenecid.
Main Results:
- MG-63 cells were confirmed to express MRP at both the protein and mRNA levels.
- Probenecid treatment inhibited bFGF secretion in a concentration-dependent manner.
- Inhibition of secretion by probenecid led to an increased intracellular accumulation of bFGF.
Conclusions:
- The findings suggest that MRP plays a role in the secretion of bFGF from MG-63 cells.
- MRP may function as a transporter for bFGF, explaining its non-classical secretion pathway.