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Peptide transport by the multidrug resistance pump
R C Sharma1, S Inoue, J Roitelman
1Department of Biological Sciences, Stanford University, California 94305-5020.
The Journal of Biological Chemistry
|March 25, 1992
Summary
Multidrug resistance P-glycoprotein (P170) transports peptides, not just drugs. This finding suggests P170 and similar proteins may secrete cellular peptides, impacting drug resistance and cellular functions.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- P-glycoprotein (P170) is an ATP-hydrolyzing transmembrane pump.
- Elevated P170 levels confer resistance to chemotherapeutic agents in mammalian cells.
- P170's function is proposed to protect against dietary toxins.
Purpose of the Study:
- To investigate the transport capabilities of P170 beyond chemotherapeutic agents.
- To explore the role of the multidrug resistance gene (mdr1) in peptide transport.
- To determine if P170 mediates resistance to synthetic peptides.
Main Methods:
- Selected a Chinese hamster ovary cell line for resistance to N-acetyl-leucyl-leucyl-norleucinal (ALLN).
- Analyzed ALLN-resistant variants for multidrug resistance (MDR) phenotype, including mdr1 gene expression and amplification.
- Utilized a mouse embryo cell line overexpressing the mdr1 gene.
Main Results:
- The ALLN-resistant variant exhibited the classical MDR phenotype, with mdr1 gene overexpression and amplification.
- The mouse embryo cell line overexpressing mdr1 was also resistant to ALLN.
- Demonstrated that P170 is capable of transporting peptides.
Conclusions:
- P-glycoprotein (P170) can transport peptides, expanding its known function.
- The mdr1 gene product may be involved in the secretion of cellular peptides.
- MDR-like genes in mammalian cells could play a role in peptide secretion, similar to bacterial and yeast homologs.