Overexpression of protein disulfide isomerase-like protein in a mouse leukemia L1210 cell lineselected for resistance to 4-methyl-5-amino-l-formylisoquinoline thiosemicarbazone, aribonucleotide reductase inhibitor

摘要

A mouse leukemia L1210 cell line selected for resistance to the potent ribonucleotide reductase inhibitor, 4-methyl-5-amino-l-formylisoquinoline thiose-micarbazone (MAIQ) in addition to showing alterations at the ribonucleotide reductase site, shows multiple metabolic alterations that are not overtly related to ribonucleotide reductase. This MAIQ-resistant L1210 cell line (MQ-580) expresses high levels of a "new" protein (P5) that we have identified as a member of the protein disulfide isomerase family of proteins (P5). Supporting the high expression of P5 in the MQ-580 cells is gene amplification of the P5 gene with increased mRNA levels for P5. A hydroxyurea-resistant L1210 cell line does not express the P5 protein. The MQ-580 cells showed increased levels of thiol-containing proteins on the cell surface relative to the levels seen on the plasma membranes of wild-type and hydroxyurea-resistant cells. It is possible that the overexpression of P5, a member of the protein disulfide isomerase familyof proteins contributes to the multi-factorial mechanisms of drug resistance seen in the MAIQ-580 L1210 cells.