| First Author | Singhal SS | Year | 2008 |
| Journal | FEBS Lett | Volume | 582 |
| Issue | 23-24 | Pages | 3408-14 |
| PubMed ID | 18789326 | Mgi Jnum | J:141242 |
| Mgi Id | MGI:3817807 | Doi | 10.1016/j.febslet.2008.09.001 |
| Citation | Singhal SS, et al. (2008) Diminished drug transport and augmented radiation sensitivity caused by loss of RLIP76. FEBS Lett 582(23-24):3408-14 |
| abstractText | This study was undertaken to characterize the consequences of Ral-interacting protein (RLIP76)-loss with respect to drug resistance, transport, radiation resistance, and alternative transport mechanisms in mouse embryonic fibroblasts (MEFs). MEFs were derived from RLIP76+/+, RLIP76+/- and RLIP76-/- mice. The transport of doxorubicin (DOX), colchicine (COL), leukotriene C4 and dinitrophenyl S-glutathione (DNP-SG) was analyzed in inside-out vesicles (IOVs) prepared from MEFs. We used immuno-titration of transport activity to determine the contribution of RLIP76, MRP1, and p-glycoprotein (Pgp) towards total transport activity. Loss of RLIP76 alleles resulted in significant sensitization to radiation, DOX, cisplatin, and vinorelbine (VRL). In IOVs prepared from MEFs, we observed a stepwise loss of transport activity. Loss of RLIP76 confers sensitivity to xenobiotics and radiation due to the loss of a common transport mechanism for glutathione-electrophile conjugates and xenobiotics. |
