P-glycoprotein (ABCB1) but not multidrug resistance-associated protein 1 (ABCC1) is induced by doxorubicin in primary cultures of rat astrocytes.

摘要: At least two drug efflux pumps involved in multidrug resistance, P-glycoprotein (P-gp) and resistance-associated protein 1 (Mrp1), are expressed rat astrocyte primary cultures. The aim of this study was to compare the expression P-gp Mrp1 cultures exposed 50 or 500 ng/mL doxorubicin (DOX). Among genes rodents, mdr1a mdr1b, a time- dose-dependent increase mdr1b mRNA levels revealed by northern blot analysis. This up-regulation inhibited actinomycin D occurred as early 2 h after exposure DOX, whereas mrp1 transcripts were not modified DOX exposure. In addition, also strongly enhanced, manner, but expression. Moreover, raised cellular vincristine, substrate for both Mrp1. modulators PSC833 GW918, modulator MK571. On other hand, 24-h induced apoptosis astrocytes. Fumonisin B1, ceramide synthase inhibitor, reduced DOX-induced apoptosis, suggesting that de novo synthesis regulatory pathway might be apoptosis. western analysis showed fumonisin B1 able decrease overexpression DOX. Our results provide evidence up-regulates functional astrocytes cause via pathway.