Expression of the multidrug resistance P glycoprotein (Pgp) and multidrug resistance associated protein (MRP1) in Down syndrome brains

Transport by ATP-dependent efflux pumps such as P glycoprotein (Pgp) and mu ltidrug resistance associated protein (MRP), encoded by multidrug resistant (MDR) associated genes, is an increasingly recognized mechanism by which c ells maintain substrate homeostasis and evade drug therapy. Pgp and MRP are members of the so-called ATP binding cassette (ABC) transporters superfami ly, which are associated with many biological processes in both prokaryotes and eukaryotes, as well as clinical problems. The observation of upregulat ed sequences that are homologous to the Mycobacterium smegmatis phage resis tance (mpr) gene and putative ABC transporters subunits in fetal Down syndr ome (DS) using the gene hunting technique, subtractive hybridization formed the Rationale for this study. The expression of Pgp and MRP1 is therefore investigated in different brain regions of controls and adult DS patients w ith western blot technique. No apparent changes were observed between contr ols and DS in levels of Pgp in all brain regions examined. By contrast, MRP 1 detection using the rat monoclonal antibody (MRPr1) produced a significan t elevation in DS temporal cortex (P < 0.01) and parietal cortex (P < 0.05) . Although MRP1 detected with the mouse monoclonal antibody (MRPm6) tended to increase in most of the regions of DS brain, it failed to reach signific ance level. Age or postmortem interval did not correlate with protein level s in both controls as well as DS. Taken together, the current data provide evidence for the presence of MDR related pumps in different regions of the human brain. In addition, overexpression of MRP1 in DS brain may have some relevance to the disorder either by deranging substrate homeostasis or limi ting drug access.