Overexpression of certain ABC proteins, among them the multidrug resistance associated protein
(MRP), contributes to drug resistance in organisms ranging from human neoplastic cells to parasitic protozoa. In the present study, the Plasmodium berghei mrp gene (pbmrp) was partially characterized and the predicted protein was classified using bioinformatics in order to explore its putative involvement in drug resistance.
Methods: The pbmrp gene from Selleck BMS-754807 the P. berghei drug sensitive, N clone, was sequenced using a PCR strategy. Classification and domain organization of pbMRP were determined with bioinformatics. The Plasmodium spp. MRPs were aligned and analysed to study their conserved motifs and organization. Gene copy number and organization were determined via Southern blot analysis in both N clone and the chloroquine selected line, RC. Chromosomal Southern blots and RNase protection assays were employed to determine the chromosomal location and expression levels of pbmrp in blood stages.
Results: The pbmrp gene is a single copy, intronless gene with a predicted open reading frame spanning
5820 nucleotides. Bioinformatic analyses show that this protein has distinctive features characteristic of the ABCC sub-family. Multiple sequence alignments reveal a high degree of conservation in the nucleotide binding and transmembrane domains within the MRPs from the Plasmodium spp. analysed. Expression of pbmrp was detected in asexual blood stages. Cilengitide manufacturer Gene organization, copy number and mRNA expression was similar in both lines studied. A chromosomal translocation was observed in the chloroquine selected RC line, from chromosome 13/14 to chromosome 8, when compared to the drug sensitive N clone.
Conclusion: In this study, the pbmrp gene was sequenced and classified as a member of the VX-770 ic50 ABCC subfamily. Multiple sequence alignments
reveal that this gene is homologous to the Plasmodium y. yoelii and Plasmodium knowlesi mrp, and the Plasmodium vivax and Plasmodium falciparum mrp2 genes. There were no differences in gene organization, copy number, or mRNA expression between N clone and the RC line, but a chromosomal translocation of pbmrp from chromosome 13/14 to chromosome 8 was detected in RC.”
“In the present study, the effects of baicalein were investigated on cervical cancer cell (U14)-bearing mice in vivo. By oral treatment with baicalein (30, 60 mg/kg body weight), the tumor growth inhibition percentage was 36.59 and 43.40%, and the increment percentage of survival time was 49.46 and 51.75%, respectively. Baicalein significantly induced apoptosis of tumor cells. Treatment with baicalein (30 mg/kg body weight) significantly decreased the expression of mutant p53 from 70.51 to 40.77%, increased the expression of Bax from 21.12 to 31.61%. Treatment with baicalein (60 mg/kg body weight) remarkably decreased the expression of mutant p53 to 44.13 from 70.51%, increased p19ARF to 16.63 from 10.85%, and Bax to 35.02 from 21.