[Study of the binding of nuclear proteins from Plasmodium berghei strains with different chloroquine sensitivity to oligonucleotides corresponding to regulatory elements of multidrug resistance (mdr1) gene].
Using electrophoretic mobility shift assay we first revealed in the nuclear extracts of the rodent malaria parasite Plasmodium berghei (P. berghei) proteins, which bind specifically to the double-stranded oligonucleotides reproducing the binding sites of the transcription factors of AP1 family, NF-IL6 and SP1 involved in the up-regulation of human multidrug resistance (mdr1) gene and to the oligonucleotide corresponding to the element responsive for the stimulation by serum (SRE). The nuclear proteins isolated from the P. berghei strains with various chloroquine sensitivity bound differently to the most of the oligonucleotide probes used. Mutations in the consensus sequences of AP1, NF-IL6 and SRE led to the loss of some DNA-protein complexes, suggesting the existence of malaria parasite nuclear proteins, whose DNA-binding domains are similar to DNA-binding domains of NF-IL6, SRF1, and AP1 family members. These proteins exhibit greater activities in chloroquine resistant strains. The results obtained denote profound alterations in the plasmodium regulatory apparatus occurred as the result of selection on chloroquine resistance.
Pankova
T G
TG
Igonina
T M
TM
Kobzev
V F
VF
Merkulova
T I
TI
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology; D002738:Chloroquine / Q000494:pharmacology; D016384:Consensus Sequence; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D004351:Drug Resistance / Q000235:genetics*; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D009154:Mutation; D009687:Nuclear Proteins / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D009841:Oligonucleotides / Q000737:chemistry; D010962:Plasmodium berghei / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D015800:Protozoan Proteins / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D050436:Regulatory Elements, Transcriptional / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000962:Antimalarials; D009687:Nuclear Proteins; D009841:Oligonucleotides; D015800:Protozoan Proteins; D014157:Transcription Factors; D002738:Chloroquine; D004247:DNA