Interaction of multidrug-resistant Chinese hamster ovary cells with amphiphiles

Loe, DW; Sharom, FJ

doi:10.1038/bjc.1993.338

Cited by 45 publications

(41 citation statements)

References 40 publications

(41 reference statements)

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“…The difference between NP30 activities against these isolates can-not be explained by point mutations in Pfcrt and Pfmdr1, since these mutations are present in all the parasites used in the study. In addition, only poor interactions have been identified between mammalian P glycoproteins and long-chain NPEs [193].…”

Section: Phenothiazines (Antipsychotic Drugs) (Table 4)mentioning

confidence: 99%

Chloroquine Resistance Reversal Agents as Promising Antimalarial Drugs

Henry¹,

Alibert²,

Orlandi-Pradines³

et al. 2006

CDT

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The development and spread of resistance to antimalarial drugs poses a severe and increasing public health threat. Failures of prophylaxis or treatment with quinolines, hydroxynaphthoquinones, sesquiterpene lactones, antifolate drugs and sulfamides are involved in a return malaria-related morbidity and mortality. Resistance is associated with a decrease in accumulation of drugs into the vacuole, which results from a reduced uptake of the drug, an increased efflux or a combination of both. A number of candidate genes in P. falciparum have been proposed to be involved in antimalarial resistance, each concerned in membrane transport. Weaker or stronger associations are seen in P. falciparum between the resistance to quinolines or artemisinin derivatives and codon changes in Pfmdr1, a gene which encodes Pgh-1, an ortholog of one of the P-glycoproteins expressed in multi-drug resistant human cancer cells (ABC transporter). Further analysis has revealed a new gene, Pfcrt, encoding a PfCRT protein, which resembles an anion channel. Codon changes found in the Pfcrt sequence in drug resistant isolates could facilitate the drug efflux through a putative channel. It has been proposed that the reversal of quinoline resistance by verapamil is due to hydrophobic binding to the mutated PfCRT protein. Several compounds have demonstrated in the past decade a promising capability to reverse the antimalarial drug resistance in vitro in parasite isolates, in animal models and in human malaria. These drugs belong to different pharmacological classes such as calcium channel blockers, tricyclic antidepressants, antipsychotic calmodulin antagonists, histamine H1-receptor antagonists, analgesic and antipyretic drugs, non-steroidal anti-inflammatory drugs, and to different chemical classes such as synthetic surfactants, alkaloids from plants used in traditional medicine, pyrrolidinoaminoalkanes and anthracenic derivatives. Here we summarize the progress made in biochemical and genetic basis of antimalarial resistance, emphasizing the recent developments on drugs, which interfere with trans membrane proteins involved in drug efflux or uptake.

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Section: Phenothiazines (Antipsychotic Drugs) (Table 4)mentioning

confidence: 99%

Chloroquine Resistance Reversal Agents as Promising Antimalarial Drugs

Henry¹,

Alibert²,

Orlandi-Pradines³

et al. 2006

CDT

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“…The MDR Chinese hamster ovary cell line CH R B30 [26] was grown as described previously [27,28]. Plasma membrane vesicles were isolated from the MDR cells using nitrogen cavitation [29,30] and stored at Ϫ70°C for no longer than 3 months before use.…”

Section: Methodsmentioning

confidence: 99%

The ATPase and ATP‐binding functions of P‐glycoprotein

Romsicki

Sharom

1998

European Journal of Biochemistry

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P-glycoprotein functions as an active efflux pump for lipophilic compounds and plays an important role in the resistance of human cancers to chemotherapeutic drugs. Drug transport is powered by ATP hydrolysis at two highly conserved nucleotide-binding domains, which are proposed to be located at the cytosolic face of the protein. The ATPase activity of P-glycoprotein depends on the presence of phospholipids, and various lipids affect both basal ATPase activity and its stimulation or inhibition by drug substrates. The modulating effects of the lipid-phase state and effects on the function of the nucleotidebinding domains of P-glycoprotein have been studied in reconstituted vesicles of the synthetic phospholipids 1-palmitoyl-2-myristoylphosphatidylcholine (PamMyrGroPCho) and dimyristoylphosphatidylcholine (Myr 2GroPCho). The kinetic parameters for P-glycoprotein ATPase activity were determined, and a fluorescence-quenching technique was used to measure the K d for ATP binding. The values of both the K m for ATP hydrolysis and K d for ATP binding were significantly different above and below the gel/liquidcrystalline phase transition temperature (t m) of PamMyrGroPCho and Myr2GroPCho, whereas they were similar at the same temperatures for P-glycoprotein in detergent solution. A discontinuity at 21Ϫ24°C was observed in the Arrhenius plots of P-glycoprotein ATPase activity in a membrane environment, but not in detergent solution. In addition, the activation energies for ATP hydrolysis in the gel and liquidcrystalline phases of the lipid bilayer were significantly different. P-glycoprotein in PamMyrGroPCho bilayers displayed an unusually low activation energy just below the melting transition. These results indicate that both ATP binding and ATP hydrolysis by P-glycoprotein are affected by the phase state of the host lipids in which it is reconstituted. Lipids may modulate the function of the nucleotide-binding domains of P-glycoprotein by interacting with the transmembrane regions of the protein, or the nucleotidebinding domains themselves may interact with the surface of the bilayer.

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“…The difference between the NP30 activities against these isolates can not be explained by point mutations in Pfcrt and Pfmdr1, since these mutations are present in all the parasites used in the study. In addition, only poor interactions have been identified between mammalian P glycoproteins and long-chain NPEs [307].…”

Section: -Transporter Inhibitors and Modulators Of The Multidrug Resimentioning

confidence: 99%

Chemosensitizers in Drug Transport Mechanisms Involved in Protozoan Resistance

Pradines

Pages²,

Barbe³

2005

CDTID

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The emergence and spread of antiparasitic drug resistance pose a severe and increasing public health threat. Failures in prophylaxis or those in treatment with quinolines, hydroxynaphtoquinones, sesquiterpenic lactones, antifolate drugs, arsenic and antimony containing drugs sulfamides induce reemergence of parasitic-related morbidity and mortality. Resistance is often associated with alteration of drug accumulation into parasites, which results from a reduced uptake of the drug, an increased efflux or, a combination of the two processes. Resistance to quinolines, artemisinin derivatives and arsenicals and expression of an active efflux mechanism are more or less correlated in protozoa like Plasmodium spp., Leishmania spp., and Trypanosoma spp. Various parasite candidate genes have been proposed to be involved in drug resistance, each concerned in membrane transport. Genes encoding membrane glycoproteins, orthologue to the P-glycoproteins identified in MDR human cancer cells, have been described in these resistant pathogens in addition to various membrane proteins involved in drug transport. Several compounds have demonstrated, in the past decade, promising capability to reverse the drug resistance in parasite isolates in vitro, in animal models and for human malaria. These drugs belong to different pharmacological classes such as calcium channel blockers, tricyclic antidepressants, antipsychotic calmodulin antagonists, histamine H1-receptor antagonists, analgesic antipyretic drugs, non-steroidal anti-inflammatory drugs, and to different chemical classes such as synthetic surfactants, alkaloids from plants used in traditional medicine, pyrrolidinoaminoalkanes and derivatives, and anthracene derivatives. Here, are summarized the molecular bases of antiparasitic resistance emphasizing recent developments with compounds acting on trans-membrane proteins involved in drug efflux or uptake.

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Interaction of multidrug-resistant Chinese hamster ovary cells with amphiphiles

Cited by 45 publications

References 40 publications

Chloroquine Resistance Reversal Agents as Promising Antimalarial Drugs

Chloroquine Resistance Reversal Agents as Promising Antimalarial Drugs

The ATPase and ATP‐binding functions of P‐glycoprotein

Chemosensitizers in Drug Transport Mechanisms Involved in Protozoan Resistance

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