Internal duplication and homology with bacterial transport proteins in the mdr1 (P-glycoprotein) gene from multidrug-resistant human cells

Chen, Chang jie; Chin, Janice E.; Ueda, Kazumitsu; Clark, Douglas P.; Pastan, Ira; Gottesman, Michael M.; Roninson, Igor B.

doi:10.1016/0092-8674(86)90595-7

Cited by 1,821 publications

(909 citation statements)

References 36 publications

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“…Significant (Po0.05) and highly significant (Po0.01) values were marked with single and double asterisks, respectively study provides new insights into a general mechanism regulating the activity of ABC transporters ( Figure 6). Since multiple drug resistance of tumour cells is known to rely on the functional activity of ABC transporters, 35,36 our results point towards new strategies which may contribute to the success of antineoplastic combined strategies.…”

Section: Discussionmentioning

confidence: 91%

UV irradiation inhibits ABC transporters via generation of ADP-ribose by concerted action of poly(ADP-ribose) polymerase-1 and glycohydrolase

et al. 2003

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ATP-binding cassette (ABC) transporters are involved in the transport of multiple substrates across cellular membranes, including metabolites, proteins, and drugs. Employing a functional fluorochrome export assay, we found that UVB irradiation strongly inhibits the activity of ABC transporters. Specific inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1) restored the function of ABC transporters in UVB-irradiated cells, and PARP-1-deficient cells did not undergo UVBinduced membrane transport inhibition. These data suggest that PARP-1 activation is necessary for ABC transporter functional downregulation. The hydrolysis of poly(ADPribose) by poly(ADP-ribose) glycohydrolase (PARG) was also required, since specific PARG inhibitors, which limit the production of ADP-ribose molecules, restored the function of ABC transporters. Furthermore, ADP-ribose molecules potently inhibited the activity of the ABC transporter Pglycoprotein. Hence, poly(ADP-ribose) metabolism appears to play a novel role in the regulation of ABC transporters.

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Section: Discussionmentioning

confidence: 91%

UV irradiation inhibits ABC transporters via generation of ADP-ribose by concerted action of poly(ADP-ribose) polymerase-1 and glycohydrolase

et al. 2003

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“…P-gp, a well-known efflux pump responsible for multiple drug resistance, plays a major role in the cells to transport genistein from the intra-cell to the outside [23,24]. As represented in Figure 4(c), the small intestinal P-gp level in mice treated with stachyose alone showed a significant decrease ( p <0.05), but an independent treatment with genistein showed a significant increase ( p <0.05), relative to the intestinal P-gp expression in the untreated control group.…”

Section: Resultsmentioning

confidence: 99%

Non-digestible stachyose promotes bioavailability of genistein through inhibiting intestinal degradation and first-pass metabolism of genistein in mice

Lin

et al. 2017

Food & Nutrition Research

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This study was designed to explore the molecular mechanism of stachyose in enhancing the gastrointestinal stability and absorption of soybean genistein in mice. Male Kunming mice in each group (n = 8) were administered by intragastric gavage with saline, stachyose (250 mg/kg·bw), genistein (100 mg/kg·bw), and stachyose (50, 250, and 500 mg/kg·bw) together with genistein (100 mg/kg·bw) for 4 consecutive weeks, respectively, and then their urine, feces, blood, gut, and liver were collected. UPLC-qTOF/MS analysis showed that levels of genistein and its metabolites (dihydrogenistein, genistein 7-sulfate sodium salt, genistein 4’-β-D-glucuronide, and genistein 7-β-D-glucuronide) in serum and urine were increased with an increase in stachyose dosages in mice. Furthermore, the feces level of genistein aglycone was also elevated by co-treatment of stachyose with genistein. However, the feces concentration of dihydrogenistein, a characteristic metabolite of genistein by gut microorganism, was decreased by stachyose administration in a dose-dependent manner. Additionally, the simultaneous administration with stachyose and genistein in mice could decrease intestinal SULT, UGT, P-gp, and MRP1 expression, relative to the treatment with individual stachyose or genistein. These results demonstrate that stachyose-mediated inhibition against the intestinal degradation of genistein and expression of phase II enzymes and efflux transporters can largely contribute to the elevated bioavailability of soybean genistein.

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“…The identities (indicated by exclamation marks above the alignment) and the consensus sequence (provided below the alignment) illustrate the high degree of sequence similarity exhibited by these proteins. Table 2 presents binary comparison scores for the proteins included in Figure 3 as well as for an ATP binding domain of a human (Hs) multidrug resistance protein (Mdr3) (Chen et al, 1986). All of these proteins exhibit comparison scores in excess of 10 SD and are therefore homologous, but the Mdr3(Hs) protein is more distant from the ATP binding constituents of the ABC-2 subfamily than they are from each other.…”

Section: Resultsmentioning

confidence: 99%

A new subfamily of bacterial ABC‐type transport systems catalyzing export of drugs and carbohydrates

1992

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Sequence comparison studies revealed that the drug resistance transporter of Streptomycespeucetius (DrrAB) and two nodulation gene products (NodIJ) of Rhizobium leguminosarurn are homologous to proteins encoded by three sets of genes that comprise capsular polysaccharide export systems in gram-negative bacteria: KpsTM of Escherichia coli, BexABC of Haemophilus influenzae, and CtrDCB of Neisseria meningitidis. These five systems comprise a new subfamily within the family of ATP binding cassette (ABC)-type transporters. We have termed this subfamily the ABC-2 subfamily. For three of the systems comprising this subfamily (Drr, Nod, and Kps) only one integral membrane constituent has been identified, whereas for the other two systems (Bex and Ctr) two dissimilar integral membrane constituents have been found. This observation suggests that the transmembrane channels of ABC-2-type transporters can be formed of homo-or heterooligomers as is true of several other classes of transport systems.

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Internal duplication and homology with bacterial transport proteins in the mdr1 (P-glycoprotein) gene from multidrug-resistant human cells

Cited by 1,821 publications

References 36 publications

UV irradiation inhibits ABC transporters via generation of ADP-ribose by concerted action of poly(ADP-ribose) polymerase-1 and glycohydrolase

UV irradiation inhibits ABC transporters via generation of ADP-ribose by concerted action of poly(ADP-ribose) polymerase-1 and glycohydrolase

Non-digestible stachyose promotes bioavailability of genistein through inhibiting intestinal degradation and first-pass metabolism of genistein in mice

A new subfamily of bacterial ABC‐type transport systems catalyzing export of drugs and carbohydrates

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