ライフサイエンスコーパス: MRP1

1 MRP1 also confers resistance to arsenic in association w

2 MRP1 and MRP5 are also detected in multidrug resistant C

3 MRP1 expression markedly increased upon macrophage activ

4 MRP1 inhibition prevented the decline in intracellular G

5 MRP1 mediated efficient ATP-dependent transport of LNO(2

6 MRP1 was expressed in 8 (50%) of 16 tumors, and MRP2 was

7 MRP1 was not decreased in amount in single-step variants

8 MRP1, 2, 3 and 7 gene expression was highest in HepG2 ce

9 MRP1-dependent transport of leukotriene C(4) and estradi

10 1/ATP-binding cassette subfamily C member 1 (MRP1/ABCC1) and the PI3/AKT pathway.

11 Multidrug resistance protein 1 (MRP1) actively transports a wide variety of drugs out of

12 chopulmonary multidrug resistance protein 1 (MRP1) and permeability glycoprotein (P-gp) and assess th

13 The multidrug resistance protein 1 (MRP1) encoded by ABCC1 was originally discovered as a ca

14 1 (MDR1) and multidrug resistance protein 1 (MRP1) gene products is a major cause of multidrug resist

15 e multidrug resistance-associated protein 1 (MRP1) has been closely linked to poor treatment response

16 Multidrug resistance-associated protein 1 (MRP1) is a drug efflux transporter that has been implica

17 t multidrug resistance-associated protein 1 (MRP1) is prevalent in many cancer types, the functional

18 n multidrug resistance-associated protein 1 (MRP1) was mutated to either a different aromatic residue

19 , multidrug resistance-associated protein 1 (MRP1), and breast cancer resistance protein (BCRP), whic

20 ilencing the multidrug resistance protein 1 (MRP1), before chemotherapeutic drug delivery in vivo wit

21 f multidrug resistance-associated protein 1 (MRP1), is regulated by yeast casein kinase 2alpha (Cka1p

22 , multidrug resistance-associated protein 1 (MRP1), mediates this release potentially as a dinitrosyl

23 ting multidrug resistance-related protein 1 (MRP1).

24 ship between multidrug resistance protein 1 (MRP1, ABCC1) expression and cellular sensitivity to mito

25 , ABCB1) and multidrug resistance protein 1 (MRP1, ABCC1) to confirm the selectivity toward BCRP.

26 , multidrug resistance-associated protein 1 (MRP1, ABCC1), and breast cancer resistance protein (BCRP

27 d multidrug resistance-associated protein 1 (MRP1, ABCC1).

28 pic 5-domain multidrug resistance protein 1 (MRP1/ABCC1) extrudes a variety of drugs and organic anio

29 transporter multidrug resistance protein 1 (MRP1/ABCC1) is responsible for the cellular export of a

30 transporter, multidrug resistance protein 1 (MRP1/ABCC1), confers resistance to a broad range of anti

31 (ABCB1/Pgp), multidrug resistance protein 1 (MRP1/ABCC1), or multidrug resistance protein 2 (MRP2/ABC

32 transporter multidrug resistance protein 1 (MRP1/ABCC1).

33 ), multidrug-resistant-associated protein 1 (MRP1; ABCC1), MRP2 (ABCC2), and MRP4 (ABCC4).

34 e multidrug resistance-associated protein-1 (MRP1) and the reduction of substrate export by this tran

35 express the multidrug resistance protein-1 (MRP1) and use this as their major exporter of GSSG.

36 r extents of multidrug resistance protein-1 (MRP1) expression, and greater MRP1-mediated efflux of NO

37 substrate of multidrug resistance protein-1 (MRP1), into HEK-MRP1 cells, which overexpress MRP1, and

38 nzymes including GSTA2, GSTP1, CYP3A4, HO-1, MRP1, and MRP5.

39 ic parameters of As(GS)3 for HEK-Asn19/23Gln-MRP1 were similar to those of HeLa/HEK-SF-MRP1 and HeLa-

40 e-negative breast cancer model following 80% MRP1 silencing compared with the continuous tumor growth

41 C transporters such as P-glycoprotein/ABCB1, MRP1/ABCC1, and MXR/ABCG2 seems to be a major cause of f

42 teins ABCB1 (P-gp), ABCG2 (BCRP), and ABCC1 (MRP1), which are involved in the formation of multidrug

43 s inhibited by MK571, an inhibitor of ABCC1 (MRP1), but not by inhibitors of ABCB1 (MDR-1, P-glycopro

44 ) expression and the drug-transporter ABCC1 (MRP1) were linked to thiopurine sensitivity, suggesting

45 idrug resistance-associated protein 1 (ABCC1/MRP1; herein referred to as ABCC1), we measured N1(IC) a

46 such as ABCB1/P-glycoprotein/MDR1 and ABCC1/MRP1 causes multidrug resistance in cancer chemotherapy.

47 r therapeutic development to sensitize ABCC1/MRP1-mediated drug resistance in cancer chemotherapy.

48 These findings suggest that ABCC1/MRP1 may exist and function as a dimer and that MSD0L0 l

49 the human full-length ABC transporter ABCC1/MRP1 using several biochemical approaches.

50 y the ATP-binding cassette transporter ABCC1/MRP1, and is then able to initialize cascades downstream

51 nction when coexpressed with wild-type ABCC1/MRP1.

52 In addition, MRP1 regulates redox homeostasis, inflammation, and horm

53 enic, a human carcinogen, is a high-affinity MRP1 substrate as arsenic triglutathione [As(GS)3].

54 y in the 4-position were more active against MRP1 than derivatives with amide functionality.

55 Moreover, mutation of Thr249 to alanine (MRP1-T249A) also resulted in decreased MRP1-dependent tr

56 ne D4, a known MRP1 substrate, or VX-710, an MRP1 modulator, restored flutamide and hydroxyflutamide

57 es of Trypanosoma brucei apoMRP1/MRP2 and an MRP1/MRP2-gRNA complex.

58 Membrane vesicles from an MRP1-transfected HeLa cell line lacking membrane-associa

59 lation of the cytotoxic drug vincristine, an MRP1 substrate, depleted virus from naturally latent CD1

60 tance of the combined effect of GST P1-1 and MRP1 in protecting cells from the cytotoxic effects of N

61 tand the role of glutathione, GSTP1a-1a, and MRP1 in NQO detoxification, we have characterized the ki

62 efflux pump P-glycoprotein (P-gp, ABCB1) and MRP1 (ABCC1).

63 ated drug-resistant cells (i.e. NCI/ADR) and MRP1-mediated resistant cells (i.e. MCF-7/VP).

64 l cell lines (e.g., wild-type HeLa cells and MRP1-overexpressing HeLa-R cells).

65 Indeed, CK2alpha and MRP1 interact physically, and recombinant CK2 phosphoryl

66 rubicin accumulation in MRP1 CK2alpha(-) and MRP1-T249A cells compared with MRP1 cells.

67 lts suggest that glutathione conjugation and MRP1-mediated conjugate transport can attenuate LNO(2) b

68 gate the role of glutathione conjugation and MRP1-mediated efflux in the regulation of PPARgamma-depe

69 rly affected by nonenzymatic conjugation and MRP1-mediated efflux.

70 While nonenzymatic QO-SG formation and MRP1-mediated conjugate efflux result in low-level prote

71 selective for ABCG2 over P-glycoprotein and MRP1, appeared not to be transported by ABCG2, and was a

72 [alpha-32P]8-azidoATP to P-glycoprotein and MRP1, with inhibition curves comparable with those of N-

73 ased modulators targeting P-glycoprotein and MRP1.

74 ed sensitivity toward daunorubicin (P-gp and MRP1) and SN-38 (BCRP) in A2780/ADR (P-gp), H69AR (MRP1)

75 -sestamibi is a known substrate for P-gp and MRP1, which are established cellular drug efflux transpo

76 involved in drug resistance, namely GST and MRP1 (multidrug resistance-associated protein 1), are cr

77 Considering this, and because GSTP1 and MRP1 are up-regulated during macrophage activation, this

78 iability studies demonstrated that GSTP1 and MRP1 protect activated macrophages from NO cytotoxicity.

79 Considering this and that GSTs and MRP1 form an integrated detoxification unit with chemoth

80 that glutathione conjugation of NO(2)-LA and MRP1-mediated efflux of the conjugates were associated w

81 n-transporting polypeptide) mRNA levels, and MRP1 protein levels; however, differences existed in MRP

82 ral other transporters (e.g. OAT2, OAT3, and MRP1) have also been proposed as important PAH transport

83 notypes of SNPs in the ALOX5 (rs2115819) and MRP1 (rs119774) genes and changes in FEV(1) (p < 0.05),

84 rimidines using the doxorubicin selected and MRP1 overexpressing small cell lung cancer cell line H69

85 ficant differences between the wild-type and MRP1-overexpressing cells in efflux and accumulation of

86 ibited by several conjugated organic anions (MRP1 substrates) as well as the metalloid antimonite (K(

87 ensitive space and was inhibited by the anti-MRP1 antibody QCRL3.

88 or P-glycoprotein) and ABCC1 (also known as MRP1) whose inhibition remains a priority to circumvent

89 wn as MDR1 or P-gp) and ABCC1 (also known as MRP1), whose inhibition remains a priority to circumvent

90 lpha results in decreased phosphorylation at MRP1-Thr249.

91 S)3 transport kinetics were observed between MRP1-enriched membrane vesicles prepared from human embr

92 , these data suggest that cross-talk between MRP1 glycosylation and phosphorylation occurs and that p

93 ATP analogs bind MRP1 with reduced apparent affinity, inducing a partiall

94 etermined the molecular structures of bovine MRP1 in two conformations: an apo form at 3.5 A without

95 t of dihydrotestosterone was not affected by MRP1.

96 prevented by the MRP1 inhibitor MK571 and by MRP1 small interfering RNA.

97 reducing their transport out of the cell by MRP1.

98 nt with the interpretation that MX efflux by MRP1 involves cotransport of MX and glutathione.

99 ss MRP1, and monitored the calcein efflux by MRP1.

100 ivated metabolite of PABA/NO was effluxed by MRP1 in a GSH-dependent manner.

101 key physiological organic anions effluxed by MRP1, and an ever growing body of evidence indicates tha

102 GSSG export by MRP1 leads to a perturbation of endothelial redox state

103 by MDR1 Pgp and, to a much lesser extent, by MRP1, but not MRP2-MRP6 or BCRP/MXR.

104 mon currency for NO transport and storage by MRP1 and GST P1-1, respectively.

105 As(GS)(3) transport by MRP1 was osmotically sensitive and was inhibited by seve

106 t not dihydrotestosterone are transported by MRP1 and that these findings may contribute to our under

107 NQO was not transported by MRP1 either alone or in the presence of S-methyl glutath

108 confirmed that thiodione was transported by MRP1, and that glutathione is an essential substrate for

109 In Jurkat cells, MRP1 was largely localized to the plasma membrane, and t

110 in MRP1 cells, but not in MRP1 CK2alpha(-), MRP1-T249A, or MRP1-T249E cells, suggesting that CK2alph

111 lts demonstrate the utility of the two-color MRP1 construct for investigating ATP-binding cassette tr

112 Two-color MRP1 transport activity was normal, as shown by vesicula

113 uctural dynamics, we engineered a "two-color MRP1" construct by fusing green fluorescent protein (GFP

114 In conclusion, MRP1 transports inorganic arsenic as a tri-GSH conjugate

115 n the brain and hence form the corresponding MRP1 substrate tracers in situ.

116 protein Ycf1p and its mammalian counterpart, MRP1, belong to the ABCC subfamily of ATP-binding casset

117 a noncompetitive inhibitor of daunorubicin (MRP1), calcein AM (P-gp), and pheophorbide A (BCRP) tran

118 nine (MRP1-T249A) also resulted in decreased MRP1-dependent transport, whereas a phosphomimicking mut

119 er cell lines where CK2 inhibition decreased MRP1-mediated efflux of doxorubicin and increased doxoru

120 d 2-related factor 2 (Nrf2), which decreased MRP1 and GSTP1 expression, concomitant with reduced (59)

121 across the cell membrane via the ATP-driven MRP1 pump.

122 erly decorated for the preparation of either MRP1 or P-gp highly selective inhibitors.

123 Endothelial MRP1 may provide a novel therapeutic target for preventi

124 ed by increased drug resistance and enhanced MRP1-mediated drug efflux.

125 favor a mechanism for glutathione-enhanced, MRP1-mediated QO-SG transport that does not involve cotr

126 n parental control cells that do not express MRP1.

127 of CK2alpha in MCF7-derived cells expressing MRP1 [MRP1 CK2alpha(-)] resulted in increased doxorubici

128 The apparent K(m) of As(GS)(3) for MRP1 was 0.32 microM, suggesting a remarkably high relat

129 lkyl side chains proved to be beneficial for MRP1 inhibition.

130 lation in macrophages, indicating a role for MRP1 in transporting DNICs out of cells.

131 at glutathione is an essential substrate for MRP1-mediated transport.

132 Furthermore, luciferase activity from MRP1 promoter/luciferase gene reporter constructs was si

133 eta-d-glucuronide into vesicles derived from MRP1 CK2alpha(-) cells was decreased compared with MRP1

134 microM and a V(max) comparable to other good MRP1 substrates.

135 nce protein-1 (MRP1) expression, and greater MRP1-mediated efflux of NO2-OA-glutathione conjugates.

136 and SN-38 (BCRP) in A2780/ADR (P-gp), H69AR (MRP1), and MDCK II BCRP (BCRP) cells.

137 tidrug resistance protein-1 (MRP1), into HEK-MRP1 cells, which overexpress MRP1, and monitored the ca

138 The addition of exogenous GSTP1-1 to HeLa-MRP1 vesicles resulted in GSH-dependent As(III) transpor

139 Structural analysis of human MRP1-NBD1 revealed that the Walker A S685 forms a hydrog

140 ions were examined for their effect on human MRP1-mediated uptake of tritiated estradiol glucuronide

141 d was not observed in aortas of hypertensive MRP1-/- mice.

142 To test this idea, MRP1-Phe594 mutants were expressed in human embryonic ki

143 ted in increased doxorubicin accumulation in MRP1 cells, but not in MRP1 CK2alpha(-), MRP1-T249A, or

144 ed intracellular doxorubicin accumulation in MRP1 CK2alpha(-) and MRP1-T249A cells compared with MRP1

145 inhibitor that increased MX accumulation in MRP1-expressing MCF7 cells but had no effect on MRP-poor

146 on caused by hypertension was ameliorated in MRP1-/- mice.

147 tein levels; however, differences existed in MRP1 localization and function.

148 ion (MRP1-T249E) led to dramatic increase in MRP1-dependent transport.

149 bicin accumulation in MRP1 cells, but not in MRP1 CK2alpha(-), MRP1-T249A, or MRP1-T249E cells, sugge

150 tiopronin led to a significant reduction in MRP1 protein.

151 ction in human NB cells results in increased MRP1 mRNA and protein levels, which in turn is accompani

152 ecular nanoswitch triggered by the increased MRP1 expression within the tumor tissue microenvironment

153 vered ASOs and DOX to cell nuclei, inhibited MRP1 and BCL2 protein synthesis, and substantially incre

154 the presence of glutathione, but uptake into MRP1-containing vesicles was entirely attributable to it

155 In contrast, Taxotere selectively killed MRP1-expressing leukemia cells, which did not undergo G2

156 ating the cells with leukotriene D4, a known MRP1 substrate, or VX-710, an MRP1 modulator, restored f

157 In contrast, Raji cells had little MRP1 at the plasma membrane and did not export calcein u

158 wenty-eight SNPs in the ALOX5, LTA4H, LTC4S, MRP1, and cysLT1R genes, and an ALOX5 repeat polymorphis

159 the stably transduced MCF7 derivative, MCF7/MRP1-10, resulted in strong inhibition of LNO(2)-induced

160 xpression of drug transporter proteins MDR1, MRP1, and ABCG2.

161 alpha in MCF7-derived cells expressing MRP1 [MRP1 CK2alpha(-)] resulted in increased doxorubicin sens

162 Mutant MRP1 lacking N-linked glycosylation [Asn19/23/1006Gln; s

163 nsport, whereas a phosphomimicking mutation (MRP1-T249E) led to dramatic increase in MRP1-dependent t

164 Reversan represents a new class of nontoxic MRP1 inhibitor, which may be clinically useful for the t

165 mmunohistochemical assessment (grade 0-3) of MRP1 and P-gp expression in the lung by using parametric

166 storage function of GST P1-1 and ability of MRP1 to efflux DNICs are vital in protection against NO

167 tional studies showed that in the absence of MRP1, PABA/NO activated the extracellular-regulated and

168 ally determine intracellular accumulation of MRP1 substrates using a p53-responsive reporter as an in

169 Expression and functional activity of MRP1 were determined using flow cytometry and SECM, and

170 required for proper folding and assembly of MRP1 into a fully transport competent native structure.

171 e tracer can allow noninvasive assessment of MRP1 activity in vivo.

172 Structural comparison of MRP1 and P-glycoprotein advances our understanding of th

173 complex role of CL5 for stable expression of MRP1 at the plasma membrane and more specifically show t

174 o TM10 are critical for stable expression of MRP1 at the plasma membrane.

175 However, expression of MRP1 in the stably transduced MCF7 derivative, MCF7/MRP1

176 he most effective at restoring expression of MRP1 mutants K513A, K516A, E521A, and E535A.

177 nt to Adriamycin due to either expression of MRP1 or lack of G2 checkpoints.

178 mational change in the COOH-proximal half of MRP1.

179 However, the identification of MRP1, another member of the ABC drug transporter family,

180 grees, without any significant inhibition of MRP1.

181 are responsible for altering the kinetics of MRP1-mediated As(GS)3 transport.

182 Pulse-chase labeling of MRP1 with (35)S-methionine and (35)S-cysteine and pulse-

183 aster in patients (n = 6) with low levels of MRP1 expression (grade 0-1) and mean T1/2 of 105 minutes

184 ), compared with those with higher levels of MRP1 expression (grade 2-3, n = 7) and mean T1/2 of 149

185 Latency-associated loss of MRP1 and accumulation of the cytotoxic drug vincristine,

186 The UL138-mediated loss of MRP1 provides a marker for detecting latent HCMV infecti

187 To enable measurement of MRP1 function in the living brain, a series of 6-halopur

188 Herein, we report the measurement of MRP1 functional activity in individual cancer cells usin

189 u(521), and Glu(535) all cause misfolding of MRP1 and target the protein for proteasome-mediated degr

190 bstitution of the aromatic Trp653 in NBD1 of MRP1 with a polar cysteine residue greatly decreases the

191 Overexpression of MRP1 conferred the most significant degree of resistance

192 ed the kinetics and cofactor requirements of MRP1-mediated transport of QO-SG and NQO.

193 xicity can be ascertained; thus, the role of MRP1 in MX resistance remains controversial.

194 upon macrophage activation, and the role of MRP1 in NO-induced (59)Fe release was demonstrated by Mr

195 Specific electrophoretic mobility shifts of MRP1 E-box sequences were detected with nuclear extracts

196 possible substrate binding/transport site of MRP1 at the beginning of a putative substrate translocat

197 sefulness of SECM in quantitative studies of MRP1 inhibitors and suggests that monoclonal antibodies

198 , inhibitors, or transportable substrates of MRP1.

199 Treatment of MRP1-overexpressing cells with tiopronin led to a signif

200 understanding of efflux mechanisms based on MRP1.

201 Differences in their effects on MRP1 and P-gp activity were noted, and a second set of t

202 t cells, disulfiram reverses either MDR1- or MRP1-mediated efflux of fluorescent drug substrates.

203 but not in MRP1 CK2alpha(-), MRP1-T249A, or MRP1-T249E cells, suggesting that CK2alpha regulates MRP

204 for the treatment of neuroblastoma and other MRP1-overexpressing drug-refractory tumors by increasing

205 RP1), into HEK-MRP1 cells, which overexpress MRP1, and monitored the calcein efflux by MRP1.

206 or metabolites, because cells overexpressing MRP1 were less sensitive to the drug and had reduced lev

207 The present study, using paired parental, MRP1-poor, and transduced MRP1-overexpressing MCF7 cells

208 ysically, and recombinant CK2 phosphorylates MRP1-derived peptide in vitro in a Thr249-dependent mann

209 es as a prominent structural class of potent MRP1 inhibitors.

210 hese novel templates gave a number of potent MRP1 modulators with great selectivity against Pgp.

211 Mutation of 19 potential MRP1 phosphorylation sites revealed that HEK-Tyr920Phe/S

212 pports a model in which CK2alpha potentiates MRP1 function via direct phosphorylation of Thr249.

213 In this process, MRP1/MRP2 serves as a matchmaker by binding to guide RNA

214 The multidrug resistance protein MRP1 is an ATP-binding cassette (ABC) transporter that c

215 The multidrug resistance protein MRP1 is an ATP-driven pump that confers resistance to ch

216 the multidrug resistance-associated protein (MRP1) gene is strongly correlated with expression of the

217 Multidrug resistance-associated protein (MRP1) transports solutes in an ATP dependent manner by u

218 the multidrug resistance-associated protein (MRP1, ABCC1) was identified in small cell lung cancer fo

219 sette protein, multidrug resistance protein (MRP1/ABCC1), transports conjugated organic anions (e.g.

220 ce protein, mitoxantrone-resistant protein), MRP1-mediated MX transport is dependent upon the presenc

221 The mitochondrial RNA binding proteins MRP1 and MRP2 form a heteromeric complex that functions

222 we showed that multidrug resistance proteins MRP1 and MRP3 attenuate cytotoxic and transactivating ac

223 p, multidrug resistance-associated proteins (MRP1-MRP6), or the breast cancer resistance protein (BCR

224 To quantify MRP1 structural dynamics, we engineered a "two-color MRP

225 The recombinant MRP1 protein expressed and trafficked normally to the pl

226 9E cells, suggesting that CK2alpha regulates MRP1 function via phosphorylation of Thr249.

227 lpha), the human homolog of Cka1p, regulates MRP1 by phosphorylation at the semiconserved site Thr249

228 The role of CK2 in regulating MRP1 was confirmed in other cancer cell lines where CK2

229 Results MRP1 expression was seen in 12 of 13 patients, while P-g

230 rates in all cells and was unable to reverse MRP1-mediated MDR and had no effect on the parental cell

231 rrolopyrimidine (4) as a novel and selective MRP1 inhibitor.

232 n our continued effort to identify selective MRP1 modulators, we have developed two novel templates,

233 eas individual HEK-Tyr920Phe- and -Ser921Ala-MRP1 mutants were similar to HEK-WT-MRP1.

234 sites revealed that HEK-Tyr920Phe/Ser921Ala-MRP1 transported As(GS)3 like HeLa-WT-MRP1, whereas indi

235 osylation [Asn19/23/1006Gln; sugar-free (SF)-MRP1] expressed in either HEK293 or HeLa cells had low K

236 e of phosphatase inhibitors, both WT- and SF-MRP1-enriched membrane vesicles had a high Km value for

237 ln-MRP1 were similar to those of HeLa/HEK-SF-MRP1 and HeLa-WT-MRP1, whereas those of single glycosyla

238 by forming a single bipartite binding site, MRP1 can recognize a spectrum of substrates with differe

239 clinical trials, the development of specific MRP1 inhibitors is still in its infancy.

240 As such, MRP1 is a multitasking transporter that likely influence

241 nd pulse-chase biotinylation of cell surface MRP1 suggests that membrane protein mislocalization is c

242 sphorylation of Tyr920 and Ser921 can switch MRP1 to a lower-affinity, higher-capacity As(GS)3 transp

243 However, it is now clear that MRP1 serves a broader role than simply mediating the ATP

244 We conclude that MRP1 supports detoxification of NQO via efficient, gluta

245 MCF7 cells, unequivocally demonstrates that MRP1 confers resistance to MX cytotoxicity and that resi

246 c conditions, providing direct evidence that MRP1 is involved in GSH export.

247 lung cancer cell line, H69AR, we found that MRP1 transports arsenite (As(III)) only in the presence

248 These data indicate that MRP1 and MRP3 can modulate the biological effects of 15-

249 th copies of wild-type MRP1, indicating that MRP1 plays a significant role in the drug resistance in

250 using inside-out membrane vesicles show that MRP1 supports ATP-dependent, osmotically sensitive uptak

251 Results show that MRP1 supports efficient transport of QO-SG with a K(m) o

252 The structures show that MRP1/MRP2 is a heterotetramer and, despite little sequen

253 These prior studies also showed that MRP1 and GSTP1 protect tumor cells against NO cytotoxici

254 The results suggest that MRP1-like the alternative MX transporters ABCG2 and ABCB

255 cogene in primary NB tumors, suggesting that MRP1 may be a target for MYCN-mediated gene regulation.

256 lease was demonstrated by Mrp1 siRNA and the MRP1 inhibitor, MK571, which inhibited NO-mediated iron

257 ust export of GSSG that was prevented by the MRP1 inhibitor MK571 and by MRP1 small interfering RNA.

258 Using membrane vesicles prepared from the MRP1-overexpressing lung cancer cell line, H69AR, we fou

259 e expression was less than expression of the MRP1 and 2 genes in HepG2 cells but similar to MRP3 gene

260 Homozygous deletion of the MRP1 gene in primary murine neuroblastoma tumors resulte

261 dy QCRL-4, a selective blocking agent of the MRP1 pumps.

262 similar to or greater than expression of the MRP1, 2 and 3 genes in CWR22Rv1 and TSU-PR1 cells.

263 MRP7 gene compared to the expression of the MRP1, 2 and 3 genes was less variable among the differen

264 Selective inhibition of these MRP1 pumps inside live HeLa cells by MK571 produced a lo

265 This MRP1-associated reduced accumulation of MX was partially

266 Three (MRP1, MRP2, and MRP3) of the four members that have this

267 Thus, MRP1/MRP2 acts as an RNA matchmaker by stabilizing the R

268 tumors resulted in increased sensitivity to MRP1 substrate drugs (vincristine, etoposide, and doxoru

269 reen fluorescent protein (GFP) and TagRFP to MRP1 nucleotide-binding domains NBD1 and NBD2, respectiv

270 ubicin or paclitaxel); (3) siRNA targeted to MRP1 mRNA as a suppressor of pump drug resistance; (4) s

271 ucer, antisense oligonucleotides targeted to MRP1 mRNA as a suppressor of pump resistance and to BCL2

272 ntisense oligonucleotides (ASOs) targeted to MRP1 mRNA as a suppressor of pump resistance, and (d) AS

273 d remarkable affinity and selectivity toward MRP1.

274 g paired parental, MRP1-poor, and transduced MRP1-overexpressing MCF7 cells, unequivocally demonstrat

275 ase and the ATP-binding cassette transporter MRP1.

276 otency against P-gp and another transporter (MRP1), for their apparent permeability (Papp) and for th

277 n cells overexpressing the drug transporters MRP1 or MXR.

278 ysiologically significant ABCC transporters (MRP1, SUR1, and CFTR), determined by using single-partic

279 ox double point mutations, while a truncated MRP1 promoter lacking all three E-boxes exhibited only b

280 e is that the overall Kd value for wild-type MRP1 is mainly determined by ATP binding at NBD1.

281 trate specificities differing from wild-type MRP1 suggested a commonality in the substrate binding po

282 h tumors containing both copies of wild-type MRP1, indicating that MRP1 plays a significant role in t

283 r LTC4 transport activity than the wild-type MRP1, indicating that the hydroxyl group at this positio

284 ities are much higher than that of wild-type MRP1, supporting our hypothesis that the increased relea

285 nts within the promoter, MYCN can upregulate MRP1 expression and modulate drug resistance in NB.

286 As(GS)(3) transport experiments using MRP1 mutants with substrate specificities differing from

287 Furthermore, when MRP1 expression was decreased with RNA interference, GSH

288 cells adapt to the underlying surface, while MRP1 functional activity increases once the dimensions o

289 tly enhanced by coexpression of GSTP1-1 with MRP1.

290 xpressed either alone or in combination with MRP1.

291 2alpha(-) and MRP1-T249A cells compared with MRP1 cells.

292 K2alpha(-) cells was decreased compared with MRP1 vesicles.

293 From comparison with MRP1, a feature distinguishing CFTR from all other ABC t

294 e demonstrating significant correlation with MRP1 expression in the lungs.

295 for As(GS)3, similar to HeLa wild-type (WT) MRP1.

296 n/Tyr920Glu/Ser921Glu were similar to HEK-WT-MRP1, indicating that the phosphorylation-mimicking subs

297 er921Ala-MRP1 mutants were similar to HEK-WT-MRP1.

298 cosylation mutants were like those of HEK-WT-MRP1.

299 921Ala-MRP1 transported As(GS)3 like HeLa-WT-MRP1, whereas individual HEK-Tyr920Phe- and -Ser921Ala-M

300 lar to those of HeLa/HEK-SF-MRP1 and HeLa-WT-MRP1, whereas those of single glycosylation mutants were