Abstract：
:P-glycoprotein (P-gp) is the most well-known ATP-binding cassette (ABC) transporter involved in unidirectional substrate translocation across the membrane lipid bilayer, thereby causing the typical multidrug resistance (MDR) phenotype expressed in many cancers. We observed that in human CEM acute lymphoblastic leukemia cells expressing various degrees of chemoresistance and where P-gp was the sole MDR-related ABC transporter detected, the amount of esterified cholesterol increased linearly with the level of resistance to vinblastine while the amounts of total and free cholesterol increased in a nonlinear way. Membrane cholesterol controlled the ATPase activity of P-gp in a linear manner, whereas the P-gp-induced daunomycin efflux decreased nonlinearly with the depletion of membrane cholesterol. All these elements suggest that cholesterol controls both the ATPase and the drug efflux activities of P-gp. In addition, in CEM cell lines that expressed increasing levels of elevated chemoresistance, the amount of P-gp increases to a plateau value of 40% of the total membrane proteins and remained unvaried while the amount of membrane cholesterol increased with the elevation of the MDR level, strongly suggesting that cholesterol may be directly involved in the typical MDR phenotype. Finally, we showed that the decreased daunomycin efflux by P-gp due to the partial depletion of membrane cholesterol was responsible for the efficient chemosensitization of resistant CEM cells, which could be totally reversed after cholesterol repletion.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Gayet L,Dayan G,Barakat S,Labialle S,Michaud M,Cogne S,Mazane A,Coleman AW,Rigal D,Baggetto LGdoi
10.1021/bi048669wsubject
Has Abstractpub_date
2005-03-22 00:00:00pages
4499-509issue
11eissn
0006-2960issn
1520-4995journal_volume
44pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract：:Site-directed mutagenesis, electron microscopy, and X-ray crystallography were used to probe the structural basis of annexin IV-induced membrane aggregation and the inhibition of this property by protein kinase C phosphorylation. Site-directed mutants that either mimic (Thr6Asp, T6D) or prevent (Thr6Ala, T6A) phosphor...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi002507s
更新日期：2001-04-03 00:00:00
abstract：:To understand the relationship between the chemical structure of polar molecules and their membrane location, the behavior of dansyl (dimethylaminonaphthalenesulfonyl) and related polar fluorescent probes was examined. The depth of these probes in lipid bilayers was determined by parallax analysis of fluorescence quen...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi9726234
更新日期：1998-03-31 00:00:00
abstract：:A type II topoisomerase is essential for decatenating DNA replication products, and it accomplishes this task by passing one DNA duplex through a transient break in a second duplex. The B' domain of topoisomerase II contains three highly conserved motifs, EGDSA, PL(R/K)GK(I/L/M)LNVR, and IMTD(Q/A)DXD. We have investig...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi991328b
更新日期：2000-02-15 00:00:00
abstract：:Haemadin is a 57-amino acid thrombin inhibitor from the land-living leech Haemadipsa sylvestris, whose structure has recently been determined in complex with human alpha-thrombin. Here we communicate the effect of ionic strength on the kinetics of the inhibition of human alpha-thrombin by haemadin, by using thrombin m...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi011605q
更新日期：2002-02-26 00:00:00
abstract：:Enzyme IIA(Glc) (EIIA(Glc)) of the phosphoenolpyruvate phosphotransferase system for the uptake of glucose in Escherichia coli and Salmonella inhibits the maltose ATP-binding cassette transporter (MalE-FGK2) by interaction with the nucleotide-binding and -hydrolyzing subunit MalK, a process termed inducer exclusion. W...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/acs.biochem.6b00721
更新日期：2016-09-27 00:00:00
abstract：:The actinomycin biosynthetic gene cluster of Streptomyces chrysomallus harbors two paralogous genes, acmI and acmL, encoding methyltransferases. To unveil their suspected role in the formation of 3-hydroxy-4-methyl-anthranilic acid (4-MHA), the building block of the actinomycin chromophore, each gene was expressed in ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi101422r
更新日期：2010-11-16 00:00:00
abstract：:The crystal structure of a cytochrome P450 from the thermoacidophile Picrophilus torridus, CYP231A2 (PTO1399), has been solved. This structure reveals a wide open substrate access channel. To better understand ligand-induced structural transitions in CYP231A2, protein-ligand interactions were investigated using 4-phen...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi702240k
更新日期：2008-02-19 00:00:00
abstract：:We have used a fluorescent analogue of ATP, mantATP [2'(3')-O-(N-methylanthraniloyl)-adenosine 5'-triphosphate; Hiratsuka T. (1983) Biochim. Biophys. Acta 742, 496-508], and made a detailed kinetic study of the interaction of mantATP and mantADP with S1 and acto-S1. We have shown that these analogues behave like ATP a...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00216a017
更新日期：1991-01-15 00:00:00
abstract：:The cDNA that encodes the proenzyme form of human fibroblast collagenase has been expressed in Escherichia coli. It has been shown by a number of criteria to be functionally identical with the enzyme isolated from human sources. Mutations of each of three cysteine residues found in procollagenase were constructed by s...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00217a008
更新日期：1991-01-22 00:00:00
abstract：:The 70-kDa heat-shock protein (Hsp70) has been cloned and sequenced from bovine cardiac muscle. On the basis of sequence features, the gene corresponds to the cytoplasmic form of Hsp70. This cardiac Hsp70 cDNA clone has an open reading frame of 1926 bp coding for 641 amino acids and a predicted molecular mass of 70.25...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi049036k
更新日期：2004-10-26 00:00:00
abstract：:Integrin conformational changes mediate integrin activation and signaling triggered by intracellular molecules or extracellular ligands. Even though it is known that αβ transmembrane domain separation is required for integrin signaling, it is still not clear how this signal is transmitted from the transmembrane domain...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi101462h
更新日期：2010-11-30 00:00:00
abstract：:K(+) channels are revered for their universal action of suppressing electrical activity in nerve and muscle, as well as regulating salt and water transport in epithelial tissues involved in metabolism and digestion. These multisubunit membrane-embedded proteins carry out their physiological chore, selectively allowing...
journal_title：Biochemistry
pub_type： 杂志文章,评审
doi：10.1021/bi8018515
更新日期：2009-01-27 00:00:00
abstract：:Complete resonance assignments of nonexchangeable base protons and sugar protons in d-GGTACGCGTACC at 500 MHz have been obtained by two-dimensional correlated spectroscopy (COSY) and nuclear Overhauser enhancement spectroscopy (NOESY). The characteristic phase-sensitive multiplet patterns of the ntrasugar cross peaks ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00410a050
更新日期：1988-05-17 00:00:00
abstract：:A series of secreted proteases are included among the virulence factors documented for Staphylococcus aureus. In light of increasing antibiotic resistance of this dangerous human pathogen, these proteases are considered as suitable targets for the development of novel therapeutic strategies. The recent discovery of st...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi035310j
更新日期：2003-11-25 00:00:00
abstract：:The three-dimensional high-resolution structure of rhodopsin is unknown, as is the case for almost all integral membrane patients. As part of an alternative approach to determine of membrane protein structure, we are pursuing the structure of cytoplasmic domains of this G-protein receptor. A peptide, rhoIII, with the ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00045a002
更新日期：1995-11-14 00:00:00
abstract：:We have measured the base-pair lifetimes in oligodeoxynucleotides containing tracts of A.T base pairs using imino proton magnetic resonance. When the tract contains more than four consecutive A.T base pairs, possibly including a 5'-AT step but not a 5'-TA step, anomalously long lifetimes are observed. For example, the...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00425a004
更新日期：1988-12-13 00:00:00
abstract：:In circulation the phospholipid transfer protein (PLTP) facilitates the transfer of phospholipid-rich surface components from postlipolytic chylomicrons and very low density lipoproteins (VLDL) to HDL and thereby regulates plasma HDL levels. To study the molecular mechanisms involved in PLTP-mediated lipid transfer, w...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi0621866
更新日期：2007-02-06 00:00:00
abstract：:Eukaryotic initiation factor 5 (eIF5) plays multiple roles in translation initiation. Its N-terminal domain functions as a GTPase-activator protein (GAP) for GTP bound to eIF2, while its C-terminal region nucleates the interactions between multiple translation factors, including eIF1, which acts to inhibit GTP hydroly...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi052387u
更新日期：2006-04-11 00:00:00
abstract：:Intracellular retinoid-binding proteins are small, tightly folded, compact proteins, which appear to be involved in the delivery of retinoids to microsomal metabolic enzymes, among other potential roles. Recently, it has been demonstrated that two of these binding proteins, cellular retinol-binding protein (CRBP) and ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00176a017
更新日期：1994-03-15 00:00:00
abstract：:Myeloperoxidase plays a fundamental role in oxidant production by neutrophils. The enzyme uses hydrogen peroxide to oxidize chloride (Cl-), bromide (Br-), iodide (I-), and the pseudohalide thiocyanate (SCN-) to their respective hypohalous acids. This study for the first time presents transient kinetic measurements of ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi9818772
更新日期：1998-12-22 00:00:00
abstract：:The complexity of rat liver poly (A)+ messenger RNA (mRNA) has been measured by analysis of the kinetics of hydridization with both complementary DNA (cDNA) and single copy DNA. The complementary DNA-poly(A)+ mRNA hybridization reaction demonstrates the existence of three abundance classes representing 18, 37, and 45%...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00596a014
更新日期：1978-02-07 00:00:00
abstract：:Kinetic and spectroscopic studies have shown that the conserved active site residue His200 of the extradiol ring-cleaving homoprotocatechuate 2,3-dioxygenase (FeHPCD) from Brevibacterium fuscum is critical for efficient catalysis. The roles played by this residue are probed here by analysis of the steady-state kinetic...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/acs.biochem.5b00709
更新日期：2015-09-01 00:00:00
abstract：:The vitamin D receptor (VDR) binds 1,25-dihydroxyvitamin D(3) and mediates its actions on gene transcription by heterodimerizing with retinoid X receptors (RXRs) on direct repeat (DR+3) vitamin D responsive elements (VDREs) located in target genes. The VDRE binding function of VDR has been primarily ascribed to the zi...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi9916574
更新日期：1999-12-07 00:00:00
abstract：:The photochemical and subsequent thermal reactions of the mouse short-wavelength visual pigment (MUV) were studied by using cryogenic UV-visible and FTIR difference spectroscopy. Upon illumination at 75 K, MUV forms a batho intermediate (lambda(max) approximately 380 nm). The batho intermediate thermally decays to the...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi025883g
更新日期：2002-08-06 00:00:00
abstract：:The thermotropic behavior of purified human complement protein C9 was investigated by high-sensitivity differential scanning calorimetry. When dissolved in physiological buffers (pH 7.2, 150 mM NaCl), C9 underwent three endothermic transitions with transition temperatures (Tm) centered at about 32, 48, and 53 degrees ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00240a035
更新日期：1991-07-02 00:00:00
abstract：:Traditionally, assigning the heme protein resonances has relied heavily on the comparison of spectra arising from protein reconstituted with specifically deuterated hemes and the native form. Such an approach can identify tentatively the broad, overlapping signals in the Fe(II) high-spin heme protein spectra. Although...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00202a012
更新日期：1994-09-13 00:00:00
abstract：:The enzyme hydrogenase, from the photosynthetic bacterium Chromatium, was purified to homogeneity after solubilization of the particulate enzyme with deoxycholate. The purification procedure included ammonium sulfate fractionation, treatment with manganous phosphate gel, heating at 63 degrees, DEAE-cellulose chromatog...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00683a001
更新日期：1975-06-17 00:00:00
abstract：:ADP-glucose pyrophosphorylase (ADPGlc PPase) catalyzes the conversion of glucose 1-phosphate and ATP to ADP-glucose and pyrophosphate. As a key step in glucan synthesis, the ADPGlc PPases are highly regulated by allosteric activators and inhibitors in accord with the carbon metabolism pathways of the organism. Crystal...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi701933q
更新日期：2008-04-15 00:00:00
abstract：:Chicken nucleoside triphosphate diphosphohydrolase 8 (NTPDase8) is a cell surface ectonucleotidase with a large extracellular domain (ECD) containing the active site and is anchored to the membrane by two transmembrane domains (TMDs) at the N- and C-termini. Unlike other cell surface NTPDases that have been characteri...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi901820c
更新日期：2010-01-12 00:00:00
abstract：:The carbon monoxide binding curve to human hemoglobin A0 has been measured to high precision in experimental conditions of 600 microM heme, 0.1 M N-(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid, 0.1 M NaCl, 10 mM inositol hexaphosphate, 1 mM disodium ethylenediaminetetraacetic acid, pH 6.94, and 25 degrees C. Co...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00394a031
更新日期：1987-10-06 00:00:00
