Abstract：
:The C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE) modulates the barrier function of claudin-4 via its C-terminal 16 amino acids. In the current study, we investigated the roles of tyrosine residues (Y306, Y310 and Y312) in this region in the modulation of TJs by C-CPE. Single mutations of Y306, Y310 and Y312 to alanine resulted in partial reduction of claudin-4 binding. We also prepared double mutants of C-CPE to further evaluate the roles of these tyrosine residues. Replacement of Y310 and Y312 with alanine (Y310A/Y312A) partly reduced the ability of C-CPE to bind to claudin-4. Double mutants Y306A/Y310A and Y306A/Y312A, however, lost the ability to bind to claudin-4 and to modulate the TJ barrier. We also found that a triple mutant (Y306A/Y310A/Y312A) lost the ability to bind claudin-4, modulate the TJ barrier, and enhance jejunal absorption in rats. These results indicate that tyrosines 306, 310, and 312 are critical for the interaction of C-CPE with claudin-4 and for the modulation of TJ barrier function by C-CPE. This study provides information that should help in the development of claudin modulators based on C-CPE.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Harada M,Kondoh M,Ebihara C,Takahashi A,Komiya E,Fujii M,Mizuguchi H,Tsunoda S,Horiguchi Y,Yagi K,Watanabe Ydoi
10.1016/j.bcp.2006.10.002subject
Has Abstractpub_date
2007-01-15 00:00:00pages
206-14issue
2eissn
0006-2952issn
1873-2968pii
S0006-2952(06)00622-8journal_volume
73pub_type
杂志文章abstract：:The effect of methotrexate (MTX) on 6-mercaptopurine (6-MP) metabolism was studied in four human leukemic cell lines in vitro. CCRF-CEM, WI-L2, TBJ, and HL-60 all expressed thiopurine methyltransferase (TPMT) activity. The cells were grown in horse serum-supplemented RPMI 1640 medium to which was added 4 microM of 6-M...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(97)00681-3
更新日期：1998-05-15 00:00:00
abstract：:This study demonstrates that a long-lasting co-culture of neutrophil surrogates (HL-60 cells), minimally primed by platelet activating factor (PAF), and resting endothelial cells (EC) results in the elaboration of an hyper-adhesive endothelial surface, as measured by the increase in the expression of endothelial adhes...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2010.10.018
更新日期：2011-02-01 00:00:00
abstract：:3'-Azido-2',3'-dideoxy-5-iodouridine (AzIdUrd) and 3'-azido-2',3'-dideoxy-5-bromouridine (AzBdUrd), previously shown to be potent and selective inhibitors of human immunodeficiency virus replication in vitro were minimally toxic to the uninfected human lymphoid cell line H9 (IC50 = 197 and 590 microM, respectively). B...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90396-e
更新日期：1993-01-07 00:00:00
abstract：:Autophagy is generally regarded as a mechanism to promote cell survival. However, autophagy can occasionally be the mechanism responsible of cell demise. We have found that a concomitant depletion of glucose, nutrients and growth factors provoked cell death in a variety of cell lines. This death process was contingent...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2015.09.021
更新日期：2015-12-15 00:00:00
abstract：:For almost 10 years, Nod2 has been known as a cytosolic innate receptor able to sense peptidoglycan from Gram-positive and -negative bacteria and to trigger RIP2- and NF-κB-mediated pro-inflammatory and antibacterial response. Mutations in the gene encoding Nod2 in humans have been associated with Crohn's disease (CD)...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2010.07.016
更新日期：2010-12-15 00:00:00
abstract：:The enzyme S-adenosyl-homocysteine hydrolase (AdoHcyase) which catalyzes the reversible hydrolysis of AdoHcy to adenosine and homocysteine is an adenosine binding protein. In the present study we examined the characteristics of [(3)H]cAMP binding to purified AdoHcyase from bovine kidney in comparison with the high aff...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(02)01254-6
更新日期：2002-10-15 00:00:00
abstract：:Previous studies from this lab and others have demonstrated that nitric oxide (NO) in a concentration dependent manner, modulated neutrophil and leukemic cell survival. Subsequent studies delineated importance of iNOS in neutrophil differentiation and leukemic cell death. On the contrary, role of nNOS in survival of t...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2019.113779
更新日期：2020-06-01 00:00:00
abstract：:The composition of the glycerophosphatides in pancreas and liver was studied in rats fed an ethanol-containing diet and in pair-fed controls. The fraction of arachidonoyl-containing phosphatidylinositols in pancreas was much lower in the former rats, also when the rats were starved for a final 24 hr period. This fract...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(84)90521-5
更新日期：1984-04-01 00:00:00
abstract：:a synthetic seleno-organic compound, 2-phenyl-1,2-benzoisoselenazol-3(2H)-one (PZ 51), exhibits GSH peroxidase-like activity in vitro, in contrast to its sulfur analog, PZ 25. In addition, PZ 51 behaves as an antioxidant shown by a temporary protection of rat liver microsomes against ascorbate/ADP-Fe-induced lipid per...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(84)90083-2
更新日期：1984-10-15 00:00:00
abstract：:Cathepsin K is a cysteine protease that degrades type I human collagen during bone resorption. We have expressed the recombinant human cathepsin K in Chinese hamster ovary (CHO) cells as a pre-proenzyme and demonstrated that it is processed intracellularly to an active enzyme form and that only the proenzyme form is s...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(00)00381-6
更新日期：2000-09-15 00:00:00
abstract：:The biological effects of 1-methyl-2-nitrosoimidazole (INO), the 2 electron reduction product of biologically active 1-methyl-2-nitroimidazole, were examined in HT-29 human colon cancer cells by clonogenic assay and glutathione (GSH) determination. INO was very toxic towards HT-29 cells and was equally toxic under aer...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(89)90315-8
更新日期：1989-05-15 00:00:00
abstract：:Glipentide, a second generation sulfonylurea, raised the cellular concentration of fructose 2,6-bisphosphate in isolated rat hepatocytes. Parallel to accumulating this regulatory metabolite, glipentide inhibited basal gluconeogenesis and increased the rate of L-lactate production, as well as the metabolic flux through...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(88)90317-6
更新日期：1988-08-15 00:00:00
abstract：:Administration of phenobarbital to chick embryos increased hepatic microsomal UDP-glucuroyltransferase activity some 25-fold. The large phenobarbital-induced increase of UDP-glucuronyltransferase activity was correlated to an equivalent increase of immunochemically measurable UDP-glucuronyltransferase protein. Poly(A+...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(86)90159-0
更新日期：1986-04-01 00:00:00
abstract：:In the present work we set out to apply pharmacodynamic concepts derived from dose-response curves (Potency and Efficacy) to characterize the gene transfer efficiency of a vector:DNA complex. We employed two widely used vectors, the cationic lipid DOTAP (N,N, N-trimethyl 1-2-3-bis (1-oxo-9-octa-decenyl)oxy-(Z, Z)-1-pr...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(00)00503-7
更新日期：2000-12-15 00:00:00
abstract：:Phenothiazines (PTZ) are drugs widely used in the treatment of schizophrenia. Trifluoperazine, a piperazinic PTZ derivative, has been described as inhibitor of the mitochondrial permeability transition (MPT). We reported previously the antioxidant activity of thioridazine at relatively low concentrations associated to...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2010.06.052
更新日期：2010-10-15 00:00:00
abstract：:There is a strong association between tobacco smoking and the consumption of alcoholic beverages. When compared to the effects of either drug on its own, the combined use may lead to worsened outcomes, such as less successful quitting attempts and increased likelihood of developing mood disorders. Co-consumption most ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2017.06.113
更新日期：2017-11-15 00:00:00
abstract：:Purified ornithine decarboxylase (EC 4.1.1.17, ODC) transamidated with four putrescine moieties on four glutamine residues through the action of transglutaminase (EC 2.3.2.13, TGase) purified from guinea pig liver, when added to isolated rat liver nuclei, stoichiometrically increased the activity of RNA polymerase I (...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(82)90614-1
更新日期：1982-11-01 00:00:00
abstract：:Allosteric modulators of metabotropic glutamate receptor subtype 5 (mGlu5) represent an attractive therapeutic strategy for multiple CNS disorders. Chemically distinct mGlu5 positive allosteric modulators (PAMs) that interact with a common binding site can demonstrate biased allosteric agonism relative to the orthoste...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2020.114011
更新日期：2020-07-01 00:00:00
abstract：:Chlamydia pneumoniae is a universal pathogen that has been indicated to play a part in the development of asthma, atherosclerosis and lung cancer. The complete eradication of this intracellular bacterium is in practice impossible with the antibiotics that are currently in use and studies on new antichlamydial compound...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2010.06.051
更新日期：2010-10-15 00:00:00
abstract：:The capabilities of 1alpha, 25-dihydroxyvitamin D3 (1,25(OH)2D3), and two novel vitamin D analogues, EB1089 and KH1060, to induce the differentiation of two established leukaemia cell lines, U937 and HL-60, were assessed alone or in combination with the retinoid compounds, 9-cis retinoic acid (9-cis RA) and all-trans ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(97)00195-0
更新日期：1997-09-01 00:00:00
abstract：:DNA which has been exposed to 2-haloethylnitrosoureas has been shown to contain the chemical crosslink 1-(N3-deoxycytidyl), 2-(N1-deoxyguanosinyl)-ethane [W. P. Tong, M. C. Kirk and D. B. Ludlum, Cancer Res. 43, 3102 (1982)]. We have hypothesized that this structure is formed by an initial attack of a 2-haloethyl grou...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(83)90420-3
更新日期：1983-07-01 00:00:00
abstract：:Previous studies showed that SMA41, a 3-methyltriazene termed "combi-molecules" possessing a dual epidermal growth factor receptor (EGFR)/DNA targeting properties induced potent antiproliferative activity against alkylating-agent-resistant cells expressing EGFR in vitro. However, despite its marked potency, its antitu...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2005.04.037
更新日期：2005-08-15 00:00:00
abstract：:Rat liver microsomal 4-hydroxycoumarin binding was studied by assaying specific [14C]warfarin binding. Microsomes of warfarin-sensitive rats contained about 40 pmole of specific binding sites per mg of microsomal protein. There was no difference for R- or S-[14C]warfarin. Neither was there any difference between the e...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(89)90257-8
更新日期：1989-04-01 00:00:00
abstract：:Reactive oxygen and nitrogen species are overproduced in the cardiovascular system in response to the exposure to doxorubicin, a cardiotoxic anticancer compound. Oxidant-induced cell injury involves the activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) and pharmacological inhibition of PARP has recen...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2004.11.023
更新日期：2005-03-01 00:00:00
abstract：:Anti-angiogenic therapy mediated by drugs and food components is an established strategy for cancer prevention. Our previous cell-culture studies identified a food-derived anti-angiogenic compound, tocotrienol (T3, an unsaturated vitamin E), as a potential angiogenic inhibitor. Among T3 isomers, delta-T3 is considered...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2008.05.017
更新日期：2008-08-01 00:00:00
abstract：:Vindesine biotransformation was investigated using a bank of human liver microsomes. The drug was converted into one major metabolite (M) upon incubation with the microsomes. Large interindividual variations were observed: vindesine biotransformation rates ranged from 1.2 to 12.9 pmol/min/mg protein. Vindesine metabol...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90169-w
更新日期：1993-02-24 00:00:00
abstract：:Blood samples from 140 healthy German volunteers were used to further characterize the genetic polymorphism of the human theta class glutathione S-transferase 1 (GSTT1). For measurements of GSTT1 activity, hemolysates were incubated in vitro with different concentrations of dichloromethane. The resulting enzymatically...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(98)00191-9
更新日期：1998-11-01 00:00:00
abstract：:The dithiol-reducing thioredoxin/thioredoxin reductase system normally maintains the reduced state of key enzymes responsible for the cell's anti-oxidant defences. We therefore addressed the question of whether AW 464--a novel thioredoxin inhibitor--as well as broad spectrum dithiol ligands diamide and phenylarsine ox...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(03)00471-4
更新日期：2003-11-01 00:00:00
abstract：:Antioxidant and anti-inflammatory therapy approaches have been in the focus of attention in the treatment of neurodegenerative Parkinson's and Alzheimer's diseases where oxidative stress has been implicated. Tea extracts have been previously reported to possess radical scavenger, iron chelating and anti-inflammatory p...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(01)00813-9
更新日期：2002-01-01 00:00:00
abstract：:The formyl peptide receptor (FPR) gene family has a complex evolutionary history and comprises eight murine members but only three human representatives. To enable translation of results obtained in mouse models of human diseases, more comprehensive knowledge of the pharmacological similarities/differences between the...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2016.09.004
更新日期：2016-11-01 00:00:00
