Inhibitory Effect of Plasma Fkbp12 on Immunosuppressive Activity of Fk5061,2

Shirakata, Yoshiharu; Kobayashi, Masakazu; Ohtsuka, Kazuyuki; Sugano, Motoki; Terajima, Hiroaki; Ikai, Iwao; Okajima, Hideaki; Egawa, Hiroto; Inomata, Yukihiro; Inamoto, Takashi; Tanaka, Kōichi; Yamaoka, Yoshio

doi:10.1097/00007890-199560120-00035

Cited by 13 publications

(3 citation statements)

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“…Monoclonal antibody 3F4 against a 12-kDa FK506-binding protein (FKBP12) and human recombinant FKBP12 (hFKBP12) were produced as described previously (15,16). Monoclonal antibody XA7 which reacts with RyR1 (17) and 34C which recognizes all the three mammalian RyR isoforms (18) were purchased from Upstate Biotechnology, Inc., and Affinity Bioreagents, Inc., respectively.…”

Section: Methodsmentioning

confidence: 99%

Further Characterization of the Type 3 Ryanodine Receptor (RyR3) Purified from Rabbit Diaphragm

Murayama

Ôba

Katayama

et al. 1999

Journal of Biological Chemistry

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106

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We characterized type 3 ryanodine receptor (RyR3) purified from rabbit diaphragm by immunoaffinity chromatography using a specific antibody. The purified receptor was free from 12-kDa FK506-binding protein, although it retained the ability to bind 12-kDa FK506-binding protein. Negatively stained images of RyR3 show a characteristic rectangular structure that was indistinguishable from RyR1. The location of the D2 segment, which exists uniquely in the RyR1 isoform, was determined as the region around domain 9 close to the corner of the square-shaped assembly, with use of D2-directed antibody as a probe.

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Section: Methodsmentioning

confidence: 99%

Further Characterization of the Type 3 Ryanodine Receptor (RyR3) Purified from Rabbit Diaphragm

Murayama

Ôba

Katayama

et al. 1999

Journal of Biological Chemistry

Self Cite

106

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“…FK506 and Rpm, like CsA, are metabolized by cytochrome P450 3A enzymes [115] and their level in the blood during immunosuppressive therapy can be measured using HPLC methods [116]. The plasma level of FKBP-12 may diminish the immunosuppressive potential of FK506 by sequestrating the free drug and making it inaccessible to T cells [117].…”

Section: ) the Nature Of Small Molecular Mass Molecules Interactingmentioning

confidence: 99%

Peptidylprolyl Cis / Trans Isomerases (Immunophilins): Biological Diversity - Targets - Functions

Gałat

2003

CTMC

344

302

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Information recovered from genome sequencing projects, multiple sequence alignments, structural analyses of PPIase and published records were used in deciphering the biological diversity, functions and targets of four groups of proteins encoded by dissimilar sets of sequences whose spatial representations exhibit peptidylprolyl cis/trans isomerase activity (PPIase). In the human genome there are encoded fifteen proteins whose segments have significant homology with the sequence of 12 kDa protein which is the target of the potent immunosuppressive macrolides FK506 or rapamycin. The 12 kDa archetype of the FK506-binding protein (FKBP), known as FKBP-12a, is an abundant intracellular protein whereas other FKBPs possessing from one to four FK506-like binding domains (FKBDs) have nominal masses varying from 13 to 135 kDa. The human genome contains at least sixteen genes encoding proteins comprising one cyclosporin-A (CsA) binding domain (CLD) called cyclophilins whose nominal masses vary from 17 to 324 kDa and multiple coding segments for small cyclophilins (17-19 kDa) whose transcription levels and functions remain unknown. The third group of PPIases encoded in the genome comprises two proteins (hPin1 and hParv14) where hPin1 is an important PPIase for cell cycle. The A. thaliana, C. elegans, D. melanogaster and S. cerevisiae genomes encode a less diverse spectrum of PPIases whereas the prokaryotic genomes contain from none to three cyclophilins, from none to four genes encoding FKBPs, one distant homologue of the Pin1 protein named parvulin and the fourth group of PPIases known as trigger factors. PPIases are discretely distributed to different cellular compartments and interact with a number of targets that control a range of cellular processes. Analyses of the sequence alignments of the two groups of PPIases, namely cyclophilins and FKBPs from diverse phyla, show that in each group their sequences diverge but the amino acid residues which form the PPIase activity site and macrolide binding cavity remain well conserved in the majority of them which suggests that the spatial structures and functions of each group of PPIases remain conserved.

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“…Alternatively, differences in sensitivities could be anticipated if, for example, the affinity of each drug for its respective binding protein were significantly different, or plasma levels of the binding protein, as demonstrated with FK506, increased rapidly, leading to reduced efficacy [18]. However, both CyA and FK506 are substrates for P-glycoprotein 170 (P-gp), the product of the MDRl gene in man [20,161.…”

Section: Introductionmentioning

confidence: 99%

Constitutive and acquired resistance to calcineurin inhibitors in renal transplantation: role of P-glycoprotein-170

et al. 2000

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The present study examines whether resistance to Cyclosporin A (CyA) and Tacrolimus (FK506) develops in T cells from individual patients and the role of Pglycoprotein 170 (P-gp) in mediating drug resistance. IC,,s were established for CyA and FK506 in cell cultures from 46 renal allograft recipients. P-gp expression and functional activity were determined by flow cytometry. Mean ID,, for CyA was 29 yg/li (range 2.5-100) and for FK506 1.2 yg/li (range 0.085-5.5). The sensitivities to the two drugs were correlated ( P = 0.0001). There was variation in the ratio of the ID5,+ depending on the drug used for treatment ( P = 0.02). There was no difference in P-gp expression and functional activity in patients with sensitive or resistant cells. The data indicate an association between the sensitivities to CyA and FK506 and evidence of selective resistance to whichever drug was used. P-gp drug transport does not explain this variation.

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Inhibitory Effect of Plasma Fkbp12 on Immunosuppressive Activity of Fk5061,2

Cited by 13 publications

References 0 publications

Further Characterization of the Type 3 Ryanodine Receptor (RyR3) Purified from Rabbit Diaphragm

Further Characterization of the Type 3 Ryanodine Receptor (RyR3) Purified from Rabbit Diaphragm

Peptidylprolyl Cis / Trans Isomerases (Immunophilins): Biological Diversity - Targets - Functions

Constitutive and acquired resistance to calcineurin inhibitors in renal transplantation: role of P-glycoprotein-170

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