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PubMed1995

Onlay silicone and hydroxyapatite-tricalciumphosphate composite (HAP-TCP) blocks interfere with nasal bone growth in rabbits.

We investigated how a new type of synthetic porous hydroxyapatite ceramic (HAP-TCP) acts when it is implanted in growing membranous bone. Seventy-six New Zealand White infant male rabbits (4-week-olds) were used. Rabbits received HAP-TCP block or silicone block implantation in their right nasal bone. The left nasal bone was used for a sham. Serial or cross-sectional examinations by morphometry, radiology, blood biochemistry, and histology were carried out. Both the HAP-TCP and silicone groups exhibited no systemic growth disturbance in terms of morphometry and blood biochemistry. Dual energy x-ray absorptiometry (DEXA) revealed, however, a decrease in the bone mineral content (BMC) of the right nasal bone in the silicone group. Histology revealed a superior affinity of HAP-TCP to bone tissue than that of silicone. When a HAP-TCP block was implanted under the periosteum it bonded directly to bone tissue. However, sinking of the implants into the bone tissue were noted both in the HAP-TCP and the silicone groups in longitudinal observation. These results suggest that although HAP-TCP has superior affinity to bone tissue, this by itself is not enough sufficient reason to believe that HAP-TCP can be effectively applied during the growth period.

Absorptiometry, Photon↗
PubMed1998

FPP modulates mammalian sperm function via TCP-11 and the adenylyl cyclase/cAMP pathway.

Fertilization promoting peptide (FPP; pGlu-Glu-ProNH2), which is found in seminal plasma, promotes capacitation but inhibits spontaneous acrosome loss in mammalian spermatozoa in vitro. Adenosine, known to modulate the adenylyl cyclase (AC)/cAMP pathway, elicits these same responses whereas FPP + adenosine produces an enhanced response, leading to the hypothesis that FPP and adenosine modulate the same signal transduction pathway but act via different receptors. TCP-11, the product of a t-complex gene, is the putative receptor for FPP: Fab fragments of anti-TCP-11 antibodies have the same effect as FPP on mouse spermatozoa and Gln-FPP, a competitive inhibitor of FPP, also competitively inhibits responses to the Fab fragments. In the present study, specific binding of 3H-FPP to sperm membranes was significantly inhibited by 200 nM Gln-FPP and anti-TCP-11 Fab fragments (1/25 dilution), thus confirming that FPP, Gln-FPP, and Fab fragments compete for the same binding site. In addition, spermatozoa treated with A23187 to induce the acrosome reaction bound significantly less 3H-FPP than untreated cells, suggesting that a large proportion of the FPP binding sites are associated with the acrosomal cap region; TCP-11 is located in this region. In other experiments, 100 nM FPP significantly stimulated cAMP production in mouse sperm membranes, permeabilized cells and intact cells. Furthermore, Gln-FPP inhibited production of cAMP in response to FPP but not to adenosine (10 microM) or its analogue NECA (100 nM), supporting the involvement of two different receptors. Finally, anti-TCP-11 Fab fragments (1/25 dilution) significantly stimulated cAMP production, whereas low Fab (1/200; nonstimulatory when used alone) plus adenosine (10 microM) significantly enhanced the stimulation of capacitation by adenosine. These results support the hypotheses that TCP-11 is the receptor for FPP and that FPP<-->TCP-11 interactions modulate AC/cAMP.

Adenosine↗
PubMed2001

Degradation of 2,4,6-trichlorophenol (2,4,6-TCP) by co-immobilization of anaerobic and aerobic microbial communities in an upflow reactor under air-limited conditions.

The co-immobilization and the culture of anaerobic and aerobic communities was tested for the mineralization of 2,4,6-trichlorophenol (2,4,6-TCP). At first, the anaerobic microorganisms (aggregated into granules) were cultivated in an upflow anaerobic sludge blanket (UASB) reactor, in a continuous mode, with glucose, propionate, acetate (COD loading rate = 0.5-2.0 g COD/l per day, ratio 1:1:1) and 2,4,6-TCP (2,4,6-TCP loading rate = 25-278 micromol/l per day) as substrates. 2,4,6-TCP was degraded into 2,4-DCP and 4-CP, but it was not mineralized because of the low degradation rates of 4-CP. Furthermore, the highest loading rates of 2,4,6-TCP (>126 micromol/l per day) caused the inhibition of the strains degrading the propionate. The granules were therefore tested in association with the aerobic community. They were immobilized in kappa-carrageenan/gelatin [2% (w/w) of each polymer] gel beads and cultivated in a reactor, on their own (to test the influence of the gel), and then with the aerobic community, under anaerobic and air-limited conditions, respectively. The results showed that (1) the gel did not influence the activity of the granules, (2) the anaerobic and aerobic communities could be easily co-immobilized in gel beads and cultivated in a reactor, (3) the mineralization of 2,4,6-TCP (2,4,6-TCP loading rate = 10-506 micromol/l per day), its intermediates of degradation and the other substrates [glucose + acetate + propionate (ratio 1:1:1) = COD loading rate = 500 mg COD/l per day] could be obtained under air-limited conditions if the culture parameters were strictly controlled [airflow = 36-48 vvd (volume of air/volume of liquid in the reactor per day), pH value at around 7.5]. Finally, the gel did not retain its structure during the whole culture (263 days) in the air-limited reactor, but the anaerobic and aerobic communities retained their activities and worked together for the mineralization.

Bacteria, Aerobic↗
PubMedDate not supplied

Effects of TCP on spatial memory: comparison with MK-801.

TCP (N-[1-(2-thienyl)cyclohexyl]piperidine), A PCP (phencyclidine) derivative, has been shown to possess antiepileptic and neuroprotective efficacy against chemically induced seizures. However, it is known that other antagonists of the NMDA receptor impair spatial learning. This study was thus undertaken to explore the eventual effects of TCP on memory. The same study was done with MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine ), one of the most studied NMDA receptor antagonists, which can be considered as a reference molecule. Three doses of each drug were chosen: 0.05, 0.1, and 0.2 mg/kg for MK-801 and 0.5, 1, and 2 mg/kg for TCP, the second dosage corresponding to the minimal required for antiseizure activity. The drugs were injected IP 30 min each day before a classical procedure of acquisition in a Morris water maze test. At the highest dose of each drug, the animals did not learn the position of the platform. At 0.1 mg/kg MK-801, the rats used a praxis strategy to find the platform but they did not known where the platform was. Contrary to MK-801, TCP at 1 mg/kg did not induce any memory impairment. At the lowest doses used, no memory impairment was found. It thus appears that, at the minimal therapeutic dose effective against chemically induced seizures (0.1 mg/kg for MK-801 and 1 mg/kg for TCP), TCP, contrary to MK-801, does not induce any memory impairment. Furthermore, at all the doses used, TCP presents the particularity that its locomotor side effects are not long lasting, being no longer observed from 30 min after the injection.

Animals↗
PubMed1993

2,4,6-Trichlorophenol (TCP) induces chromosome breakage and aneuploidy in vitro.

2,4,6-Trichlorophenol (2,4,6-TCP), a non-mutagen to Salmonella, was reportedly negative in tests for chromosome breakage in vitro, but did produce numerical chromosome changes and micronuclei in V79 cells (Jansson and Jansson, 1992). This apparent specific ability to induce aneuploidy is of interest since aneuploidy testing is not part of routine genotoxicity test procedures. Here we show 2,4,6-TCP clearly induces structural chromosome aberrations in CHO cells and in V79 cells using a 3-h treatment and 20-h sampling time (17-h recovery). The isomers 2,4,5- and 2,3,6-TCP were also clastogenic in this protocol. There was no increase in aberrations when we used the protocol of Jansson and Jansson (1992), i.e., a 24-h treatment with sampling either immediately, or with a 24-h recovery period. However, positive results were obtained when a recovery time of 4-12 h was allowed after the 24-h treatment with 2,4,6-TCP. Previous negative aberration tests of 2,4,6-TCP (Galloway et al., 1987; Ishidate, 1988) are also likely due to inappropriate protocols. All these results were obtained without S9 metabolic activation. We also found positive results in CHO cells when 2,4,6-TCP was tested with S9. The present study demonstrates that 2,4,6-TCP induces both structural and numerical aberrations, and underscores the importance of protocol design, in particular the appropriate recovery time after treatment, for detecting clastogenic activity in vitro.

Aneuploidy↗
PubMed1991

Cloning of cDNA encoding rat TCP-1.

We have isolated and sequenced a cDNA encoding a rat homolog of the mouse t-complex polypeptide 1 (TCP-1). Its deduced gene product is a polypeptide of 556 amino acids, with a predicted Mr of 60,341. The similarity between mouse Tcp-1 and the rat homolog is about 94.0% at the nucleotide level and 97.1% at the amino acid level showing the evolutionary conservation of this protein. The similarity of the amino acid sequence of the rat TCP-1 is not significantly biased to any of those from wild (TCP-1B) or from t-haplotype mice (TCP-1A). From a comparison of deduced amino acid sequences of eukaryotic TCP-1 proteins, we found highly conserved domains. Southern blot analysis revealed that there are at least two similar sequences to Tcp-1 in the rat, one is a structural gene and the other seems to be a processed pseudogene.

Amino Acid Sequence↗
PubMed2005

Acrylic bone cements modified with beta-TCP particles encapsulated with poly(ethylene glycol).

Beta-tricalcium phosphate (beta-TCP) has been encapsulated with poly(ethylene glycol) (PEG) to improve the filler/cement interface, and it was later incorporated to a poly(methyl methacrylate) bone cement in order to obtain cements with improved stability in the long term. Size and size distribution of the agglomerates forming the initial powder was drastically changed after its dispersion in a PEG aqueous solution. Whereas the initial beta-TCP particles had a 584 microm average diameter, the treated particles (TCP-PEG) presented more than 60% of the particles in a range of 2-6 microm. The effect of adding the treated particles to an acrylic cement was evaluated in terms of curing parameters, in vitro behaviour and mechanical performance. The presence of the TCP-PEG particles did not affect either peak temperature or setting time, indicating a good homogeneity of polymerising mass in contrast to the effect observed with the plain beta-TCP particles, which gave rise to higher setting times. In vitro behaviour studies revealed hydration degree values of the modified cements comparable to that of PMMA cements. Early stages of water uptake was Fickian in nature for all the experimental formulations indicating that the water absorption followed a diffusion controlled mechanism. After 3 months of storage in SBF the experimental formulations presented values of compressive strength in the range 76-78 MPa, higher than the minimum required by ISO 5833 (70 MPa) and those of tensile strength in the range 42-48 MPa, higher than the minimum reported for commercial formulations (30 MPa), but no significant differences in the strengths and elastic modulus were observed with the treatment of the filler particles. This observation was confirmed by ESEM analysis of the tensile fracture surfaces, which revealed a rather good cohesion between the bioceramic particles with some gaps around them, independently of the type of particles. The themogravimetric analysis of dry and wet specimens showed a higher dissolution rate of the plain beta-TCP particles in comparison to the encapsulated ones, indicating that the PEG adsorbed on the surface of the TCP particles could be a way to control the resorbability of the bioceramic component.

Absorption↗
PubMed2002

TCP is hardly resorbed and not osteoconductive in a non-loading calvarial model.

Tricalciumphosphate (TCP) has been used as a ceramic bone substitute material in the orthopedic field as well as in craniofacial surgery. Some controversies exist concerning the osteoconductive potential of this material in different implantation sites. This study was designed to evaluate the biological response of calvarial bone towards TCP granules under non-loading conditions to assess the potential of TCP as a biodegredable and osteoconductive bone substitue material for the cranial vault. Full-thickness non-critical size defects were made bilaterally in the calvaria of 21 adult Wistar rats. One side was filled by TCP granules, the contralateral side was left empty and used as a control. Animals were sacrified in defined time intervals up to 6 months. Bone regeneration was analyzed with special respect toward the micromorphological and microanalytical features of the material-bone interaction by electron microscopy and electron diffraction analysis. Histologic examination revealed no TCP degradation even after 6 months of implantation. In contrast, a nearly complete bone regeneration of control defects was found after 6 months. At all times TCP was surrounded by a thin fibrous layer without presence of osteoblasts and features of regular mineralization. As far as degradation and substitution are concerned, TCP is a less favourable material tinder conditions of non-loading.

Animals↗
PubMed2002

Promotion of bone formation using highly pure porous beta-TCP combined with bone marrow-derived osteoprogenitor cells.

Beta-tricalcium phosphate (TCP) exhibits rapid degradation and weak mechanical properties, which has limited its application as bone graft substitutes, though it has good biocompatibility and osteoconductivity. We hypothesized that a composite of highly pure porous beta-TCP and bone marrow-derived osteoprogenitor cells (BMO) could improve bone formation, and slow down the degradation of beta-TCP. A highly pure porous beta-TCP with 75% porosity was fabricated. The pores averaged 200-400 microm in diameter, with interconnecting paths 100-200 microm. Blocks of beta-TCP 5 mm3 were combined with BMO, and incubated 2 weeks with (+) or without (-) osteogenic medium. They were then implanted into subcutaneous sites of syngeneic rats for 24 weeks. These composites were harvested at different time points. The alkaline phosphatase activity and bone osteocalcin content of the composites (+) were much higher than corresponding values in the composites (-) of the control group (p<0.01). Light microscopy revealed mature bone and lots of blood vessels only in the TCP/BMO composite (+). The amount of newly formed bone increased until week 24. Slow resorptive activity could be found. The mechanical parameters of the composites were much improved over those of dry beta-TCP blocks. These results showed that tissue engineering treatment on incubating the composites of beta-TCP and BMO cells in osteogenic medium results in a good osteogenic activity.

Alkaline Phosphatase↗
PubMed1997

The tcp gene cluster of Vibrio cholerae.

The toxin co-regulated pilus (TCP) has been identified as a critical colonization factor in both animal models and humans for Vibrio cholerae O1. The major pilin subunit, TcpA (and also TcpB), is similar to type-4 pilins but TCP probably more appropriately belongs to a sub-class which includes the bundle-forming pilus of enteropathogenic Escherichia coli. The genes for TCP biosynthesis and assembly are clustered with the exception of housekeeping functions such as TcpG (=DsbA, a periplasmic disulfide bond epimerase). The nt sequences from El Tor and classical strains show only minor differences corresponding to the major regulatory regions and in TcpA itself. These differences are thought to account for the alternate conditions required for expression of TCP by the two biotypes and the antigenic variation and lack of cross-protection. Aside from the TcpA only a few of the proteins have had their roles in TCP biogenesis defined. Regulation of TCP is controlled by the ToxR regulon via ToxT with a possible involvement of TcpP and the cAMP-CRP system. Experiments using the infant mouse cholera model have now shown that TCP is a colonization factor and protective antigen for both classical and El Tor O1 strains and in the O139 Bengal serotype and that the mannose-sensitive haemagglutinin pilus does not appear to play a comparable role.

Amino Acid Sequence↗
PubMed2003

Sinus floor augmentation with beta-tricalciumphosphate (beta-TCP): does platelet-rich plasma promote its osseous integration and degradation?

When dental implants are to be inserted, sinus floor augmentation is an effective treatment procedure to improve bone height in the posterior maxilla. In addition to autogenous bone material, allogenic materials, e.g. beta-tricalciumphosphate (beta-TCP), have been used successfully. The purpose of this study was to investigate whether the combination of beta-TCP with platelet-rich plasma (PRP) enhances bony regeneration and resorption of the tricalciumphosphate material. In a randomized prospective trial, 45 sinus floor elevations were performed in 39 patients. In 22 sites, PRP was added to the beta-TCP granules, while in 23 sites beta-TCP without PRP was used. Six months later, bone specimens were harvested from the augmented region during the implant insertion procedure. The formation of new bone was about 8-10% higher when PRP was applied. A faster degradation of the ceramic bone substitute was not observed. In conclusion, when PRP was added to beta-TCP, bone regeneration was supported to a small extent. However, the resorption of beta-TCP was not accelerated and foreign-body giant cells and soft tissue surrounding the beta-TCP granules were present.

Absorbable Implants↗
PubMed1993

Cloning and characterization of the Salmonella typhimurium-specific chemoreceptor Tcp for taxis to citrate and from phenol.

Salmonella typhimurium shows an attractant response to citrate and a repellent response to phenol, and a chemoreceptor mediating these responses has been identified and named Tcp (taxis to citrate and away from phenol). Tcp is one of the methyl-accepting chemotaxis proteins that have a molecular mass of approximately 60 kDa estimated by SDS/PAGE, and its methylation level is increased by citrate and decreased by phenol. Tcp also mediates an attractant response to metal-citrate complexes. The complete nucleotide sequence of the tcp coding region has been determined. The deduced amino acid sequence of Tcp, consisting of 547-amino acid residues, is homologous with that of the aspartate chemoreceptor of S. typhimurium. Thus, Tcp is another member of the bacterial transmembrane chemoreceptor family. Because citrate is a good carbon source for S. typhimurium but is not a carbon source for the closely related species Escherichia coli and because citrate utilization is used as a key diagnostic character to distinguish these species, it is reasonable to assume that Tcp is specific to S. typhimurium.

Amino Acid Sequence↗
PubMed2006

Fundamental form of a population TCP model in the limit of large heterogeneity.

A population tumor control probability (TCP) model for fractionated external beam radiotherapy, based on Poisson statistics and in the limit of large parameter heterogeneity, is studied. A reduction of a general eight-parameter TCP equation, which incorporates heterogeneity in parameters characterizing linear-quadratic radiosensitivity, repopulation, and clonogen number, to an equation with four parameters is obtained. The four parameters represent the mean and standard deviation for both clonogen number and a generalized radiosensitivity that includes linear-quadratic and repopulation descriptors. Further, owing to parameter inter-relationship, it is possible to express these four parameters as three ratios of parameters in the large heterogeneity limit. These ratios can be directly linked to two defining features of the TCP dose response: D50 and gamma50. In the general case, the TCP model can be written in terms of D50, gamma50 and a third parameter indicating the ratio of the levels of heterogeneity in clonogen number and generalized radiosensitivity; however, the third parameter is unnecessary when either of these two sources of heterogeneity is dominant. It is shown that heterogeneity in clonogen number will have little impact on the TCP formula for clinical scenarios, and thus it will generally be the case that the fundamental form of the Poisson-based population TCP model can be specified completely in terms of D50 and gamma50: TCP= 1/2 erfc[square root of pi(gamma50)(D50/D-1)]. This implies that limited radiobiological information can be determined by the analysis of dose response data: information about parameter ratios can be ascertained, but knowledge of absolute values for the fundamental radiobiological parameters will require independent auxiliary measurements.

Journal Article↗
PubMed2004

[Experimental study of porous TCP to generate tissue-engineered long bone].

To study bone-forming of a new kind of porous beta-TCP as the scaffold for tissue-engineering, defects at the mid-portion of the left and right ulna were created in dog, the defects were repaired with beta-TCP cylinder coated with BMSCs, and beta-TCP cylinders alone as control. X-rays showed the defects were better bridged by the replant with obscure edge and new bone formed in the canal and at the interface in experimental group after three month of operation, whereas in control group, the replants were obviously deformed into dissociated granule with unequal density with only little new bone formed at the interface. After six month, the defects were bridged by new bone with osteodermatous cavum medullare ossium, but in control group, the defects were bridged by high density in radiography without osteodermatous cavum medullare ossium, the diameter of the ular was obviously less than experimental group. There were significant differences between both groups at month one and two in the development pattern through radionuclide observation. By gross, the diameter of ular was smaller in control group than in experimental at month three, and the replants in control group was difficult to detach from the fibroid tissue around it, but in experimental group, there was much more new bone formation, and the surface was rough for the compound of new bone and beta-TCP undegraded completely. The new bone in experiment had been obviously remodeled at month six, but at this moment, the new bone was of infirmity in volume and form. HE staining of three months demonstrated new bone adhered to the surface on the core of beta-TCP in experimental group, but in control group, at the same place, osteoid was observed with much megacayocytes and capillaries. At month six, beta-TCP disappeared completely with new bone formed in both groups, but the volume and structure of the bone was better in experimental group than in control group. From this study it is concluded that the porous beta-TCP can be combined with BMSCs, and the combination could generate new bone to repair long bone defect.

Animals↗
PubMed1989

TCP binding: a tool for studying NMDA receptor-mediated neurotransmission in kindling.

Findings from numerous pharmacological and electrophysiological studies have uniquely implicated the N-methyl-D-aspartate (NMDA) receptor in kindling. Recent findings indicate that this receptor is regulated by ligands acting at both amino acid (NMDA and glycine) and ion (Zn++ and Mg++) binding sites. To examine the role of the NMDA receptor in kindling it will be necessary to understand how ligands for these different binding sites interact to control activation of the NMDA receptor. To this end we examined a biochemical tool for measuring opening of the NMDA receptor-gated ion channel (NMDA channel). [3H]N-(1-[thienyl] cyclohexyl)piperidine (TCP) binding to brain membranes is stimulated by NMDA and glycine receptor agonists. We have shown that NMDA and glycine increase TCP binding by increasing the access of TCP to its site. Moreover, the pharmacology of the NMDA and glycine binding sites regulating TCP binding is identical to that of the sites regulating NMDA evoked currents. These findings strongly suggest that glycine and NMDA regulate TCP binding by increasing the opening of the NMDA channel. That is NMDA and glycine increase the overall time that the channel is open thereby increasing the time available for TCP to diffuse to its binding site. These findings support the use of TCP binding (association rate) as a marker of channel opening and thereby permit measurement of NMDA receptor activation and ligand binding under identical conditions. This will allow direct testing the hypothesis that an alteration in the NMDA receptor/channel complex itself underlies the increased seizure response of kindled animals.

Animals↗
PubMed1995

[Trigono-cervico-prostatotomy (TCP) versus transurethral resection of the prostate (TURP). Our experience].

OBJECTIVE: Trigonocervicoprostatotomy (TCP) has been considered up to now an alternative treatment to transurethral resection of the prostate (TURP) when evaluating the size of the prostate. This paper demonstrates that endoscopic visualization is more important when choosing the surgical procedure and that both techniques can achieve satisfactory results. METHODS: The prostate volume is evaluated by ultrasound and according to the endoscopic findings, TURP or TCP is performed. The prostatic lobes are routinely biopsied if the latter procedure is chosen. RESULTS: We compared the results of 34 TCP and 30 TURP procedures using the values of I-PSS and uroflowmetry before and after surgery. In 86.2% of the TCPs and 80% of the TURPs, the patients are asymptomatic with I-PSS less than 7 and significantly improved uroflowmetry data. Biopsy disclosed adenocarcinoma in one patient submitted to TCP. CONCLUSIONS: TCP represents an alternative to TURP not only for small prostates (30 gm) but also for medium-sized prostates (50-60 gms), depending on the endoscopic findings. TCP is not indicated for lateral lobes that fall on the prostate floor. Performing a biopsy routinely in TCP does not prolong the operating time significantly and permits detecting subclinical adenocarcinoma of the prostate.

Aged↗
PubMed1997

[Possibility of alpha-tricalcium phosphate (alpha-TCP) particles as a drug carrier for treatment of abdominal carcinomatosis].

It is reported that cancer foci are unevenly distributed in abdominal carcinomatosis after intraperitoneal inoculation of cancer cells in rats. The organs may be briefly classified into two groups in terms of the deposit of cancer cells: one that shows an affinity to the cells includes the greater omentum, mesenterium, and gonadal fat and etc., and the other having lesser affinity the stomach, intestine, and spleen and etc. Such uneven distributions are likely to occur in clinical cases of abdominal carcinomatosis resulting from progressive digestive cancers. We have explored the possibility of alpha-Tricalcium Phosphate (alpha-TCP) particles as a drug carrier in which carboplatin (CBDCA) was incorporated. alpha-TCP, which has chemically similar properties to hydroxyapatite, is known to have an excellent biocompatibility with human tissues and is biodegradable. The present study focused on the localization and the forms of alpha-TCP particles, and the morphological changes of the surrounding tissues after intraperitoneal administration using normal and cancer-bearing rats. The following results were obtained: (1) alpha-TCP particles were taken up to a large extent in the "milky spot" of the greater omentum, followed by the "stomata" of the mesenterium, gonadal fat, diaphragm, peritoneum, and liver in normal rats. No alpha-TCP particles were caught up in the tissues of the stomach, small intestine, colon, and spleen. The margination and emigration of lymphocytes were slightly observed around those organs. (2) alpha-TCP particles were predominantly detected on the cancer mass of the greater omentum in abdominal carcinomatosis-bearing rats. It should be noted that the particles collected in the same place where cancer cells were caught, suggesting that the localization of the drug-containing particles result in higher drug concentrations in the cells possibly for extended times. The alpha-TCP particles system is expected to be a good candidate for targeting chemotherapy and specially for abdominal carcinomatosis.

Abdominal Neoplasms↗
PubMed2006

Caveolin-1 interacts with the chaperone complex TCP-1 and modulates its protein folding activity.

We report that caveolin-1, one of the major structural protein of caveolae, interacts with TCP-1, a hetero-oligomeric chaperone complex present in all eukaryotic cells that contributes mainly to the folding of actin and tubulin. The caveolin-TCP-1 interaction entails the first 32 amino acids of the N-terminal segment of caveolin. Our data show that caveolin-1 expression is needed for the induction of TCP-1 actin folding function in response to insulin stimulation. Caveolin-1 phosphorylation at tyrosine residue 14 induces the dissociation of caveolin-1 from TCP-1 and activates actin folding. We show that the mechanism by which caveolin-1 modulates TCP-1 activity is indirect and involves the cytoskeleton linker filamin. Filamin is known to bind caveolin-1 and to function as a negative regulator of insulin-mediated signaling. Our data support the notion that the caveolin-filamin interaction contributes to restore insulin-mediated phosphorylation of caveolin, thus allowing the release of active TCP-1.

Amino Acid Sequence↗