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129 巻, 11 号
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芝崎 誠司, 植田 充美2009 年 129 巻 11 号 p. 1275-1276
発行日: 2009/11/01
公開日: 2009/11/01
ジャーナル フリーPDF形式でダウンロード (188K) -
植田 充美2009 年 129 巻 11 号 p. 1277-1284
発行日: 2009/11/01
公開日: 2009/11/01
ジャーナル フリーTo demonstrate the practical use of a novel high-throughput screening system by single cells constructed by the molecular display method, a yeast cell chip microchamber array was developed. As applications, peptides, peptidases, and antibodies were examined. Neurolysin originally recognizes substrates with six-amino-acid-long residues, cleaving a peptide bond in the center position of the substrate amino acid sequence. To alter the recognition of the P2' amino acid of substrates by neurolysin, six residues of neurolysin which might be involved in the formation of the neurolysin S2' subsite were individually and comprehensively substituted by semirational mutagenesis coupled with the yeast molecular display system. The protein libraries of mutant neurolysins were displayed on the yeast cell surface and screening was carried out using two fluorescence-quenching peptides, the matrix metalloproteinase-2/9- and MMP-3-specific substrates. Among mutant neurolysins, one mutant neurolysin with a marked change in substrate specificity was successfully obtained. Furthermore, skillful display of antibodies (H and L chains) on the cell surface of yeast cells suggested the possibility of new approach for the creation of tailor-made proteases beyond limitations of the traditional immunization approach. Accordingly, the combination of the molecular display and combinatorial bioengineering would lead to produce novel medicines.
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田丸 浩2009 年 129 巻 11 号 p. 1285-1293
発行日: 2009年
公開日: 2009/11/01
ジャーナル フリーThe main challenge of the post-genomic era is to functionally characterize genes identified by the genome sequencing projects. Model organisms, including zebrafish (Danio rerio), are indispensable for this demanding task. Zebrafish has recently been successfully incorporated into large-scale genetic screens due to the optical clarity of the embryos and their accessibility to various experimental techniques throughout development. The attractiveness of the zebrafish as a model organism is enhanced by the biological availability of continuously improving genomic tools and methodologies for functional characterization of the genes. In addition, transparent zebrafish embryos are well suited to manipulations involving DNA or mRNA injection, cell labeling, and transplantation. Once the scheduled zebrafish genome project is complete, targeted genetic manipulations in zebrafish would be able to become even more desirable. In my laboratory, we propose that the “embryoarray technology” supports to characterize especially unknown proteins using zebrafish embryos which offer a platform for assessing the biological effects by not only chemical compounds including medical drugs, siRNAs (small interfering RNAs) and micro RNAs, but foreign genes that are never existing in zebrafish. Thus, zebrafish offers a high-quality, high-throughput bioassay tool for determining the biological effect of small molecules as well as for dissecting biological pathways. In this review, I would like to introduce a couple of recent data that we have constructed the gene expression system in zebrafish and have succeeded to produce several membrane-associated proteins. Furthermore, several tools with zebrafish embryos are available to examine the interactions between protein-protein using fully automatic high-throughput microinjection system.
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芝 清隆2009 年 129 巻 11 号 p. 1295-1302
発行日: 2009/11/01
公開日: 2009/11/01
ジャーナル フリーMotif-programming is a method for creating artificial proteins by combining functional peptide motifs in a combinatorial manner. Motifs are often short amino acid sequences within natural proteins that are associated with particular biological functions. Motifs also can be created de novo using molecular engineering. In particular, peptide aptamers, which have been isolated as specific binders against various targets, are believed to be promising motif blocks for creating novel biomaterials through motif-programming. It is now known, however, that simple arithmetic addition does not always work with motif-programming-e.g., simple conjugation of motifs-A and -B does not always result in a bifunctional peptide-AB. To solve this nonlinearity in motif-programming, we have been employing a combinatorial approach, which we called MolCraft. In MolCraft, we prepare a library of artificial proteins that contain multiple motifs in various numbers and orders, from which clones having the desired functions are selected. In MolCraft, a microgene is first rationally designed so that the encoded peptides contain motifs, and then tandemly polymerized with insertion or deletion mutations at the junctions between microgene units. Because of junctional perturbations, proteins translated from a single microgene polymer are molecularly diverse, originating from the combinatorics of three reading frames, and are thus combinatorial polymers of three peptides. By embedding functional motifs into different reading frames of a single microgene, combinatorial polymers of functional motifs are easily prepared. Notably, repetitiousness retained in the overall structure of proteins contributes to the formation of ordered structures, and enhances the chances of reconstituting biological activity. This method is particularly well suited for developing liaison molecules that interface between cells and inorganic materials. Examples of multifunctional artificial proteins created from this method will be introduced.
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藤井 郁雄2009 年 129 巻 11 号 p. 1303-1309
発行日: 2009/11/01
公開日: 2009/11/01
ジャーナル フリーAt present, antibodies are indisputably the most successful reagents in molecular targeting therapy. However, use of antibodies has been limited due to the biophysical properties and the cost to manufacture. To enable new applications where antibodies show some limitations, we have developed an alternative-binding molecule with non-immunoglobulin domain. The molecule is a helix-loop-helix peptide, which is stable against natural enzymes in vivo and is small size to be non-immunogenic. We refer it as “MicroAntibody”. The peptide is composed of three structural regions, N-terminal α-helix, C-terminal α-helix, and flexible connecting loop. In both helical regions, uncharged leucine residues were incorporated into the heptad repeat positions to dimerize the α-helices by hydrophobic interactions. Since the peptide folds by virtue of the interactions between the amino acid residues positioned inside the helix-loop-helix, the solvent-exposed, outside residues were randomized to give a library of MicroAntibodies. Here, we report the construction of the phage-displayed library and the screening of MicroAntibodies binding to cytokine receptors.
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津本 浩平, 宇井 美穂子2009 年 129 巻 11 号 p. 1311-1317
発行日: 2009/11/01
公開日: 2009/11/01
ジャーナル フリーThermodynamic analysis is an effective tool in drug design. Thermodynamic parameters of the interaction between a given ligand and its target protein can reveal the character of the ligand. In general, promising drug candidates achieve high affinity for a target protein through their contributions of both favorable enthalpy and entropy terms. It is, however, more difficult to optimize binding enthalpies than binding entropies in ligand-design; therefore, it is desirable to choose firstly a lead-compound based on its favorable binding enthalpy. In this study, we have explored the utility of this approach using anti-ciguatoxin antibody 10C9 as a model in the screening of a chemical library. We previously showed that 10C9 possesses an extraordinary large antigen-binding pocket that recognizes the antigen ciguatoxin by means of a favorable binding enthalpy. Here, among the many compounds tested, three of them could bind to the antigen-binding pocket of 10C9 with a few kcal/mol of favorable binding enthalpy. In addition, these compounds showed structural analogies with the proper antigen ciguatoxin: a comparison with other compounds which showed no favorable enthalpy change upon testing revealed that 10C9 rigorously identifies their cyclic structure and a characteristic hydroxyl group. In summary, this study demonstrates that enthalpy change is an effective index for ligand-design studies.
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吉野 知子, 松永 是2009 年 129 巻 11 号 p. 1319-1325
発行日: 2009/11/01
公開日: 2009/11/01
ジャーナル フリーMagnetic particles offer vast potential in ushering new techniques, especially in biomedical applications, as they can be easily manipulated by magnetic force. Magnetotactic bacteria synthesize nano-sized biomagnetites, otherwise known as bacterial magnetic particles (BacMPs) that are individually enveloped by a lipid bilayer membrane. BacMPs are ultrafine magnetite crystals (50-100 nm diameters) with uniform morphology produced by Magnetospirillum magneticum AMB-1. Based on our elucidations on the molecular mechanism of BacMP formation in M. magneticum AMB-1, functional nanomaterials have been designed. Through genetic engineering, functional proteins such as enzymes, antibodies, and receptors were successfully displayed onto BacMPs. Here, display techniques of functional proteins onto nano-sized BacMPs and its applications to ligand binding assays were described. Dopamine receptor, which is a member of G protein-coupled receptors, was successfully displayed onto BacMPs. This system makes possible the convenient acquisition of the native conformation of membrane proteins without the need for detergent solubilization, purification and reconstitution after cell disruption. Furthermore, estrogen receptor, which is one of nuclear receptors, was also displayed onto BacMPs. The assay using BacMPs displaying estrogen receptor could discriminate full agonists, partial agonists, or antagonists. The elucidation of the mechanism of BacMP synthesis has provided a roadmap for the design of novel nano-biomaterials that would play a useful role in multidisciplinary fields.
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瀬脇 智満2009 年 129 巻 11 号 p. 1327-1332
発行日: 2009/11/01
公開日: 2009/11/01
ジャーナル フリーLactic acid bacteria (LAB) are a group of Gram-positive, and generally recognized as safe bacteria. LAB have been used as the starter for the fermentation food (i.e., cheese, yoghurt and kimuchi etc.). On the other hand, several studies of LAB as delivery vehicles have focused on the generation of mucosal vaccine. We have developed novel surface display system based on PgsA gene, which isolated from Bacillus subtilis chungkookjang. We introduce the Lactobacillus surface display system by using the PgsA anchor protein and its application. HPV oncogene, E7, is a reliable target protein since E7 is expressed in the CIN lesion. Although many studies have demonstrated these vaccines elicit systemic immune responses to HPV E6/E7, few studies have shown mucosal immune responses. There is no therapeutic vaccine utilizing oral administration and there is no clinical trial which addresses cervical mucosal cellular immune responses to the vaccine. Our recent progress is production of a mucosal vaccine to treat cervical intraepithelial neoplasia (CIN) that has potential of cervical cancer. The vaccine is expected to help the vast number of women suffering from high grade CIN. Lac-E7 is a candidate for new therapeutic vaccine for cervical intraepithelial neoplasia.
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芝崎 誠司2009 年 129 巻 11 号 p. 1333-1340
発行日: 2009/11/01
公開日: 2009/11/01
ジャーナル フリーTechniques for immobilizing proteins on surface of virus or microorganisms, namely molecular display technologies, have played important roles in helping the elucidation of protein-protein interactions in cells and to develop research on drug discovery. Phage display system is well-established and sophisticated; consequently, bioactive low-molecular-weight ligands and proteins significant in pharmaceutical industry have been found. In addition to the development of novel functional proteins by phage display using results from experiments in genomics and proteomics, ribosome display or yeast display systems have been developed as complementary methods. We can select the appropriate method on the basis of the objective. Molecular display using yeast has advantages in production of desired proteins from combinatorial library by flow cytometry. Firstly, principle, development procedure, and latest research in this field are introduced. Thereafter, results of molecular display using yeast for antibodies and their related proteins are presented. Furthermore, display of receptor coupled with intracellular signal transduction —a novel type of molecular display on yeast cell surface— has been created in recent years. The role and potential of molecular display technologies employing yeast cells in drug discovery are discussed.
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総説
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板垣 史郎2009 年 129 巻 11 号 p. 1341-1349
発行日: 2009/11/01
公開日: 2009/11/01
ジャーナル フリーOral drug delivery is generally the most desirable means of administration, mainly because of patient acceptance, convenience in administration. Intestinal absorption mechanisms of anionic drugs have been mainly explained by the passive diffusion of nonionized compounds. However, several studies have suggested the involvement of specific transporters in intestinal absorption of weak acids including monocarboxylates. (−)-N-(trans-4-Isopropylcyclohexanecarbonyl)-D-phenylalanine (nateglinide) is a oral hypoglycemic agent possessing a carboxyl group and a peptide-type bond in its structure. Although nateglinide quickly reaches the maximal serum concentration after oral administration, nateglinide itself is not transported by PepT1 or MCT1. We demonstrated that nateglinide transport occurs via a single system that is H+ dependent but is distinct from PepT1 or MCT1. In clinical, patients usually take many kinds of drugs at the same time. Thus, drug-drug interactions involving transporters can often directly affect the therapeutic safety and efficacy of many drugs. However, there have been few studies on food-drug interactions involving transporters. Dietary polyphenols have been widely assumed to be beneficial to human health. Polyphenols are commercially prepared and used as functional foods. We reported that ferulic acid, which is widely used as a functional food, affects the transport of clinical agents. The major dose-limiting toxicity after administration of irinotecan hydrochloride, 7-ethyl-10-(4-[1-piperidino]-1-piperidino)-carbonyloxycamptothecin (CPT-11) is severe diarrhea. We have found that a specific transport system mediates the uptake of active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38) across the apical membrane in Caco-2 cells. Baicalin and sulfobromophthatlein inhibit this transporter. Inhibition of this transporter would be a useful means for reducing late-onset diarrhea.
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清水 万紀子2009 年 129 巻 11 号 p. 1351-1356
発行日: 2009年
公開日: 2009/11/01
ジャーナル フリーIndividual differences of drug-metabolizing enzymes are important determinants for the metabolic fate of chemicals. This article focuses on polymorphic human flavin-containing monooxygenase 3 (FMO3) and dietary-derived trimethylamine. Malodorous trimethylamine is generally converted to odorless trimethylamine N-oxide by liver microsomal FMO3. Trimethylaminuria is caused by functional disorder of FMO3. In this study mutations of the FMO3 gene were examined in self-reported Japanese trimethylaminuria subjects that showed low FMO3 metabolic capacity in urine tests. Nine novel polymorphisms in the FMO3 gene were discovered in self-reported Japanese volunteers. Functional analyses of recombinant FMO3 proteins suggested that these FMO3 gene mutations were one of the causal factors for decreased FMO3 function resulting in trimethylaminuria. Inter-individual variations of FMO3-mediated microsomal oxygenation activities, levels of FMO3 protein and FMO3 mRNA, and its modification in liver microsomes from Japanese samples were observed. Both genetic polymorphisms in the 5′-upstream of the FMO3 gene and some hormonal changes related to menstruation may be causal factors for inter- and/or intra- individual expression levels of FMO3. To assess the palliative cares, it was found that absorbed levels of trimethylamine in vivo would be possibly controlled by selection of precursor foods like fish containing a variety of trimethylamine amounts. These lines of evidence suggest that individual differences of FMO3 are important determinants for the metabolic fate of dietary-derived trimethylamine.
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松永 直哉2009 年 129 巻 11 号 p. 1357-1365
発行日: 2009/11/01
公開日: 2009/11/01
ジャーナル フリーThe mammalian circadian pacemaker stays in the paired suprachiasmatic nuclei (SCN). Recent several studies reveal that the circadian rhythms of physiology and behavior are controlled by clock genes. In addition, the effectiveness and toxicity of many drugs vary depending on dosing time associated with 24-h rhythms of biochemical, physiological, and behavioral processes under the control of the circadian clock. Acetaminophen (APAP) is a widely used analgesic drug, and is mainly biotransformed and eliminated as nontoxic conjugates with glucuronic acid and sulfuric acid. Only a small portion of the dose is mainly bioactivated by CYP2E1 to N-acetyl-p-benzoquinone imine (NAPQI), a reactive toxic intermediate. For APAP overdose, glucuronidation and sulfation are saturated and the formation of NAPQI increases. However, the exact mechanisms underlying the chronotoxicity of APAP have not been clarified yet. In the present study, we have clarified that there was a significant dosing time-dependent difference in hepatotoxicity induced by APAP in mice. The mechanism may be related to the rhythmicity of CYP2E1 activity and GSH conjugation. In additon, we investigated whether the liver transcription factor hepatic nuclear factor-1α (HNF-1α) and clock genes undergoing astriking 24-h rhythm in mouse liver contribute to the 24-h regulation of CYP2E1 activity. A significant 24-h rhythmicity was demonstrated for CYP2E1 activity, protein levels and mRNA levels. HNF-1α and clock genes may contribute to produce the 24-h rhythm of CYP2E1 mRNA levels. Metabolism by CYP and GSH conjugation are common metabolic pathways for many drugs such as APAP. These findings support the concept that choosing the most appropriate time of day to administer the drugs associated with metabolic rhythmicity such as CYP and GSH conjugation may reduce hepatotoxicity in experimental and clinical situations. 24-h rhythm of CYP2E1 activity was controlled by HNF-1α and clock gene, in a transcriptional level. Identification of rhythmic marker for selecting dosing time will lead improved progress and diffusion of chronopharmacotherapy.
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一般論文
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村井 ユリ子, 佐藤 真由美, 山口 浩明, 島田 美樹, 眞野 成康, 後藤 順一, 菱沼 隆則2009 年 129 巻 11 号 p. 1367-1373
発行日: 2009/11/01
公開日: 2009/11/01
ジャーナル フリーTo develop students' sensitivity toword medication hazards, we have introduced a behavioral approach, “Kiken-Yochi Training” (KYT) for hazard prediction training to pharmacy education. KYT was originally implemented in the field of occupational health and safety in Japan. Only recently it has been introduced in the medical arena. The process consists of four steps; identification of hazards, assessing risks, planning countermeasure, and making action plan. One facilitator organizes the KYT class (20 students divided into four or five small groups). Watching a photo or illustration of everyday occurrences, each group follows the above four steps to discuss predictable hazards. Concepts are intensively presented in short time with brainstorming. KYT has been used with five classes thus far. Students learned KYT theory and exhibited desired attitudes and behaviors. Students presented many ideas, then formulated their own action plan within about one hour. More than 95% of KYT-naïve students assessed themselves as capable of applying the methodology in various situations. They also assessed themselves as being more aware of potential hazards and new points of view through the KYT process. Pharmacists must work for safer and more effective pharmacotherapy, predicting hazards as side effect or human error and solving the problems on each patient. KYT is a very useful and effective tool for pro-active safety training for the skill and attitude development. Repeating problem-based learning like KYT at intervals through undergraduate education should improve patient safety.
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Branka IVIĆ, Svetlana IBRIĆ, Gabriele BETZ, Zorica DJURI&# ...原稿種別: Regular Article
2009 年 129 巻 11 号 p. 1375-1384
発行日: 2009/11/01
公開日: 2009/11/01
ジャーナル フリーThe purpose of the study was to screen the effects of formulation factors on the in vitro release profile of diclofenac sodium from matrix pellets compressed into multiple unit pellet system (MUPS) tablets using design of experiment (DOE). Extended release of diclofenac sodium was accomplished using Carbopol® 71G as matrix substance. According to Fractional Factorial Design FFD 23-1 four formulations of diclofenac sodium MUPS matrix tablets were prepared. The process of direct pelletization and subsequently compression of the pellets into tablets was applied in order to investigate a different approach in formulation of matrix systems and to achieve a better control of the process factors over the principal response - the release of the drug. The investigated factors were X1-the percentage of polymer Carbopol® 71G, X2-crushing strength of the tablet and X3-different batches of the diclofenac sodium. In vitro dissolution time profiles at 6 different sampling times were chosen as responses. Results of drug release studies indicated that drug release rates vary between different formulations, with a range of 1 to 8 h to complete dissolution. The most important impact on the drug release had factor X1-the percentage of polymer Carbopol® 71G. The polymer percentage is suggested as release regulator for diclofenac sodium release from MUPS matrix tablets. All other investigated factors had no significant influence on the release profile of diclofenac sodium.
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中井 由佳, 徳山 絵生, 吉田 都, 内田 享弘原稿種別: Regular Article
2009 年 129 巻 11 号 p. 1385-1392
発行日: 2009/11/01
公開日: 2009/11/01
ジャーナル フリーThe purpose of this study was to evaluate the incompatibility of ceftriaxone with calcium-containing products, which had been the subject of an ALERT issued by the FDA. The influence of calcium ion concentration, storage temperature and shaking on the appearance and quantity of insoluble microparticles in mixtures of the two was examined using a light obscuration particle counter and a stereomicroscope. Appropriate volumes of 2% (w/v) calcium chloride solution were added to ceftriaxone sodium for injection (10 mg/ml) to make solutions with final calcium ion concentrations of 0.5-2.5 mmol/l, and stored at 20°C, 25°C, or 30°C. The number of insoluble microparticles increased on storage when the calcium ion concentration of the sample was ≥2 mmol/l; it exceeded the permissible range at all temperatures by 1 h. The microparticles had a greater diameter at higher temperatures, although fewer microparticles were observed. The weight of precipitate increased as a function of both the calcium ion concentration and the temperature. The number of microparticles was also significantly increased by shaking. The number of microparticles in mixtures containing 1000 μg/ml ceftriaxone was significantly increased, even though concentrations of calcium ion was 1.25 mmol/l. Overall, not only calcium ion concentration, but storage temperature and shaking affected the extent of precipitation of ceftriaxone with calcium.
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赤井 那実香, 藤田(濱邊) 和歌子, 徳山 尚吾2009 年 129 巻 11 号 p. 1393-1401
発行日: 2009/11/01
公開日: 2009/11/01
ジャーナル フリーThe treatment of cancer pain requires an individually-targeted multidimensional team approach. Further, the basic act for the Anti-Cancer Measures describes that medical staff including pharmacists should participate in the palliative care. Thus it is obvious that community pharmacists should also participate in palliative home care. In addition, a misunderstanding about opioids remains strong in Japan, which could be one of the barriers to palliative home care. In our previous report, we clarified for local residents the importance of educational activity using opioids as a new role for community pharmacists, and it was recognized of great significance by these pharmacists. In this study, we conducted a questionnaire survey among medical doctors, nurses, care managers and home helpers about the need and meaning of the educational activity performed by pharmacists in palliative home care. 86.4% of respondents felt pharmacists' participation in home care was required. Furthermore, most respondents thought that misunderstanding remained about opioids in palliative home care, and believed that pharmacists could play an important role in educational activity about opioids as experts in medicine. This study clarified that other medical team members need the participation of community pharmacists in palliative home care. Therefore, it seems important for these pharmacists to be proactive in participating in such care in the future.
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Chun-Ying XIE, Wei YANG, Ming LI, Jun YING, Shu-Juan TAO, Karen LI, Ji ...原稿種別: Regular Article
2009 年 129 巻 11 号 p. 1403-1413
発行日: 2009/11/01
公開日: 2009/11/01
ジャーナル フリーThe chemical compound δ-elemene, isolated from the Chinese herbal medicine plant Curcuma Wenyujin, has been known to exert antitumor activity. In this study we demonstrated that apoptotic cell death induced by δ-elemene in DLD-1 cells was concentration-and time-dependent, and had little inhibition of the normal human liver cell line WRL-68. Apoptosis was further confirmed and quantified by DNA fragmentation ELISA, Annexin V (AnV) binding of externalized phosphatidylserine and the mitochondrial probe JC-1 using flow cytometry. The rapid increase in intracellular reactive oxygen species (ROS) levels was involved in the mechanism of cell death. Western blot analysis demonstrated that δ-elemene activated the caspase-signaling pathway, leading to the proteolysis conversion of pro-caspase-3 to activate caspase-3, and the subsequent cleavage of the caspase substrate PARP. In the process of the induction of apoptotic cell death, Bax translocated into mitochondria, a reduction in Δψm was observed and a release of cytochrome c and apoptosis inducing factor (AIF) from mitochondria into the cytosol occurred, indicating that cell death induced by δ-elemene was through a mitochondrial-mediated pathway.
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藤原 泰之, 北川 貴大, 新開 泰弘, 鍜冶 利幸, 佐藤 雅彦2009 年 129 巻 11 号 p. 1415-1422
発行日: 2009/11/01
公開日: 2009/11/01
ジャーナル フリーMetallothionein (MT) is a cysteine-rich low molecular weight protein and thought to function in the detoxification of heavy metals and reactive oxygen species. We examined the induction of MT synthesis by cilostazol, an antiplatelet drug, in several vascular component cells to find a new pharmacological effect of cilostazol in vascular system. In human coronary artery endothelial cells, cilostazol significantly increased MT-IX and MT-IIA mRNA levels after the treatment for 6 h and endogenous MT-I/II protein levels after the treatment for 24 and 48 h. In addition, cadmium cytotoxicity was prevented by cilostazol in this endothelial cells. Moreover, cilostazol increased MT-IX and MT-IIA mRNA levels in human coronary artery smooth muscle cells, human brain microvascular endothelial cells, human brain microvascular pericytes and human colon carcinoma Caco-2 cells after the treatment for 6 h. Interestingly, cilostazol also increased MT-III mRNA level in brain microvascular endothelial cells more effectively than in other vascular cells. The present results suggest that cilostazol can protect the vascular system from toxic substances such as heavy metals via MT induction in vascular cells.
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ノート
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橋本 フミ惠, 小野 明日香, 松岡 菊美, 横田 貞記, 関 博之, 竹田 省, 林 秀徳2009 年 129 巻 11 号 p. 1423-1430
発行日: 2009/11/01
公開日: 2009/11/01
ジャーナル フリーWe studied the hormone excretion of human immortalized extravillous trophoblast cells (TCL-2, first-trimester cells) and determined whether peroxisomes are present in TCL-2. The results of TCL-2 were compared with those of TCL-1 (third-trimester cells). Morphologically, TCL-2 cells were fibroblast-like, and the growth rate of TCL-2 was slower than that of TCL-1 during 3 days culture. Progesterone was detected in the medium of TCL-2, and its concentration was approximately one-tenth of that in TCL-1. The activity of the peroxisomal marker enzyme catalase was detected in the TCL-2 homogenate, and it was about one-third the level of that in TCL-1. Fatty acyl-CoA oxidase activity was detected in TCL-2, and it was about one-seventh the level of that in TCL-1. On the other hand, human chorionic gonadotropin (hCG) was detected in the medium of TCL-2, and its concentration after 3 days of culture was about 2-fold that in TCL-1. Using the diaminobenzidine (DAB) method, peroxisomes were found in TCL-2, but only a very small amount of catalase was detected. These results indicate that human immortalized extravillous trophoblast cells (TCL-2) synthesize, secrete hCG and progesterone, and may contain peroxisomes. Because extravillous trophoblast cells are difficult to obtain from the first-trimester placenta, TCL-2 cells are useful for the study of the physiologic functions (including peroxisomal function) of first-trimester cells.
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