Taku Murata

Mie University, Tu, Mie, Japan

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Publications (45)101.08 Total impact

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    ABSTRACT: Cyclic nucleotide phosphodiesterases (PDEs) regulate the intracellular concentrations and effects of adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP). The role of PDEs in malignant tumor cells is still uncertain. The role of PDEs, especially PDE2, in human malignant melanoma PMP cell line was examined in this study. In PMP cells, 8-bromo-cAMP, a cAMP analog, inhibited cell growth and invasion. However, 8-bromo-cGMP, a cGMP analog, had little or no effect. PDE2 and PDE4, but not PDE3, were expressed in PMP cells. Growth and invasion of PMP cells were inhibited by erythro-9-(2-Hydroxy-3-nonyl) adenine (EHNA), a specific PDE2 inhibitor, but not by rolipram, a specific PDE4 inhibitor. Moreover, cell growth and invasion were inhibited by transfection of small interfering RNAs (siRNAs) specific for PDE2A and a catalytically-dead mutant of PDE2A. After treating cells with EHNA or rolipram, intracellular cAMP concentrations were increased. Growth and invasion were stimulated by PKA14-22, a PKA inhibitor, and inhibited by N(6)-benzoyl-c AMP, a PKA specific cAMP analogue, whereas 8-(4-chlorophenylthio)-2'-O-methyl-cAMP, an Epac specific cAMP analogue, did not. Invasion, but not growth, was stimulated by A-kinase anchor protein (AKAP) St-Ht31 inhibitory peptide. Based on these results, PDE2 appears to play an important role in growth and invasion of the human malignant melanoma PMP cell line. Selectively suppressing PDE2 might possibly inhibit growth and invasion of other malignant tumor cell lines.
    Cellular Signalling 04/2014; 26(9). DOI:10.1016/j.cellsig.2014.03.031 · 4.32 Impact Factor
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    ABSTRACT: The prognosis for malignant melanoma is poor; therefore, new diagnostic methods and treatment strategies are urgently needed. Phosphodiesterase 2 (PDE2) is one of 21 phosphodiesterases, which are divided into 11 families (PDE1-PDE11). PDE2 hydrolyzes cyclic AMP (cAMP) and cyclic GMP (cGMP), and its binding to cGMP enhances the hydrolysis of cAMP. We previously reported the expression of PDE1, PDE3 and PDE5 in human malignant melanoma cells. However, the expression of PDE2 in these cells has not been investigated. Herein, we examined the expression of PDE2A and its role in human oral malignant melanoma PMP cells. Sequencing of RT-PCR products revealed that PDE2A2 was the only variant expressed in PMP cells. Four point mutations were detected; one missense mutation at nucleotide position 734 (from C to T) resulted in the substitution of threonine with isoleucine at amino acid position 214. The other three were silent mutations. An in vitro migration assay and a terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay revealed that suppressing PDE2 activity with its specific inhibitor, erythro-9-(2-hydroxy-3-nonyl)-adenine (EHNA), had no impact on cell motility or apoptosis. Furthermore, the cytotoxicity of EHNA, assessed using a trypan blue exclusion assay, was negligible. On the other hand, assessment of cell proliferation by BrdU incorporation and cell cycle analysis by flow cytometry revealed that EHNA treatment inhibited DNA synthesis and increased the percentage of G2/M-arrested cells. Furthermore, cyclin A mRNA expression was downregulated, while cyclin E mRNA expression was upregulated in EHNA-treated cells. Our results demonstrated that the PDE2A2 variant carrying point mutations is expressed in PMP cells and may affect cell cycle progression by modulating cyclin A expression. Thus, PDE2A2 is a possible new molecular target for the treatment of malignant melanoma.
    Oncology Reports 01/2013; 29(4). DOI:10.3892/or.2013.2260 · 2.30 Impact Factor
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    ABSTRACT: Phosphodiesterases (PDEs) are important regulators of signal transduction processes. Eleven PDE gene families (PDE1-11) have been identified and several PDE isoforms are selectively expressed in various cell types. PDE4 family members specifically hydrolyze cyclic AMP (cAMP). Four genes (PDE4A-D) are known to encode PDE4 enzymes, with additional diversity generated by the use of alternative mRNA splicing and the use of different promoters. While PDE4 selective inhibitors show therapeutic potential for treating major diseases such as asthma and chronic obstructive pulmonary disease, little is known concerning the role of PDE4 in malignant melanoma. In this study, we examined the role of PDE4 in mouse B16-F10 melanoma cells. In these cells, PDE4 activity was found to be ∼60% of total PDE activity. RT-PCR detected only PDE4B and PDE4D mRNA. Cell growth was inhibited by the cAMP analog, 8-bromo-cAMP, but not by the specific PDE4 inhibitors, rolipram and denbufylline, which increased intracellular cAMP concentrations. Finally, migration of the B16-F10 cells was inhibited by the PDE4 inhibitors and 8-bromo-cAMP, while migration was increased by a protein kinase A (PKA) inhibitor, PKI(14-22), and was not affected by 8-pCPT-2'-O-Me-cAMP, which is an analog of exchange protein activated by cAMP (Epac). The inhibitory effect of rolipram on migration was reversed by PKI(14-22). Based on these results, PDE4 appears to play an important role in the migration of B16-F10 cells, and therefore may be a novel target for the treatment of malignant melanoma.
    Experimental and therapeutic medicine 08/2012; 4(2):205-210. DOI:10.3892/etm.2012.587 · 1.27 Impact Factor
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    ABSTRACT: Eleven phosphodiesterase (PDE) gene families (PDE1-11) have been identified, and some PDE isoforms are selectively expressed in various cell types. Previously, we reported PDE1, PDE3 and PDE4 expressions in human malignant melanoma cells. However, the expression and role of PDE5 in malignant melanoma cells is not clear. Therefore, we characterized PDE5 in human malignant melanoma MAA cells. PDE5 activity and PDE5A mRNA expression were investigated in MAA cells. The full open reading frames for human PDE5A1 were sequenced. Effects of PDE5 inhibitors on cell growth were determined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assays. PDE5 activity and PDE5A1 mRNA expression were detected in MAA cells. The nucleotide sequence of PDE5A1 was identical to that of human PDE5A1, previously published. Two PDE5 inhibitors inhibited the growth of cells. PDE5A1 mRNA is expressed and may play an important role in the growth of human malignant melanoma MAA cells.
    Anticancer research 02/2010; 30(2):355-8. · 1.83 Impact Factor
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    ABSTRACT: Cyclic adenosine 3'5'-monophosphate (cAMP) and cyclic guanosine 3'5'-monophosphate (cGMP) are critical intracellular messengers involved in transduction of signals generated by a wide variety of extracellular stimuli, including growth factors, cytokines, peptide hormones, light and neurotransmitters. These messengers modulate many fundamental biological processes, including myocardial contractility, platelet aggregation, vascular smooth muscle relaxation, proliferation and apoptosis, etc. Cyclic nucleotide phosphodiesterases (PDEs) catalyze the hydrolysis of cAMP and cGMP, and are important in regulating intracellular concentrations and biological actions of these signal-transducing molecules. These enzymes contain at least 11 highly regulated and structurally related gene families (PDE1-11). In this review, we will discuss some general information of PDEs and then focus on PDE3 gene family, including the molecular biology, structure, function and potential as therapeutic targets. Furthermore, we show the possibilities of PDE3 as therapeutic targets in malignant tumor cells and salivary gland.
    Cardiovascular & hematological agents in medicinal chemistry 08/2009; 7(3):206-11. DOI:10.2174/187152509789105453

  • International Journal of Oral and Maxillofacial Surgery 05/2009; 38(5):435-435. DOI:10.1016/j.ijom.2009.03.141 · 1.57 Impact Factor
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    ABSTRACT: Differentiation-inducing factor 1 [DIF-1; 1-(3,5-dichloro-2,6-dihydroxy-4-methoxyphenyl) hexan-1-one] from Dictyostelium discoideum exhibits antiproliferative activity in mammalian cells. We have previously shown that phosphodiesterase 1 (PDE1) is a pharmacological target of DIF-1, but there are no reports of PDE1 in human malignant melanoma cells. Therefore, we characterized PDE1 in human malignant melanoma MAA cells. PDE1 mRNA expression was investigated in MAA cells. The full open reading frames for human PDE1C1 and PDE1C3 were cloned. Cell growth was determined by MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt] assay. PDE1C mRNA expression was detected in MAA cells. The nucleotide sequence of PDE1C1 was identical to that of human PDE1C1, previously published. At nucleotide 2246 in PDE1C3, A was replaced by G, but this did not change the encoded amino acid. Cell growth was inhibited by the PDE1 inhibitor vinpocetin. PDE1C mRNA is expressed and may play an important role in human malignant melanoma MAA cells.
    Anticancer research 05/2009; 29(4):1119-22. · 1.83 Impact Factor
  • Y. Watanabe · T. Murata · K. Shimizu · K. Mizoi · J. Nomura · T. Tagawa ·

    Journal of Cranio-Maxillofacial Surgery 09/2008; 36. DOI:10.1016/S1010-5182(08)71271-X · 2.93 Impact Factor
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    ABSTRACT: Xeroderma pigmentosum is a rare, autosomal recessive genetic disease accompanied by abnormal DNA function due to damage by ultraviolet radiation. Xeroderma pigmentosum typically has general features of high light sensitivity and a high incidence of skin cancer in regions exposed to sunlight. We report the case of squamous cell carcinoma of the lower lip in an 82-year-old patient with xeroderma pigmentosum who was successfully treated with peplomycin after first receiving treatment for diabetes.
    Asian Journal of Oral and Maxillofacial Surgery 12/2007; 19(4):222-225. DOI:10.1016/S0915-6992(07)80009-4
  • K. Shimizu · T. Murata · Y. Watanabe · K. Hiramoto · M. Sekida · T. Tagawa ·

    International Journal of Oral and Maxillofacial Surgery 11/2007; 36(11):975-975. DOI:10.1016/j.ijom.2007.08.020 · 1.57 Impact Factor
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    ABSTRACT: Although placental proteins play multiple roles in fetal and placental development and in the maintenance of pregnancy, many remain inadequately characterized. In the present study, we comprehensively analyzed these proteins by using a proteomic approach. Samples were denatured with guanidine hydrochloride, which was found to be superior to the commonly used urea for the present purpose, and subjected to 2-dimensional (2D) electrophoresis (2-DE) to obtain placental proteome maps. The identified protein spots (ca. 60% of the total) on the proteome maps included several pregnancy-related proteins (PRPs). Furthermore, a novel 2D immunoblotting (2-DI) analysis of molecules related to pre-eclampsia revealed three immunopositive spots that appeared to correspond to dynactin p-50, a protein related to cell turn-over. The rate of positivity for dynactin p-50-reactive antibodies was significantly (P=0.0024) higher in 26 pre-eclamptic women than in 58 normally pregnant women. These results indicate that dynactin p-50 may be involved in the pathophysiology of pre-eclampsia.
    Placenta 08/2007; 28(7):676-87. DOI:10.1016/j.placenta.2006.10.005 · 2.71 Impact Factor

  • Journal of Oral and Maxillofacial Surgery 07/2007; 65(6):1253-5. DOI:10.1016/j.joms.2005.11.078 · 1.43 Impact Factor
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    ABSTRACT: The activity, expression and function of phosphodiesterase 4 (PDE 4) were investigated in the HMG human gingiva-derived malignant melanoma cell line. A specific PDE4 inhibitor, rolipram, inhibited PDE activity in homogenates of HMG cells, and PDE4B and 4D mRNAs were detected by RT-PCR in RNA from HMG cells. Two specific PDE4 inhibitors, rolipram and Ro-20-1724, and an adenylate cyclase activator, forskolin, increased intracellular cAMP in HMG cells. Cell growth induced by rolipram, Ro-20-1724, and forskolin was inhibited by the H-89 protein kinase A (PKA) inhibitor. However, in contrast to effects of H-89, two other PKA inhibitors, KT5720 and PKI, did not inhibit rolipram-induced cell growth. A cAMP analogue that selectively activates Epac, 8-pCPT-2'-O-Me-cAMP, also promoted the growth of HMG cells. These findings suggested that PDE4, PDE4B and/or 4D regulate cell growth through cAMP targets in the HMG malignant melanoma cell line. There have been no previous studies of positive regulation of cell growth by PDE4 inhibition, suggesting that it may be possible to target PDE4 in therapy for human malignant melanoma.
    Oncology Reports 05/2007; 17(5):1133-9. DOI:10.3892/or.17.5.1133 · 2.30 Impact Factor
  • T Sugiyama · T Nakagawa · C Sato · T Fujii · K Mine · K Shimizu · T Murata · T Tagawa ·
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    ABSTRACT: To evaluate the effects of various 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) on ectopic osteoinduction by recombinant human bone morphogenetic protein-2 (rhBMP-2) using different administration methods. Disks containing 5 mug of rhBMP-2 and type I collagen were implanted into the calf muscles of 6-week-old male rats (n = 64). Either the lactone form of simvastatin (SV), open hydroxy-acid form of simvastatin (SVA), cerivastatin (CVA), or vehicle (control) was then administered per orally (PO group) or subcutaneously (SC group) for 20 days. The disks were removed on day 21 after implantation, and ectopic induced bone formation was evaluated by radiographic, histologic, and biochemical analysis. Both the projected and radiopaque area on X-ray film, and the calcium content of the SV group in the SC group (SV-SC group) were significantly greater than those in the other SC and PO groups. Alkaline phosphatase activity and tartrate-resistant acid phosphatase activity in the SV-SC group were significantly lower than those in the other SC and PO groups. Histologic examination revealed an increase of ectopic induced bone volume in the SV-SC group. Subcutaneous administration of SV stimulates ectopic osteoinduction by rhBMP-2 through reduction of bone turnover.
    Oral Diseases 04/2007; 13(2):228-33. DOI:10.1111/j.1601-0825.2006.01271.x · 2.43 Impact Factor
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    ABSTRACT: Aim: Acromegaly is caused by excessive secretion of growth hormone (GH) usually associated with a pituitary adenoma. Acromegaly is associated with several oral complications. There are few reports of gingivitis in patients with acromegaly. This paper describes a case of intractable gingivitis in acromegaly. Materials and Methods: A 48-year-old Japanese woman was referred to our department in June 1998 complaining of gingival bleeding. The clinical diagnosis of marginal periodontitis was made. Extraction of loose teeth and scaling were performed and the patient was given brushing instructions. The gingiva of same region, however, swelled repeatedly. The patient visited the department of internal medicine for treatment of hypertension. The blood level of GH was high and a pituitary adenoma was discovered. The patient was diagnosed with a GH-producing pituitary adenoma-associated acromegaly. Administration of bromocriptine mesilate (Parlodel), a GH secretion inhibitor, was initiated. Results and Conclusions: Gingival swelling rapidly diminished and the gingival pocket was reduced. It is suggested that abnormal GH secretion should be included as a cause of intractable gingivitis.
    The Endocrinologist 12/2006; 17(1):20-22. DOI:10.1097/01.ten.0000257447.32994.da · 0.12 Impact Factor
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    ABSTRACT: Phosphodiesterase (PDE) 3 has been characterized in isolated rat submandibular acini. PDE3 activity was detected in homogenates of isolated rat submandibular acini; little or no PDE3 activity was found in ducts. About 62% of PDE3 activity in the acini was recovered in the supernatant fractions; 38% in particulate fractions. In the acini, but not ducts, PDE3A mRNA was detected by reverse transcriptase-polymerase chain reaction (RT-PCR). The PDE3-specific inhibitor, cilostamide, increased the ratio of apomucin mRNA/18s rRNA, as quantified by real-time RT-PCR. Our results indicate that PDE3A may be important in regulating cAMP pools that control acini functions.
    Archives of Oral Biology 03/2006; 51(2):83-8. DOI:10.1016/j.archoralbio.2005.06.012 · 1.74 Impact Factor
  • K. Shimizu · T. Murata · K. Hiramoto · M. Narita · M. Inui · T. Tagawa ·

    International Journal of Oral and Maxillofacial Surgery 12/2005; 34:4-4. DOI:10.1016/S0901-5027(05)80873-2 · 1.57 Impact Factor
  • K. Hiramoto · T. Murata · K. Shimizu · J. Nomura · M. Inui · T. Tagawa ·

    International Journal of Oral and Maxillofacial Surgery 01/2005; 34:5-5. DOI:10.1016/S0901-5027(05)80878-1 · 1.57 Impact Factor
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    Journal of Hard Tissue Biology 01/2005; 14(2):71-72. DOI:10.2485/jhtb.14.71 · 0.32 Impact Factor
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    ABSTRACT: We have been subculturing a human mandible-derived osteosarcoma cell line (HOSM-2) for approximately 15 years, and have compared the characters of early generations, which did not exhibit tumorigenicity, to those in the later generations. The shape and doubling time of the cells did not change during long-term culture. The number of chromosomes, however, changed from 59-81 in the 6th generation (modal number: 70) to 54-59 (modal number: 56 and 57), and the chromosomal structure also changed. In addition, the cell line in the later generations showed tumorigenicity in nude mice, and Codon 306 of the p53 gene was mutated to a stop codon due to a point mutation. HOSM-2 cells expressed osteoblast markers, thus confirming them to be osteoblastic osteosarcoma cells. These results showed that changes in certain genes in the HOSM-2 cells led to tumorigenicity in nude mice following long-term culture. In addition, as a mandible-derived cell line with characteristics different from those of limb-derived osteosarcoma cell lines, HOSM-2 cells may be a valuable model for mandibular osteosarcoma and osteoblasts.
    Oral Oncology 09/2004; 40(7):742-50. DOI:10.1016/j.oraloncology.2004.01.015 · 3.61 Impact Factor

Publication Stats

657 Citations
101.08 Total Impact Points


  • 1997-2013
    • Mie University
      • Department of Oral and Maxillofacial Surgery
      Tu, Mie, Japan
  • 2007
    • Nippon Medical School
      • Department of Obstetrics and Gynecology
      Edo, Tōkyō, Japan
  • 1996-2001
    • Center For Oral & Maxillofacial Surgery
      Georgia, United States
  • 2000
    • National Institutes of Health
      베서스다, Maryland, United States