Biomedical Research-tokyo最新文献_第2页

Mitochondrial DNA copy number variations in Epstein-Barr virus-transformed B cells after exposure to radiation: A possible biomarker for dose assessment. Epstein-Barr病毒转化的B细胞暴露于辐射后的线粒体DNA拷贝数变化：剂量评估的可能生物标志物。

IF 1.3 4区医学

Biomedical Research-tokyo Pub Date : 2025-01-01 DOI: 10.2220/biomedres.46.9

Hitomi Muramatsu, Ryosuke Seino, Hisanori Fukunaga

引用次数: 0

Mycophenolate mofetil reduces cell viability associated with the miR-205-PAX9 pathway in human lip fibroblast cells. 霉酚酸酯降低人唇成纤维细胞中与miR-205-PAX9通路相关的细胞活力。

IF 1.3 4区医学

Biomedical Research-tokyo Pub Date : 2025-01-01 DOI: 10.2220/biomedres.46.1

Hiroki Yoshioka, Hanane Horita, Yosuke Tsukiboshi, Hisaka Kurita, Yurie Mikami, Kenichi Ogata, Aya Ogata

{"title":"Mycophenolate mofetil reduces cell viability associated with the miR-205-PAX9 pathway in human lip fibroblast cells.","authors":"Hiroki Yoshioka, Hanane Horita, Yosuke Tsukiboshi, Hisaka Kurita, Yurie Mikami, Kenichi Ogata, Aya Ogata","doi":"10.2220/biomedres.46.1","DOIUrl":"10.2220/biomedres.46.1","url":null,"abstract":"Cleft lip is a birth defect associated with environmental and genetic factors. Recently, microRNAs (miRNAs) have been reported to play a crucial role in lip formation, with the disruption of miRNAs influencing the development of cleft lip. Exposure to medicinal agents in pregnant women is one of the reasons for cleft lip. Although an association between pharmaceuticals-induced cleft lip and miRNAs has been suggested, it remains to be fully elucidated. This study aimed to clarify the molecular mechanism of mycophenolate mofetil (MPM)-induced inhibition of cell proliferation and miRNA expression in human lip fibroblast (KD) cells. Cell viability, apoptosis, and cell cycle-related markers were evaluated after 72 h of MPM treatment. In addition, miRNA levels and the expression of their downstream genes were measured, and a rescue experiment was performed by overexpressing PAX9. We showed that MPM dose-dependently reduced the viability of KD cells. In addition, MPM treatment suppressed cyclin-D1 and cyclin dependent kinase-6 expression in KD cells. Furthermore, MPM upregulated miR-205 expression and downregulated the expression of PAX9 (downstream gene). Moreover, PAX9 overexpression alleviated MPM-induced inhibition of cell proliferation. These results suggest that MPM suppresses cell viability by modulating miR-205-PAX9 expression.","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":"46 1","pages":"1-8"},"PeriodicalIF":1.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bone regeneration-enhancing effects of extremely low-frequency electromag- netic fields: Analysis using fish scales as a bone model. 极低频电场对骨骼再生的促进作用：以鱼鳞为骨骼模型的分析。

IF 1.3 4区医学

Biomedical Research-tokyo Pub Date : 2024-01-01 DOI: 10.2220/biomedres.45.187

Nobuo Suzuki, Makiko Kakikawa, Yuta Oda, Jingjing Kobayashi-Sun, Sotoshi Yamada, Kouhei Kuroda, Isao Kobayashi, Masato Honda, Hajime Matsubara, Yoshiaki Tabuchi, Nobuaki Shimizu, Kazuki Watanabe, Jun Hirayama, Atsuhiko Hattori

{"title":"Bone regeneration-enhancing effects of extremely low-frequency electromag- netic fields: Analysis using fish scales as a bone model.","authors":"Nobuo Suzuki, Makiko Kakikawa, Yuta Oda, Jingjing Kobayashi-Sun, Sotoshi Yamada, Kouhei Kuroda, Isao Kobayashi, Masato Honda, Hajime Matsubara, Yoshiaki Tabuchi, Nobuaki Shimizu, Kazuki Watanabe, Jun Hirayama, Atsuhiko Hattori","doi":"10.2220/biomedres.45.187","DOIUrl":"https://doi.org/10.2220/biomedres.45.187","url":null,"abstract":"Electromagnetic fields (EMFs) noninvasively promote fracture healing, prevent osteoporosis, promote diaphyseal growth, enhance differentiation, and stimulate cell division. However, no good model systems for analyzing bone regeneration have been reported. In this study, we examined the in vivo regeneration of scales having osteoblasts and osteoclasts using a new magnetic field generator for exposing aquatic animals to EMFs at a sine-wave frequency of 60 Hz. Goldfish scales were put into a fish-breeding space with the developed magnetic field generator and exposed to extremely low-frequency electromagnetic fields (ELF-EMFs) of 60 Hz at an intensity of 1, 3, and 5 mT for 10 days while being regenerated the scales. After exposure, alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) activities in the goldfish scales were measured as markers of osteoblasts and osteoclasts, respectively. As a result, both ALP and TRAP activities in regenerating scales exposed to 3 mT ELF-EMFs were higher than those in regenerating scales exposed to 1 and 5 mT ELF-EMFs. Exposure of scales to 3 mT ELF-EMFs significantly enhanced the scale regeneration rate. Exposure of rat calvaria to 3 mT ELF-EMFs also increased both ALP and TRAP activities like in goldfish scales. Thus, we concluded that 3 mT ELF-EMFs contribute to the medical treatment of bone diseases.","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":"45 5","pages":"187-195"},"PeriodicalIF":1.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of membrane proteins targeted by small-molecule compounds using nanomagnetic beads. 利用纳米磁珠鉴定小分子化合物靶向的膜蛋白。

IF 1.3 4区医学

Biomedical Research-tokyo Pub Date : 2024-01-01 DOI: 10.2220/biomedres.45.179

Yasufumi Kikuchi, Takayuki Ando, Tadashi Ashizawa, Akira Iizuka, Akari Kanematsu, Chie Maeda, Chikako Hozumi, Haruo Miyata, Kazue Yamashita, Tomoatsu Ikeya, Ken Yamaguchi, Yasuto Akiyama

{"title":"Identification of membrane proteins targeted by small-molecule compounds using nanomagnetic beads.","authors":"Yasufumi Kikuchi, Takayuki Ando, Tadashi Ashizawa, Akira Iizuka, Akari Kanematsu, Chie Maeda, Chikako Hozumi, Haruo Miyata, Kazue Yamashita, Tomoatsu Ikeya, Ken Yamaguchi, Yasuto Akiyama","doi":"10.2220/biomedres.45.179","DOIUrl":"https://doi.org/10.2220/biomedres.45.179","url":null,"abstract":"In drug discovery research, it is important to identify target proteins of bioactive small-molecule compounds and analyse their functions. In this study, we examined whether target membrane proteins could be captured by compounds that bind to membrane proteins on the cell surface. For this purpose, we performed affinity purification using the compound-immobilized nanomagnetic beads. Affinity purification with nanomagnetic beads is known to be effective for determining the protein binding partners of small molecules. However, most previous studies have targeted proteins in the cytoplasm. As a model compound, we chose BMS-1166 (a representative small-molecule compound from Bristol Myers Squibb), a PD-1/PD-L1 immune checkpoint inhibitor that binds to PD- L1 and promotes PD-L1 dimerization. BMS-1166-immobilized beads were manufactured and incubated with extracts of cells with high PD-L1 protein expression. The bound protein was confirmed by western blotting and proteomic analysis to be PD-L1. BMS-1166-immobilized nano-magnetic beads were able to specifically bind and capture the membrane protein PD-L1. In addition, high-purity protein could be obtained from cell extracts in a single step. This is the first report of the purification of a membrane protein to high purity with nanobeads. Nanomagnetic beads with immobilized compounds are an effective tool for identifying the protein binding partners of small molecules, especially when the targets are membrane proteins.","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":"45 5","pages":"179-186"},"PeriodicalIF":1.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Calcium phosphate controls nucleation and growth of calcium oxalate crystal phases in kidney stones. 磷酸钙控制着肾结石中草酸钙晶相的成核和生长。

IF 1.2 4区医学

Biomedical Research-tokyo Pub Date : 2024-01-01 DOI: 10.2220/biomedres.45.103

Uta Michibata, Mihoko Maruyama, Yutaro Tanaka, Masashi Yoshimura, Hiroshi Yoshikawa, Kazufumi Takano, Yoshihiro Furukawa, Koichi Momma, Rie Tajiri, Kazumi Taguchi, Shuzo Hamamoto, Atsushi Okada, Kenjiro Kohri, Takahiro Yasui, Shigeyoshi Usami, Masashi Imanishi, Yusuke Mori

{"title":"Calcium phosphate controls nucleation and growth of calcium oxalate crystal phases in kidney stones.","authors":"Uta Michibata, Mihoko Maruyama, Yutaro Tanaka, Masashi Yoshimura, Hiroshi Yoshikawa, Kazufumi Takano, Yoshihiro Furukawa, Koichi Momma, Rie Tajiri, Kazumi Taguchi, Shuzo Hamamoto, Atsushi Okada, Kenjiro Kohri, Takahiro Yasui, Shigeyoshi Usami, Masashi Imanishi, Yusuke Mori","doi":"10.2220/biomedres.45.103","DOIUrl":"https://doi.org/10.2220/biomedres.45.103","url":null,"abstract":"Kidney stone disease is a serious disease due to the severe pain it causes, high morbidity, and high recurrence rate. Notably, calcium oxalate stones are the most common type of kidney stone. Calcium oxalate appears in two forms in kidney stones: the stable phase, monohydrate (COM), and the metastable phase, dihydrate (COD). Particularly, COM stones with concentric structures are hard and difficult to treat. However, the factor determining the growth of either COM or COD crystals in the urine, which is supersaturated for both phases, remains unclear. This study shows that calcium phosphate ingredients preferentially induce COM crystal nucleation and growth, by observing and analyzing kidney stones containing both COM and COD crystals. The forms of calcium phosphate are not limited to Randall's plaques (1-2 mm size aggregates, which contain calcium phosphate nanoparticles and proteins, and form in the renal papilla). For example, aggregates of strip-shaped calcium phosphate crystals and fields of dispersed calcium phosphate microcrystals (nano to micrometer order) also promote the growth of concentric COM structures. This suggests that patients who excrete urine with a higher quantity of calcium phosphate crystals may be more prone to forming hard and troublesome COM stones.","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":"45 3","pages":"103-113"},"PeriodicalIF":1.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141261429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Copper-induced renal toxicity controlled by period1 through modulation of Atox1 in mice. 铜诱导的小鼠肾毒性通过调节 Atox1 受 period1 控制。

IF 1.3 4区医学

Biomedical Research-tokyo Pub Date : 2024-01-01 DOI: 10.2220/biomedres.45.143

Sarah Tominaga, Hiroki Yoshioka, Satoshi Yokota, Yosuke Tsukiboshi, Masumi Suzui, Makoto Nagai, Hirokazu Hara, Nobuhiko Miura, Tohru Maeda

{"title":"Copper-induced renal toxicity controlled by period1 through modulation of Atox1 in mice.","authors":"Sarah Tominaga, Hiroki Yoshioka, Satoshi Yokota, Yosuke Tsukiboshi, Masumi Suzui, Makoto Nagai, Hirokazu Hara, Nobuhiko Miura, Tohru Maeda","doi":"10.2220/biomedres.45.143","DOIUrl":"10.2220/biomedres.45.143","url":null,"abstract":"Copper (Cu) is known to induce oxidative stress and apoptosis in the liver, kidney, and brain. We previously demonstrated the molecular mechanism underlying the Cu-induced hepatic diurnal variation. However, the cellular molecule(s) involved in Cu-induced renal chronotoxicity remain unknown. In this study, we aimed to elucidate the molecular mechanisms underlying Cu-induced diurnal toxicity in the kidneys. We evaluated cell viability and clock gene expression levels in mouse renal cortex tubular cells (MuRTE61 cells) after Cu treatment. We also examined the Cu homeostasis- and apoptosis-related gene levels after period 1 (Per1) overexpression in MuRTE61 cells. Cu treatment decreased MuRTE61 cell viability in a dose-dependent manner. It increased the Per1 expression levels after 24 h. Notably, Per1 overexpression alleviated the Cu-induced inhibition of MuRTE61 cell viability. Moreover, Per1 overexpression downregulated the cleaved caspase-3 and reduced Cu levels by upregulating the antioxidant 1 copper chaperone (Atox1) levels. These results suggest that Cu-induced renal toxicity is associated with Per1 expression via the regulation of the copper chaperone, Atox1.","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":"45 4","pages":"143-149"},"PeriodicalIF":1.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effects of linalool on respiratory neuron activity in the brainstem-spinal cord preparation from newborn rats. 芳樟醇对新生大鼠脑干脊髓制备物中呼吸神经元活动的影响

IF 1.3 4区医学

Biomedical Research-tokyo Pub Date : 2024-01-01 DOI: 10.2220/biomedres.45.151

Yuka Shibuya, Kayo Tsuzawa, Hiroshi Onimaru, Masahiko Izumizaki

{"title":"Effects of linalool on respiratory neuron activity in the brainstem-spinal cord preparation from newborn rats.","authors":"Yuka Shibuya, Kayo Tsuzawa, Hiroshi Onimaru, Masahiko Izumizaki","doi":"10.2220/biomedres.45.151","DOIUrl":"https://doi.org/10.2220/biomedres.45.151","url":null,"abstract":"Linalool and linalyl acetate are major components of lavender essential oil. These substances possess many biological activities, such as anti-inflammatory activity, analgesic and anxiolytic effects, and anticonvulsant properties, and they also induce modulation of neuronal activity in the autonomic nervous system. However, there are no reports of the direct effects of linalool on respiratory activity. In the present study, we analyzed the effects of linalool and linalyl acetate on central respiratory activity in the brainstem-spinal cord preparation isolated from newborn rats. Linalool dose-dependently decreased the rate of respiratory activity. This effect was reversed by bicuculline, suggesting that linalool enhanced inhibitory synaptic connections via GABAA receptors. In addition, linalool reduced the coefficient of variation of inspiratory burst intervals and thus could work to stabilize the respiratory rhythm. Linalyl acetate did not cause inhibitory effects as observed in linalool treatment. Linalool depressed burst activity of pre-inspiratory neurons in the medullary respiratory networks and increased the amplitude of inspiratory inhibitory postsynaptic potentials of pre-inspiratory neurons. We concluded that linalool caused inhibitory effects on respiratory rhythm generation mainly through activation of presynaptic GABAA receptors of pre-inspiratory neurons.","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":"45 4","pages":"151-161"},"PeriodicalIF":1.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Blockade of CD80/CD86-CD28 co-stimulation augments the inhibitory function of peptide antigen-specific regulatory T cells. 阻断 CD80/CD86-CD28 协同刺激可增强肽抗原特异性调节性 T 细胞的抑制功能。

IF 1.2 4区医学

Biomedical Research-tokyo Pub Date : 2024-01-01 DOI: 10.2220/biomedres.45.115

Yui Maehara, Kazuyoshi Takeda, Kyoko Tsuji-Yogo, Kodai Morimoto, Masaki Harada, Kyohei Kuriyama, Saori Hirota, Hideo Yagita, Ko Okumura, Koichiro Uchida

{"title":"Blockade of CD80/CD86-CD28 co-stimulation augments the inhibitory function of peptide antigen-specific regulatory T cells.","authors":"Yui Maehara, Kazuyoshi Takeda, Kyoko Tsuji-Yogo, Kodai Morimoto, Masaki Harada, Kyohei Kuriyama, Saori Hirota, Hideo Yagita, Ko Okumura, Koichiro Uchida","doi":"10.2220/biomedres.45.115","DOIUrl":"10.2220/biomedres.45.115","url":null,"abstract":"Mixed lymphocyte culture under the blockade of CD80/CD86-CD28 co-stimulation induces anergic (completely hyporesponsive) T cells with immune suppressive function (inducible suppressing T cells: iTS cells). Previously, iTS cell therapy has demonstrated outstanding benefits in clinical trials for organ transplantation. Here, we examined whether peptide antigen-specific iTS cells are inducible. DO 11.10 iTS cells were obtained from splenocytes of BALB/c DO 11.10 mice by stimulation with OVA peptide and antagonistic anti-CD80/CD86 mAbs. When DO 11.10 iTS or Foxp3- DO 11.10 iTS cells were stimulated with OVA, these cells produced IL-13, but not IL-4. DO 11.10 iTS cells decreased IL-4 and increased IL-13 production from OVA-stimulated naïve DO 11.10 splenocytes. When Foxp3+ DO 11.10 iTS cells were prepared, these cells significantly inhibited the production of IL-4 and IL-13 compared with freshly isolated Foxp3+ DO 11.10 T cells. Moreover, an increase in the population expressing OX40, ICOS, and 4-1BB suggested activation of Foxp3+ DO 11.10 iTS cells. Thus, blockade of CD80/CD86-CD28 co-stimulation during peptide antigen stimulation augments the inhibitory function of Foxp3+ regulatory T cells, and does not induce anergic Foxp3- conventional T cells. Peptide-specific Foxp3+ regulatory iTS cells could be useful for the treatment of allergic and autoimmune diseases without adverse effects.","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":"45 3","pages":"115-123"},"PeriodicalIF":1.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141261390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Analgesic effects of linalyl acetate via nociceptive TRPV1 inhibition in mice. 乙酸芳樟酯通过抑制小鼠痛觉 TRPV1 产生镇痛效果。

IF 1.3 4区医学

Biomedical Research-tokyo Pub Date : 2024-01-01 DOI: 10.2220/biomedres.45.217

Miho Hashimoto, Kenji Takahashi, Toshio Ohta

{"title":"Analgesic effects of linalyl acetate via nociceptive TRPV1 inhibition in mice.","authors":"Miho Hashimoto, Kenji Takahashi, Toshio Ohta","doi":"10.2220/biomedres.45.217","DOIUrl":"https://doi.org/10.2220/biomedres.45.217","url":null,"abstract":"Transient receptor potential vanilloid 1 (TRPV1) is primarily expressed in sensory neurons and functions as a nociceptive channel. TRPV1 is activated by capsaicin, acidic pH, and noxious heat. Compounds inhibiting TRPV1 have been explored to develop analgesic drugs. In this study, the effect of linalyl acetate (LA), a lavender essential oil component that exerts analgesic effects, on TRPV1 was investigated by measuring intracellular Ca2+ concentration ([Ca2+]i) and whole-cell membrane currents. The analgesic effects of LA on TRPV1-mediated pain were also examined. LA inhibited [Ca2+]i responses to capsaicin, acidic pH, and heat in mouse sensory neurons. Unlike the transient LA-inhibition on capsaicin- and heat-responses, its inhibition on acid-responses persisted even after the LA removal. In TRPV1-expressing HEK293 cells, LA reversibly suppressed [Ca2+]i responses to capsaicin and heat, but persistently inhibited those to acids. Similarly, LA reversibly attenuated current responses to capsaicin but durably suppressed those to acids. LA sustainingly inhibited the responses to spermine, an endogenous TRPV1 agonist, and reduced pain-related behaviors induced by spermine and noxious heat. These results indicate that LA inhibits TRPV1 in a mode-independent manner, with long-lasting inhibition of acid-induced TRPV1 activation. These inhibitory actions of LA on TRPV1 may be related to its analgesic effects.","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":"45 6","pages":"217-230"},"PeriodicalIF":1.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142708944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Serotonin reuptake inhibitor suppresses the activation of human platelets by a combination of thrombopoietin and collagen through inhibition of Rac and Rho/Rho-kinase. 血清素再摄取抑制剂通过抑制 Rac 和 Rho/Rho-激酶，抑制血小板在血小板生成素和胶原蛋白联合作用下的活化。

IF 1.3 4区医学

Biomedical Research-tokyo Pub Date : 2024-01-01 DOI: 10.2220/biomedres.45.231

Haruhiko Tokuda, Takamitsu Hori, Takashi Onuma, Yukiko Enomoto, Tomoaki Doi, Rie Matsushima-Nishiwaki, Shinobu Yamaguchi, Kumiko Tanabe, Takuya Omura, Shinji Ogura, Toru Iwama, Hiroki Iida, Osamu Kozawa

{"title":"Serotonin reuptake inhibitor suppresses the activation of human platelets by a combination of thrombopoietin and collagen through inhibition of Rac and Rho/Rho-kinase.","authors":"Haruhiko Tokuda, Takamitsu Hori, Takashi Onuma, Yukiko Enomoto, Tomoaki Doi, Rie Matsushima-Nishiwaki, Shinobu Yamaguchi, Kumiko Tanabe, Takuya Omura, Shinji Ogura, Toru Iwama, Hiroki Iida, Osamu Kozawa","doi":"10.2220/biomedres.45.231","DOIUrl":"https://doi.org/10.2220/biomedres.45.231","url":null,"abstract":"Tramadol and duloxetine, reuptake inhibitors of serotonin and noradrenaline, are widely used analgesics. Cytoplasmic serotonin in human platelets reportedly regulates the activity of low-molecular-weight GTP-binding proteins via serotonylation, leading to the modulation of platelet functions. We recently showed that the combination of thrombopoietin and collagen in the low doses synergistically induces human platelet activation via Rac and Rho/Rho-kinase. In the present study, we investigated the effects of tramadol and duloxetine on the synergistic effect, and the mechanism. Tramadol reduced the platelet aggregation and the release of PDGF-AB by the combination of thrombopoietin and collagen in the low doses. The aggregation and the release were also inhibited by duloxetine. Not reboxetine, a specific inhibitor of noradrenaline transporter, but fluvoxamine and sertraline, specific inhibitors of serotonin transporter suppressed the aggregation and the release. Tramadol, duloxetine, fluvoxamine and sertraline but not reboxetine attenuated the levels of GTP-Rac and GTP-Rho, and phospho-cofilin induced by the combination. Taken together, our results strongly suggest that tramadol and duloxetine, not as noradrenaline reuptake inhibitor but as serotonin reuptake inhibitor, suppress the activation of Rac and Rho/Rho-kinase elicited by the combination of subthreshold thrombopoietin and collagen, leading to the attenuation of human platelet activation.","PeriodicalId":9138,"journal":{"name":"Biomedical Research-tokyo","volume":"45 6","pages":"231-241"},"PeriodicalIF":1.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142708929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0