Journal of pharmacological sciences最新文献

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Sulfide and polysulfide as pronociceptive mediators: Focus on Cav3.2 function enhancement and TRPA1 activation 硫化物和多硫化物作为前感觉介质:关注 Cav3.2 功能增强和 TRPA1 激活
IF 3.5 3区 医学
Journal of pharmacological sciences Pub Date : 2024-05-03 DOI: 10.1016/j.jphs.2024.04.007
Fumiko Sekiguchi, Maho Tsubota, Atsufumi Kawabata
{"title":"Sulfide and polysulfide as pronociceptive mediators: Focus on Cav3.2 function enhancement and TRPA1 activation","authors":"Fumiko Sekiguchi,&nbsp;Maho Tsubota,&nbsp;Atsufumi Kawabata","doi":"10.1016/j.jphs.2024.04.007","DOIUrl":"https://doi.org/10.1016/j.jphs.2024.04.007","url":null,"abstract":"<div><p>Reactive sulfur species including sulfides, polysulfides and cysteine hydropersulfide play extensive roles in health and disease, which involve modification of protein functions through the interaction with metals bound to the proteins, cleavage of cysteine disulfide (S–S) bonds and S-persulfidation of cysteine residues. Sulfides over a wide micromolar concentration range enhance the activity of Ca<sub>v</sub>3.2 T-type Ca<sup>2+</sup> channels by eliminating Zn<sup>2+</sup> bound to the channels, thereby promoting somatic and visceral pain. Ca<sub>v</sub>3.2 is under inhibition by Zn<sup>2+</sup> in physiological conditions, so that sulfides function to reboot Ca<sub>v</sub>3.2 from Zn<sup>2+</sup> inhibition and increase the excitability of nociceptors. On the other hand, polysulfides generated from sulfides activate TRPA1 channels via cysteine S-persulfidation, thereby facilitating somatic, but not visceral, pain. Thus, Ca<sub>v</sub>3.2 function enhancement by sulfides and TRPA1 activation by polysulfides, synergistically accelerate somatic pain signals. The increased activity of the sulfide/Ca<sub>v</sub>3.2 system, in particular, appears to have a great impact on pathological pain, and may thus serve as a therapeutic target for treatment of neuropathic and inflammatory pain including visceral pain.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"155 3","pages":"Pages 113-120"},"PeriodicalIF":3.5,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000379/pdfft?md5=1f97a5fce3fdafab5cd2ab4a64c8edd8&pid=1-s2.0-S1347861324000379-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140894485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Sulfur metabolism as a new therapeutic target of heart failure 硫代谢是治疗心力衰竭的新靶点
IF 3.5 3区 医学
Journal of pharmacological sciences Pub Date : 2024-04-23 DOI: 10.1016/j.jphs.2024.04.005
Akiyuki Nishimura , Xiaokang Tang , Liuchenzi Zhou , Tomoya Ito , Yuri Kato , Motohiro Nishida
{"title":"Sulfur metabolism as a new therapeutic target of heart failure","authors":"Akiyuki Nishimura ,&nbsp;Xiaokang Tang ,&nbsp;Liuchenzi Zhou ,&nbsp;Tomoya Ito ,&nbsp;Yuri Kato ,&nbsp;Motohiro Nishida","doi":"10.1016/j.jphs.2024.04.005","DOIUrl":"https://doi.org/10.1016/j.jphs.2024.04.005","url":null,"abstract":"<div><p>Sulfur-based redox signaling has long attracted attention as critical mechanisms underlying the development of cardiac diseases and resultant heart failure. Especially, post-translational modifications of cysteine (Cys) thiols in proteins mediate oxidative stress-dependent cardiac remodeling including myocardial hypertrophy, senescence, and interstitial fibrosis. However, we recently revealed the existence of Cys persulfides and Cys polysulfides in cells and tissues, which show higher redox activities than Cys and substantially contribute to redox signaling and energy metabolism. We have established simple evaluation methods that can detect polysulfides in proteins and inorganic polysulfides in cells and revealed that polysulfides abundantly expressed in normal hearts are dramatically catabolized by exposure to ischemic/hypoxic and environmental electrophilic stress, which causes vulnerability of the heart to mechanical load. Accumulation of hydrogen sulfide, a nucleophilic catabolite of persulfides/polysulfides, may lead to reductive stress in ischemic hearts, and perturbation of polysulfide catabolism can improve chronic heart failure after myocardial infarction in mice. This review focuses on the (patho)physiological role of sulfur metabolism in hearts, and proposes that sulfur catabolism during ischemic/hypoxic stress has great potential as a new therapeutic strategy for the treatment of ischemic heart failure.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"155 3","pages":"Pages 75-83"},"PeriodicalIF":3.5,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000355/pdfft?md5=8a619fee26fd3f1f2ce79790048591f4&pid=1-s2.0-S1347861324000355-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140647141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effect of anti-claudin 18.2 monoclonal antibody zolbetuximab alone or combined with chemotherapy or programmed cell death-1 blockade in syngeneic and xenograft gastric cancer models 抗克劳丁 18.2 单克隆抗体唑贝妥昔单抗(zolbetuximab)单独或与化疗或程序性细胞死亡-1 阻断剂联合使用对合成和异种移植胃癌模型的影响
IF 3.5 3区 医学
Journal of pharmacological sciences Pub Date : 2024-04-18 DOI: 10.1016/j.jphs.2024.04.004
Toshihide Nishibata , Jane Weng , Keisuke Omori , Yuji Sato , Taisuke Nakazawa , Tomoyuki Suzuki , Tomohiro Yamada , Ikumi Nakajo , Fumitaka Kinugasa , Özlem Türeci , Uğur Şahin , Taku Yoshida
{"title":"Effect of anti-claudin 18.2 monoclonal antibody zolbetuximab alone or combined with chemotherapy or programmed cell death-1 blockade in syngeneic and xenograft gastric cancer models","authors":"Toshihide Nishibata ,&nbsp;Jane Weng ,&nbsp;Keisuke Omori ,&nbsp;Yuji Sato ,&nbsp;Taisuke Nakazawa ,&nbsp;Tomoyuki Suzuki ,&nbsp;Tomohiro Yamada ,&nbsp;Ikumi Nakajo ,&nbsp;Fumitaka Kinugasa ,&nbsp;Özlem Türeci ,&nbsp;Uğur Şahin ,&nbsp;Taku Yoshida","doi":"10.1016/j.jphs.2024.04.004","DOIUrl":"https://doi.org/10.1016/j.jphs.2024.04.004","url":null,"abstract":"<div><p>The development of targeted cancer therapies based on monoclonal antibodies against tumor-associated antigens has progressed markedly over recent decades. This approach is dependent on the identification of tumor-specific, normal tissue-sparing antigenic targets. The transmembrane protein claudin-18 splice variant 2 (CLDN18.2) is frequently and preferentially displayed on the surface of primary gastric adenocarcinomas, making it a promising monoclonal antibody target. Phase 3 studies of zolbetuximab, a chimeric immunoglobulin G1 monoclonal antibody targeting CLDN18.2, combined with 5-fluorouracil/leucovorin plus oxaliplatin (modified FOLFOX6) or capecitabine plus oxaliplatin (CAPOX) in advanced or metastatic first-line gastric or gastroesophageal junction (G/GEJ) adenocarcinoma have demonstrated favorable clinical results with zolbetuximab. In studies using xenograft or syngeneic models with gastric cancer cell lines, zolbetuximab mediated death of CLDN18.2-positive human cancer cell lines via antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity in vitro and demonstrated anti-tumor efficacy as monotherapy and combined with chemotherapy in vivo. Mice treated with zolbetuximab plus chemotherapy displayed a significantly higher frequency of tumor-infiltrating CD8<sup>+</sup> T cells versus vehicle/isotype control-treated mice. Furthermore, zolbetuximab combined with an anti-mouse programmed cell death-1 antibody more potently inhibited tumor growth compared with either agent alone. These results support the potential of zolbetuximab as a novel treatment option for G/GEJ adenocarcinoma.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"155 3","pages":"Pages 84-93"},"PeriodicalIF":3.5,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000343/pdfft?md5=9aa4b7ac0f325f5b18aeb040a6b66732&pid=1-s2.0-S1347861324000343-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140650611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Deficiency of interleukin-19 exacerbates acute lung injury induced by intratracheal treatment of hydrochloric acid 白细胞介素-19 的缺乏会加重气管内盐酸治疗引起的急性肺损伤
IF 3.5 3区 医学
Journal of pharmacological sciences Pub Date : 2024-04-17 DOI: 10.1016/j.jphs.2024.04.003
Kazuhiro Nishiyama , Joji Horikoshi , Toko Maehara , Miyuu Tanaka , Takashi Tanida , Koichi Kawada , Susumu Takeshita , Naoshige Ono , Takeshi Izawa , Mitsuru Kuwamura , Yasu-Taka Azuma
{"title":"Deficiency of interleukin-19 exacerbates acute lung injury induced by intratracheal treatment of hydrochloric acid","authors":"Kazuhiro Nishiyama ,&nbsp;Joji Horikoshi ,&nbsp;Toko Maehara ,&nbsp;Miyuu Tanaka ,&nbsp;Takashi Tanida ,&nbsp;Koichi Kawada ,&nbsp;Susumu Takeshita ,&nbsp;Naoshige Ono ,&nbsp;Takeshi Izawa ,&nbsp;Mitsuru Kuwamura ,&nbsp;Yasu-Taka Azuma","doi":"10.1016/j.jphs.2024.04.003","DOIUrl":"10.1016/j.jphs.2024.04.003","url":null,"abstract":"<div><p>Interleukin (IL-19) belongs to the IL-10 family of cytokines and plays diverse roles in inflammation, cell development, viral responses, and lipid metabolism. Acute lung injury (ALI) is a severe respiratory condition associated with various diseases, including severe pneumonia, sepsis, and trauma, lacking established treatments. However, the role of IL-19 in acute inflammation of the lungs is unknown. We reported the impact of IL-19 functional deficiency in mice crossed with an ALI model using HCl. Lungs damages, neutrophil infiltration, and pulmonary edema induced by HCl were significantly worse in IL-19 knockout (KO) mice than in wild-type (WT) mice. mRNA expression levels of C-X-C motif chemokine ligand 1 (CXCL1) and IL-6 in the lungs were significantly higher in IL-19 KO mice than in WT mice. Little apoptosis was detected in lung injury in WT mice, whereas apoptosis was observed in exacerbated area of lung injury in IL-19 KO mice. These results are the first to show that IL-19 is involved in acute inflammation of the lungs, suggesting a novel molecular mechanism in acute respiratory failures. If it can be shown that neutrophils have IL-19 receptors and that IL-19 acts directly on them, it would be a novel drug target.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"155 3","pages":"Pages 94-100"},"PeriodicalIF":3.5,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000331/pdfft?md5=1f87f3b3dbcba4297e1f78504d8e39d5&pid=1-s2.0-S1347861324000331-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140787739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Actions of remimazolam on inhibitory transmission of rat spinal dorsal horn neurons 雷马唑仑对大鼠脊髓背角神经元抑制性传导的作用
IF 3.5 3区 医学
Journal of pharmacological sciences Pub Date : 2024-04-10 DOI: 10.1016/j.jphs.2024.04.002
Rintaro Hoshino , Nobuko Ohashi , Daisuke Uta , Masayuki Ohashi , Hiroyuki Deguchi , Hiroshi Baba
{"title":"Actions of remimazolam on inhibitory transmission of rat spinal dorsal horn neurons","authors":"Rintaro Hoshino ,&nbsp;Nobuko Ohashi ,&nbsp;Daisuke Uta ,&nbsp;Masayuki Ohashi ,&nbsp;Hiroyuki Deguchi ,&nbsp;Hiroshi Baba","doi":"10.1016/j.jphs.2024.04.002","DOIUrl":"https://doi.org/10.1016/j.jphs.2024.04.002","url":null,"abstract":"<div><p>Remimazolam is an ultra-short benzodiazepine that acts on the benzodiazepine site of γ-aminobutyric acid (GABA) receptors in the brain and induces sedation. Although GABA receptors are found localized in the spinal dorsal horn, no previous studies have reported the analgesic effects or investigated the cellular mechanisms of remimazolam on the spinal dorsal horn. Behavioral measures, immunohistochemistry, and <em>in vitro</em> whole-cell patch-clamp recordings of dorsal horn neurons were used to assess synaptic transmission. Intrathecal injection of remimazolam induced behavioral analgesia in inflammatory pain-induced mechanical allodynia (six rats/dose; p &lt; 0.05). Immunohistochemical staining revealed that remimazolam suppressed spinal phosphorylated extracellular signal-regulated kinase activation (five rats/group, p &lt; 0.05). <em>In vitro</em> whole-cell patch-clamp analysis demonstrated that remimazolam increased the frequency of GABAergic miniature inhibitory post-synaptic currents, prolonged the decay time (six rats; p &lt; 0.05), and enhanced GABA currents induced by exogenous GABA (seven rats; p &lt; 0.01). However, remimazolam did not affect miniature excitatory post-synaptic currents or amplitude of monosynaptic excitatory post-synaptic currents evoked by Aδ- and C-fiber stimulation (seven rats; p &gt; 0.05). This study suggests that remimazolam induces analgesia by enhancing GABAergic inhibitory transmission in the spinal dorsal horn, suggesting its potential utility as a spinal analgesic for inflammatory pain.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"155 2","pages":"Pages 63-73"},"PeriodicalIF":3.5,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S134786132400032X/pdfft?md5=e9004f36617bcf5850b5b4c08db4c556&pid=1-s2.0-S134786132400032X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140550949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Both hemoglobin and hemin cause damage to retinal pigment epithelium through the iron ion accumulation 血红蛋白和血红素都会通过铁离子积累对视网膜色素上皮造成损伤
IF 3.5 3区 医学
Journal of pharmacological sciences Pub Date : 2024-04-02 DOI: 10.1016/j.jphs.2024.04.001
Aomi Muramatsu , Shinsuke Nakamura , Tasuku Hirayama , Hideko Nagasawa , Akihiro Ohira , Takashi Kitaoka , Hideaki Hara , Masamitsu Shimazawa
{"title":"Both hemoglobin and hemin cause damage to retinal pigment epithelium through the iron ion accumulation","authors":"Aomi Muramatsu ,&nbsp;Shinsuke Nakamura ,&nbsp;Tasuku Hirayama ,&nbsp;Hideko Nagasawa ,&nbsp;Akihiro Ohira ,&nbsp;Takashi Kitaoka ,&nbsp;Hideaki Hara ,&nbsp;Masamitsu Shimazawa","doi":"10.1016/j.jphs.2024.04.001","DOIUrl":"https://doi.org/10.1016/j.jphs.2024.04.001","url":null,"abstract":"<div><p>Subretinal hemorrhages result in poor vision and visual field defects. During hemorrhage, several potentially toxic substances are released from iron-based hemoglobin and hemin, inducing cellular damage, the detailed mechanisms of which remain unknown. We examined the effects of excess intracellular iron on retinal pigment epithelial (RPE) cells. A Fe<sup>2+</sup> probe, SiRhoNox-1 was used to investigate Fe<sup>2+</sup> accumulation after treatment with hemoglobin or hemin in the human RPE cell line ARPE-19. We also evaluated the production of reactive oxygen species (ROS) and lipid peroxidation. Furthermore, the protective effect of-an iron chelator, 2,2′-bipyridyl (BP), and ferrostatin-1 (Fer-1) on the cell damage, was evaluated. Fe<sup>2+</sup> accumulation increased in the hemoglobin- or hemin-treated groups, as well as intracellular ROS production and lipid peroxidation. In contrast, BP treatment suppressed RPE cell death, ROS production, and lipid peroxidation. Pretreatment with Fer-1 ameliorated cell death in a concentration-dependent manner and suppressed ROS production and lipid peroxidation. Taken together, these findings indicate that hemoglobin and hemin, as well as subretinal hemorrhage, may induce RPE cell damage and visual dysfunction via intracellular iron accumulation.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"155 2","pages":"Pages 44-51"},"PeriodicalIF":3.5,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000318/pdfft?md5=92ffa2385d8fb2f4f34d446b4ec314f2&pid=1-s2.0-S1347861324000318-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140351933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Imeglimin attenuates NLRP3 inflammasome activation by restoring mitochondrial functions in macrophages Imeglimin 通过恢复巨噬细胞中线粒体的功能来减轻 NLRP3 炎症小体的激活
IF 3.5 3区 医学
Journal of pharmacological sciences Pub Date : 2024-03-27 DOI: 10.1016/j.jphs.2024.03.004
Ji Yeon Lee , Yup Kang , Ja Young Jeon , Hae Jin Kim , Dae Jung Kim , Kwan Woo Lee , Seung Jin Han
{"title":"Imeglimin attenuates NLRP3 inflammasome activation by restoring mitochondrial functions in macrophages","authors":"Ji Yeon Lee ,&nbsp;Yup Kang ,&nbsp;Ja Young Jeon ,&nbsp;Hae Jin Kim ,&nbsp;Dae Jung Kim ,&nbsp;Kwan Woo Lee ,&nbsp;Seung Jin Han","doi":"10.1016/j.jphs.2024.03.004","DOIUrl":"https://doi.org/10.1016/j.jphs.2024.03.004","url":null,"abstract":"<div><p>Imeglimin is a novel oral antidiabetic drug for treating type 2 diabetes. However, the effect of imeglimin on NLRP3 inflammasome activation has not been investigated yet. Here, we aimed to investigate whether imeglimin reduces LPS-induced NLRP3 inflammasome activation in THP-1 macrophages and examine the associated underlying mechanisms. We analyzed the mRNA and protein expression levels of NLRP3 inflammasome components and IL-1β secretion. Additionally, reactive oxygen species (ROS) generation, mitochondrial membrane potential, and mitochondrial permeability transition pore (mPTP) opening were measured by flow cytometry. Imeglimin inhibited NLRP3 inflammasome-mediated IL-1β production in LPS-stimulated THP-1-derived macrophages. In addition, imeglimin reduced LPS-induced mitochondrial ROS production and mitogen-activated protein kinase phosphorylation. Furthermore, imeglimin restored the mitochondrial function by modulating mitochondrial membrane depolarization and mPTP opening. We demonstrated for the first time that imeglimin reduces LPS-induced NLRP3 inflammasome activation by inhibiting mPTP opening in THP-1 macrophages. These results suggest that imeglimin could be a promising new anti-inflammatory agent for treating diabetic complications.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"155 2","pages":"Pages 35-43"},"PeriodicalIF":3.5,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000306/pdfft?md5=f32655537aa9d4a725c45ca52ad8b69c&pid=1-s2.0-S1347861324000306-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140344223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Proteasome inhibitors induce apoptosis by superoxide anion generation via NADPH oxidase 5 in human neuroblastoma SH-SY5Y cells 蛋白酶体抑制剂通过 NADPH 氧化酶 5 在人神经母细胞瘤 SH-SY5Y 细胞中生成超氧阴离子诱导细胞凋亡
IF 3.5 3区 医学
Journal of pharmacological sciences Pub Date : 2024-03-27 DOI: 10.1016/j.jphs.2024.03.002
Akiko Yamamuro-Tanabe, Yu Oshima, Takumi Iyama, Yuki Ishimaru, Yasuhiro Yoshioka
{"title":"Proteasome inhibitors induce apoptosis by superoxide anion generation via NADPH oxidase 5 in human neuroblastoma SH-SY5Y cells","authors":"Akiko Yamamuro-Tanabe,&nbsp;Yu Oshima,&nbsp;Takumi Iyama,&nbsp;Yuki Ishimaru,&nbsp;Yasuhiro Yoshioka","doi":"10.1016/j.jphs.2024.03.002","DOIUrl":"https://doi.org/10.1016/j.jphs.2024.03.002","url":null,"abstract":"<div><p>The ubiquitin-proteasome system (UPS) is a major proteolytic system that plays an important role in the regulation of various cell processes, such as cell cycle, stress response, and transcriptional regulation, especially in neurons, and dysfunction of UPS is considered to be a cause of neuronal cell death in neurodegenerative diseases. However, the mechanism of neuronal cell death caused by UPS dysfunction has not yet been fully elucidated.</p><p>In this study, we investigated the mechanism of neuronal cell death induced by proteasome inhibitors using human neuroblastoma SH-SY5Y cells. Z-Leu-D-Leu-Leu-al (MG132), a proteasome inhibitor, induced apoptosis in SH-SY5Y cells in a concentration- and time-dependent manner. Antioxidants N-acetylcysteine and EUK-8 attenuated MG132-induced apoptosis. Apocynin and diphenyleneiodonium, inhibitors of NADPH oxidase (NOX), an enzyme that produces superoxide anions, also attenuated MG132-induced apoptosis. It was also found that MG132 treatment increased the expression of NOX5, a NOX family member, and that siRNA-mediated silencing of NOX5 and BAPTA-AM, which inhibits NOX5 by chelating calcium, suppressed MG132-induced apoptosis and production of reactive oxygen species in SH-SY5Y cells.</p><p>These results suggest that MG132 induces apoptosis in SH-SY5Y cells through the production of superoxide anion by NOX5.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"155 2","pages":"Pages 52-62"},"PeriodicalIF":3.5,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000288/pdfft?md5=b628cb33348109571b1bba490c2d7965&pid=1-s2.0-S1347861324000288-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140351934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
CSF1R inhibitor PLX3397 depletes microglia in Mongolian gerbil Meriones unguiculatus, but not in syrian hamster Mesocricetus auratus CSF1R 抑制剂 PLX3397 可消耗蒙古沙鼠的小胶质细胞,但不会消耗叙利亚仓鼠的小胶质细胞
IF 3.5 3区 医学
Journal of pharmacological sciences Pub Date : 2024-03-23 DOI: 10.1016/j.jphs.2024.03.003
Ren Y. Sato, Yumin Zhang , Koki T. Kotake , Hiraku Onishi, Shiho Ito, Hiroaki Norimoto, Zhiwen Zhou
{"title":"CSF1R inhibitor PLX3397 depletes microglia in Mongolian gerbil Meriones unguiculatus, but not in syrian hamster Mesocricetus auratus","authors":"Ren Y. Sato,&nbsp;Yumin Zhang ,&nbsp;Koki T. Kotake ,&nbsp;Hiraku Onishi,&nbsp;Shiho Ito,&nbsp;Hiroaki Norimoto,&nbsp;Zhiwen Zhou","doi":"10.1016/j.jphs.2024.03.003","DOIUrl":"10.1016/j.jphs.2024.03.003","url":null,"abstract":"<div><p>Microglia are the residential immune cells in the central nervous system. Their roles as innate immune cells and regulators of synaptic remodeling are critical to the development and the maintenance of the brain. Numerous studies have depleted microglia to elucidate their involvement in healthy and pathological conditions. PLX3397, a blocker of colony stimulating factor 1 receptor (CSF1R), is widely used to deplete mouse microglia due to its non-invasiveness and convenience. Recently, other small rodents, including Syrian hamsters (<em>Mesocricetus auratus</em>) and Mongolian gerbils (<em>Meriones unguiculatus</em>), have been recognized as valuable animal models for studying brain functions and diseases. However, whether microglia depletion via PLX3397 is feasible in these species remains unclear. Here, we administered PLX3397 orally via food pellets to hamsters and gerbils. PLX3397 successfully depleted gerbil microglia but had no effect on microglial density in hamsters. Comparative analysis of the CSF1R amino acid sequence in different species hints that amino acid substitutions in the juxtamembrane domain may potentially contribute to the inefficacy of PLX3397 in hamsters.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"155 2","pages":"Pages 29-34"},"PeriodicalIF":3.5,"publicationDate":"2024-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S134786132400029X/pdfft?md5=adbf8b5c2390572036d58aeb3338ba59&pid=1-s2.0-S134786132400029X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140273890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Upregulation of ATF4 mediates the cellular adaptation to pharmacologic inhibition of amino acid transporter LAT1 in pancreatic ductal adenocarcinoma cells ATF4 的上调介导了胰腺导管腺癌细胞对氨基酸转运体 LAT1 药物抑制的适应性变化
IF 3.5 3区 医学
Journal of pharmacological sciences Pub Date : 2024-03-13 DOI: 10.1016/j.jphs.2024.03.001
Yu Ma , Suguru Okuda , Hiroki Okanishi , Minhui Xu , Chunhuan Jin , Hitoshi Endou , Ryuichi Ohgaki , Yoshikatsu Kanai
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