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In Vitro Anti-inflammatory Activity of Tyrosol and Tryptophol: Metabolites of Yeast via the Ehrlich Pathway.
IF 1.7 4区 医学
Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00625
Toshio Niwa, Yoji Kato, Toshihiko Osawa
{"title":"In Vitro Anti-inflammatory Activity of Tyrosol and Tryptophol: Metabolites of Yeast via the Ehrlich Pathway.","authors":"Toshio Niwa, Yoji Kato, Toshihiko Osawa","doi":"10.1248/bpb.b24-00625","DOIUrl":"https://doi.org/10.1248/bpb.b24-00625","url":null,"abstract":"<p><p>Soy isoflavonoids were applied to commercially available baker's yeast in vitro to find metabolites. Tyrosol, an ingredient in olive oil and wine, and tryptophol were found in the culture media. To test whether tyrosol is a metabolite of soy isoflavonoids, we prepared 2,4-dideuterated equol and applied it to yeast. According to LC-MS analysis of the culture media, deuterated tyrosol was not produced. Therefore, tyrosol is assumed to be a tyrosine metabolite of yeast known as the Ehrlich pathway. We then evaluated the in vitro activities of the 2 amino acid-derived alcohols. Both tyrosol and tryptophol similarly showed anti-inflammatory activity, as evaluated by monocyte chemoattractant protein-1 in 3T3-L1 murine adipocytes in vitro. Our results suggested that the amino acid-derived alcohols may contribute to the anti-inflammatory activity of fermented foods.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 2","pages":"115-118"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405549","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
Stress Response Kinase MK2 Induces Non-canonical Activation of EphA2 in EML4-ALK Lung Cancer Cells.
IF 1.7 4区 医学
Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00747
Fang Zhang, Yue Zhou, Naru Hamada, Akihiro Tanaka, Satoru Yokoyama, Seiji Yano, Kunio Matsumoto, Hiroyuki Mano, Hiroaki Sakurai
{"title":"Stress Response Kinase MK2 Induces Non-canonical Activation of EphA2 in EML4-ALK Lung Cancer Cells.","authors":"Fang Zhang, Yue Zhou, Naru Hamada, Akihiro Tanaka, Satoru Yokoyama, Seiji Yano, Kunio Matsumoto, Hiroyuki Mano, Hiroaki Sakurai","doi":"10.1248/bpb.b24-00747","DOIUrl":"https://doi.org/10.1248/bpb.b24-00747","url":null,"abstract":"<p><p>The non-canonical phosphorylation of the receptor tyrosine kinase ephrin type-A receptor 2 (EphA2) at Ser-897 plays crucial roles in tumor progression in a tyrosine kinase-independent manner. This phosphorylation is catalyzed by p90 ribosomal S6 kinase (RSK), a kinase downstream of extracellular signal-regulated kinase (ERK). We recently reported that stress-responsive kinase mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MK2), instead of ERK, regulates RSK under cellular stress conditions; however, the function of MK2 in ERK-activated cells is still unknown. We herein clarified that MK2 regulates the RSK-EphA2 axis in ERK-activated echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) lung cancer cells. In addition, an MK2 inhibitor blocked enhancements in cell motility induced by the constitutively activated RSK-EphA2 axis. The present results reveal the importance of MK2 in the ERK-activated non-canonical activation of EphA2.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 2","pages":"172-176"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536427","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
Preventive and Therapeutic Effects of Intracerebroventricular Administration of Maresin-1 on Lipopolysaccharide-Induced Depression-Like Behaviors in Mice. 脑室注射maarein -1对小鼠脂多糖诱导的抑郁样行为的防治作用。
IF 1.7 4区 医学
Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00743
Satoshi Deyama, Katsuyuki Kaneda, Masabumi Minami
{"title":"Preventive and Therapeutic Effects of Intracerebroventricular Administration of Maresin-1 on Lipopolysaccharide-Induced Depression-Like Behaviors in Mice.","authors":"Satoshi Deyama, Katsuyuki Kaneda, Masabumi Minami","doi":"10.1248/bpb.b24-00743","DOIUrl":"https://doi.org/10.1248/bpb.b24-00743","url":null,"abstract":"<p><p>Enhanced inflammatory and immune responses have been observed in patients with major depressive disorder, pointing to anti-inflammatory substances as potential seeds for developing novel antidepressants. Omega-3 polyunsaturated fatty acid metabolites, such as resolvin D and E series, maresins, and protectins (collectively known as specialized pro-resolving mediators) demonstrate anti-inflammatory effects. This study examined the antidepressant-like effects of maresin-1 (MaR1) on lipopolysaccharide (LPS)-induced depression-like behaviors in mice. Using the tail suspension test (TST) and the forced swim test (FST), we assessed depression-like behaviors 26 and 28 h after intraperitoneal injection of LPS (0.8 mg/kg), respectively. An open field test (OFT) was also conducted to evaluate locomotor activity 24 h after LPS injection. Intracerebroventricular (i.c.v.) injection of MaR1 (10 ng/mouse) immediately after the LPS challenge mitigated the increased immobility time in the TST and FST, without affecting locomotor activity in the OFT, indicating the preventive effects of MaR1 on LPS-induced depression-like behaviors. Furthermore, i.c.v. injection of MaR1 23 h after the LPS challenge reduced the immobility time in both tests, underscoring its therapeutic potential. These findings suggest that MaR1 could be a promising seed for developing novel antidepressants.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 1","pages":"6-10"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977401","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
Inhibition of LGR5/β-Catenin Axis and Activation of miR134 Are Critically Involved in Apoptotic Effect of Sanggenol L in Hepatocellular Carcinoma.
IF 1.7 4区 医学
Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00213
Jisung Hwang, Deok Yong Sim, Chi-Hoon Ahn, Su-Yeon Park, Jin-Suk Koo, Bum-Sang Shim, Bonglee Kim, Sung-Hoon Kim
{"title":"Inhibition of LGR5/β-Catenin Axis and Activation of miR134 Are Critically Involved in Apoptotic Effect of Sanggenol L in Hepatocellular Carcinoma.","authors":"Jisung Hwang, Deok Yong Sim, Chi-Hoon Ahn, Su-Yeon Park, Jin-Suk Koo, Bum-Sang Shim, Bonglee Kim, Sung-Hoon Kim","doi":"10.1248/bpb.b24-00213","DOIUrl":"https://doi.org/10.1248/bpb.b24-00213","url":null,"abstract":"<p><p>Although Sanggenol L (SL), derived from the root bark of Morus alba, has hepatoprotective, neuroprotective, and antitumor effects, the antitumor mechanism of SL remains unclear to date. Thus, in the current work, the apoptotic mechanisms of SL were investigated in HepG2 and Huh hepatocellular carcinoma (HCC) cells in relation to leucine-rich repeat containing G protein-coupled receptor 5 (LGR5)/β-catenin and miR134 signaling axis. Herein, SL significantly incremented cytotoxicity, sub-G1 population, and the number of terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) positive apoptotic bodies and also inhibited proliferation in HCCs. Consistently, SL activated pro-Caspase7 and pro-Caspase3 and induced the cleavage of Poly ADP-ribose polymerase (PARP) in HCCs. Of note, the pivotal role of LGR5/β-catenin signaling was verified in SL-induced apoptosis in LGR5 overexpressed AML-12 cells and LGR5 depleted HepG2 cells. Furthermore, SL upregulated miR134 expression levels in HepG2 cells, while miR134 inhibitors disturbed the capacity of SL to cleave PARP and pro-Caspase3 in HepG2 cells. Taken together, our findings highlight evidence that inhibition of the LGR5/β-catenin axis and upregulation of miR134 play critical roles in SL-induced apoptosis in HCCs.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 2","pages":"126-131"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432318","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
Recent Antimicrobial Resistance Situation and Mechanisms of Resistance to Key Antimicrobials in Enterotoxigenic Escherichia coli.
IF 1.7 4区 医学
Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00649
Daichi Morita, Teruo Kuroda
{"title":"Recent Antimicrobial Resistance Situation and Mechanisms of Resistance to Key Antimicrobials in Enterotoxigenic Escherichia coli.","authors":"Daichi Morita, Teruo Kuroda","doi":"10.1248/bpb.b24-00649","DOIUrl":"https://doi.org/10.1248/bpb.b24-00649","url":null,"abstract":"<p><p>Enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrhea in developing countries and is regularly imported into developed countries as a major cause of traveler's diarrhea. ETEC is usually self-limiting and not necessarily treated with antimicrobials, although antimicrobial treatment is recommended in malnourished children, severe cases, and traveler's diarrhea. However, resistant strains to representative therapeutic agents such as ciprofloxacin and azithromycin have been reported in recent years, and multidrug-resistant ETEC has also emerged. This review discusses the recent antimicrobial resistance surveillance in ETEC and the mechanisms of resistance to major antimicrobials.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 3","pages":"222-229"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536441","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
Antipruritic Effects of Single Administration of Paroxetine on Acute and Chronic Itch.
IF 1.7 4区 医学
Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00657
Kosuke Matsuda, Hikaru Ishisaka, Masahito Sawahata, Toshiaki Kume, Daisuke Uta
{"title":"Antipruritic Effects of Single Administration of Paroxetine on Acute and Chronic Itch.","authors":"Kosuke Matsuda, Hikaru Ishisaka, Masahito Sawahata, Toshiaki Kume, Daisuke Uta","doi":"10.1248/bpb.b24-00657","DOIUrl":"https://doi.org/10.1248/bpb.b24-00657","url":null,"abstract":"<p><p>Itch is described as an unpleasant sensation, and chronic itch, such as that in atopic dermatitis (AD), often decreases a patient's QOL. There are few effective treatments for various chronic pruritic disorders that are not limited to inflammation. Selective serotonin reuptake inhibitors (SSRIs) are antidepressants used to treat some chronic pruritus disorders. However, there is little evidence from clinical and basic studies using animal models. In this study, we found that paroxetine suppressed acute and chronic itch in mouse models. Single administration of paroxetine (10 mg/kg) inhibited scratching behavior caused by histamine-dependent or histamine-independent itch. Moreover, paroxetine (10 mg/kg) inhibited spontaneous scratching behavior in AD model using NC/Nga mice without affecting locomotor function. These results suggest that paroxetine suppresses chronic itch caused by AD via histamine-dependent and -independent pathways. This study provides one of the few pieces of evidence that SSRIs suppress itch.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 2","pages":"184-187"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536410","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
Change in Vancomycin Absorption after Intraperitoneal Injection and Correlation between Intraperitoneal Vancomycin Absorption and Peritoneal Equilibration Test Score in Mice with Peritoneal Injuries.
IF 1.7 4区 医学
Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00687
Akihiro Moritsuka, Hirotaka Miyamoto, Yukina Takahashi, Haruna Hirata, Yuki Kawauchi, Shintaro Fumoto, Koyo Nishida
{"title":"Change in Vancomycin Absorption after Intraperitoneal Injection and Correlation between Intraperitoneal Vancomycin Absorption and Peritoneal Equilibration Test Score in Mice with Peritoneal Injuries.","authors":"Akihiro Moritsuka, Hirotaka Miyamoto, Yukina Takahashi, Haruna Hirata, Yuki Kawauchi, Shintaro Fumoto, Koyo Nishida","doi":"10.1248/bpb.b24-00687","DOIUrl":"https://doi.org/10.1248/bpb.b24-00687","url":null,"abstract":"<p><p>Peritonitis is a serious complication in peritoneal dialysis patients and requires antibiotic administration. Intraperitoneal vancomycin is an empiric therapy for peritonitis caused by Gram-positive cocci; however, there is no way to predict vancomycin absorption after intraperitoneal administration. Therefore, we aimed to evaluate the changes in vancomycin absorption after intraperitoneal injection into mice with chlorhexidine gluconate (CG) induced peritoneal injuries. Additionally, we examined the correlation between intraperitoneal vancomycin absorption and peritoneal equilibration test (PET) score. PET score was determined using glucose concentration in the peritoneal dialysis fluid at each dwell time (D<sub>t</sub>) and D<sub>2</sub> (2 h of dwell time)/D<sub>0</sub> (0 h of dwell time) glucose ratio. Vancomycin was injected into the peritoneal cavity of mice, blood was collected after 1-8 h, and peritoneal fluid was recovered. The residual ratio of intraperitoneal vancomycin was significantly decreased in the CG group at all time points compared to that in the vehicle group. CG group significantly exhibited higher serum vancomycin concentrations than the vehicle group, and the maximum serum concentration increased depending on CG concentration, with 0.05 and 0.1% CG groups showing 3.9- and 6.1-times higher vancomycin concentrations, respectively, than the vehicle group. A significant correlation was observed between the D<sub>t</sub>/D<sub>0</sub> glucose ratios and residual vancomycin ratios in the peritoneal fluid 2 or 6 h after intraperitoneal injection. A good correlation was observed between the D<sub>2</sub>/D<sub>0</sub> glucose and residual vancomycin ratios 6 h after intraperitoneal vancomycin injection. Thus, PET score can predict residual intraperitoneal vancomycin, aiding in dosing decisions.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 1","pages":"80-85"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078561","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
Longitudinal Trend in Antimicrobial Susceptibility among Haemophilus influenzae: A Single-Centre Study in Japan.
IF 1.7 4区 医学
Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00715
Takeaki Wajima, Naoki Hara, Emi Tanaka, Atsuko Shirai, Kei-Ichi Uchiya
{"title":"Longitudinal Trend in Antimicrobial Susceptibility among Haemophilus influenzae: A Single-Centre Study in Japan.","authors":"Takeaki Wajima, Naoki Hara, Emi Tanaka, Atsuko Shirai, Kei-Ichi Uchiya","doi":"10.1248/bpb.b24-00715","DOIUrl":"https://doi.org/10.1248/bpb.b24-00715","url":null,"abstract":"<p><p>Haemophilus influenzae presents significant concerns regarding antimicrobial resistance. The circumstances surrounding H. influenzae have been changing owing to changes in antimicrobial usage. In the present study, to determine the current situation of H. influenzae, the antimicrobial susceptibility trends were investigated. In total, 21 clinical isolates were analyzed. Antimicrobial susceptibility measured using the broth dilution method was compared with that reported in previous studies at the same hospital. Quinolone low-susceptible isolates were further characterized by multi-locus sequence typing. Upon comparing the susceptibility data in 2022 with those in the past 15 years, the number of β-lactamase nonproducing ampicillin-resistant isolates was decreased. Regarding recent changes, β-lactam-susceptible isolates were found to have gradually increased every year. However, β-lactamase-producing isolates did not decrease. In particular, the ratio of β-lactamase-producing amoxicillin and clavulanic acid-resistant isolates in 2022 was the highest among all the years studied. Moreover, quinolone low-susceptible isolates were still present, suggesting that these isolates could have been indigenized in the community. Furthermore, a β-lactamase-producing amoxicillin and clavulanic acid-resistant isolate was found to have emerged among the quinolone low-susceptibility isolates. At first glance, these findings indicate that antimicrobial resistance has decreased among H. influenzae in clinical settings. However, β-lactamase-producing isolates and quinolone low-susceptible isolates have remained at a constant rate in the community.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 1","pages":"60-64"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078576","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
Pharmacological Profile of NCP-322, a Novel G Protein-Coupled Receptor 119 Agonist, as an Orally Active Therapeutic Agent for Type 2 Diabetes Mellitus.
IF 1.7 4区 医学
Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00737
Hideki Nakamura, Tsuyoshi Endo, Makoto Tsuda
{"title":"Pharmacological Profile of NCP-322, a Novel G Protein-Coupled Receptor 119 Agonist, as an Orally Active Therapeutic Agent for Type 2 Diabetes Mellitus.","authors":"Hideki Nakamura, Tsuyoshi Endo, Makoto Tsuda","doi":"10.1248/bpb.b24-00737","DOIUrl":"https://doi.org/10.1248/bpb.b24-00737","url":null,"abstract":"<p><p>Pharmacological activation of G protein-coupled receptor 119 (GPR119) produces pleiotropic beneficial effects, including the promotion of insulin secretion from pancreatic β-cells, enhancement of glucagon-like peptide (GLP)-1 secretion from intestinal L cells, glucose-dependent insulin secretion, and food intake and body weight gain suppression. Thus, GPR119 has attracted attention as a promising new target for type 2 diabetes mellitus (T2DM) treatment. Here, we identified a new small GPR119 agonist, NCP-322. This compound showed potent enhancing effects on insulin and GLP-1 secretion, which played a role in pancreatic β-cells and intestinal L cells. In the oral glucose tolerance test, NCP-322 administration reduced glycemic excursions that were only exhibited during hyperglycemia. Furthermore, NCP-322 administration did not induce hypoglycemia, the main side effect of antidiabetic drugs. These results suggest the promising therapeutic potential of NCP-322 for T2DM treatment.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 1","pages":"65-74"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078578","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
Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor, FG4592, Induces Endogenous Metallothionein3 Expression in Human Neuronal Cell Line, ReNcell CX Cells.
IF 1.7 4区 医学
Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00792
Mizuki Tsuru, Taisei Ito, Kazuki Komai, Fukuto Kunitomo, Yukie Nakayama, Takanori Murakami, Kazuki Ohuchi, Yasuhiro Shinkai, Tomoki Kimura, Nobuhiko Miura, Yoshito Kumagai, Isao Hozumi, Masatoshi Inden, Hisaka Kurita
{"title":"Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor, FG4592, Induces Endogenous Metallothionein3 Expression in Human Neuronal Cell Line, ReNcell CX Cells.","authors":"Mizuki Tsuru, Taisei Ito, Kazuki Komai, Fukuto Kunitomo, Yukie Nakayama, Takanori Murakami, Kazuki Ohuchi, Yasuhiro Shinkai, Tomoki Kimura, Nobuhiko Miura, Yoshito Kumagai, Isao Hozumi, Masatoshi Inden, Hisaka Kurita","doi":"10.1248/bpb.b24-00792","DOIUrl":"https://doi.org/10.1248/bpb.b24-00792","url":null,"abstract":"<p><p>Metallothionein (MT) is a small-molecule protein that functions in essential trace element homeostasis. Among MT isoforms, MT3 is involved in neuronal activity, and its expression is reported to be decreased in patients with neurodegenerative conditions such as Alzheimer's disease; however, only a few effective drugs have been reported to induce MT3 expression. In this study, we evaluated existing drugs for the induction of MT3 expression in the neuronal cell line of ReNcell CX cells. Using recombinant proteins of MT isoforms with the 3× Flag tag, we performed Western blotting (WB) with the primary antibodies against MT3 or Flag tag, and this method of WB for MT3 was confirmed specifically to detect the MT3 protein. We treated ReNcell CX cells with several HIF-PH inhibitors and evaluated MT3 expression via real-time RT-PCR. We found that FG4592 significantly enhanced MT3 expression at both RNA and protein levels. FG4592 treatment increased the amount of hypoxia-inducible factor 1 alpha (HIF1α) binding to the MT3 promoter. These findings indicate that FG4592 induces MT3 expression via increased HIF1α. In conclusion, we found FG4592 to be an endogenous MT3 inducer in the cells of the nervous system in this study. The findings of this study are expected to lead to the development of new MT3-inducing drugs for neurodegenerative diseases based on FG4592.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 2","pages":"137-143"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490668","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
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