Biological & pharmaceutical bulletin最新文献_第9页

Antiarrhythmic Potential of the β-Adrenoceptor Blocker Metoprolol against Dofetilide-Induced Torsades de Pointes in Anesthetized Bradycardic Rabbits. β-肾上腺素受体阻滞剂美托洛尔对麻醉心动过缓兔多非利特诱发的点扭转的抗心律失常电位。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b25-00450

Satoshi Kawakami, Yuki Ishimaru, Megumi Aimoto, Yoshinobu Nagasawa, Akira Takahara

{"title":"Antiarrhythmic Potential of the β-Adrenoceptor Blocker Metoprolol against Dofetilide-Induced Torsades de Pointes in Anesthetized Bradycardic Rabbits.","authors":"Satoshi Kawakami, Yuki Ishimaru, Megumi Aimoto, Yoshinobu Nagasawa, Akira Takahara","doi":"10.1248/bpb.b25-00450","DOIUrl":"https://doi.org/10.1248/bpb.b25-00450","url":null,"abstract":"We have established a proarrhythmic rabbit model of acute atrioventricular block (AVB) with severe bradycardia to detect delayed rectifier K+ channel current (IKr) blocker-induced torsade de pointes (TdP). To better understand the role of β-adrenoceptors in this model, we investigated the effect of the β-adrenoceptor blocker metoprolol against an IKr blocker dofetilide-induced TdP. AVB was induced by catheter ablation under isoflurane anesthesia, and the ventricles were electrically paced at a constant rate of 60 beats/min throughout the experiments. Monophasic action potentials (MAPs) were recorded from the right ventricle. In the non-treated control rabbits (n = 5), intravenous administration of an IKr blocker dofetilide (25 µg/kg) prolonged the MAP duration (MAP90) by 90 ± 38 ms, which led to the induction of TdP in four of the five animals. In rabbits receiving the β-adrenoceptor blocker metoprolol (10 µg/kg/min, n = 5), the same dose of dofetilide prolonged MAP90 by 205 ± 31 ms, whereas TdP did not occur in this group. Meanwhile, the incidence of dofetilide-induced R-on-T-type premature ventricular contractions, representing an arrhythmogenic trigger, was lower in metoprolol-treated rabbits than in non-treated control rabbits. These results indicate that metoprolol exerted an overall antiarrhythmic effect by strongly suppressing TdP generation induced by dofetilide, despite its proarrhythmic action of enhancing repolarization prolongation. This highlights the critical role of β-adrenoceptors in facilitating arrhythmogenic triggers under conditions of excessive repolarization delay.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 1","pages":"34-39"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145899184","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

Real-World Medication Regimen Change in Adults with ADHD: A Large Claims Database Study. 现实世界中ADHD成人药物治疗方案的改变：一项大型索赔数据库研究。

IF 1.8 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b26-00127

Natsuri Yonezawa, Kenji Momo

{"title":"Real-World Medication Regimen Change in Adults with ADHD: A Large Claims Database Study.","authors":"Natsuri Yonezawa, Kenji Momo","doi":"10.1248/bpb.b26-00127","DOIUrl":"https://doi.org/10.1248/bpb.b26-00127","url":null,"abstract":"Pharmacotherapy persistence in adults with attention-deficit/hyperactivity disorder (ADHD) remains concerning; however, evidence describing early treatment changes and discontinuation is limited. This study aimed to describe initial ADHD pharmacotherapy patterns and quantify claims-based initial regimen instability in Japanese adults. Using a Japanese claims database, we assembled a cohort of adults who initiated ADHD medication with methylphenidate, atomoxetine, guanfacine, or polytherapy (combination therapy) at initiation. Initial regimen instability was defined as the first observed regimen modification, including switching, add-on/polytherapy, de-escalation or combination-pattern change among initial polytherapy users, or a temporary drug-free interruption followed by restart after 31-179 d. A sustained medication-free period of ≥180 d without restart was treated as a competing event. We estimated cumulative incidence functions for initial regimen instability, treating the sustained medication-free period as a competing event. Fine-Gray models adjusted for age, sex, and major psychiatric comorbidities were used to compare initial regimens with methylphenidate as a reference. Landmark analysis was used to assess robustness. Among 14814 initiators, 3085, 8517, 3076, and 136 started methylphenidate, atomoxetine, guanfacine, and initial polytherapy, respectively. In the adjusted Fine-Gray model, the subdistribution hazard ratio for initial regimen instability was 0.74 for atomoxetine and 0.72 for guanfacine, whereas it was higher (2.65) for initial polytherapy in the main analysis. However, this estimate was sensitive to the operational definition of regimen instability. Landmark analysis yielded consistent differences between regimens. Initial ADHD pharmacotherapy showed heterogeneity in Japanese adults and included initial polytherapy, with initial regimen instability differing substantially depending on the starting regimen.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 8","pages":"1263-1270"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148787920","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

Critical Medicines Lists in Japan and the European Union: Insights into Supply Resilience and Policy Priorities. 日本和欧盟的关键药物清单：对供应弹性和政策优先事项的见解。

IF 1.8 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b26-00220

Ken-Ichi Izutsu, Shoto Sasaki, Rin Kondo, Karen Namiki, Hideaki Uzawa, Hiroaki Mamiya

{"title":"Critical Medicines Lists in Japan and the European Union: Insights into Supply Resilience and Policy Priorities.","authors":"Ken-Ichi Izutsu, Shoto Sasaki, Rin Kondo, Karen Namiki, Hideaki Uzawa, Hiroaki Mamiya","doi":"10.1248/bpb.b26-00220","DOIUrl":"10.1248/bpb.b26-00220","url":null,"abstract":"Regulatory authorities are increasingly developing lists of medicines that are at high risk of shortage to strengthen supply chain resilience. This study compares Japan's Ministry of Health, Labour and Welfare (MHLW) List of Medicines for Stable Supply with the European Medicines Agency (EMA) Union List of Critical Medicines, examining their regulatory roles, selection criteria, and composition using the WHO Anatomical Therapeutic Chemical classification. For antibacterial and antineoplastic agents, we also analyzed mechanisms of action, approval years, and inclusion on the WHO Essential Medicines List. The EMA list primarily includes medicines whose supply interruption would pose an immediate and serious threat to life or essential medical care over a limited period. This narrower scope, with fewer chronic disease medicines, such as antihypertensives and therapies for bone-related diseases and endocrine disorders, reflects strict criteria focused on life-sustaining importance amid economic security risks, including import disruptions. Conversely, the MHLW list is substantially broader. It encompasses not only life-saving medicines but also many chronic disease treatments, whose interruption would have less immediate clinical impact, as well as vitamins, minerals, and diagnostic agents. For antibacterial and antineoplastic agents, both lists include older, well-established medicines, whereas the MHLW-only group contains newer agents reflecting Japanese clinical practice. Although the broad scope of the MHLW list supports routine supply management, it is less suited to rapid prioritization during large-scale shortages driven by external factors. Clarifying risk scenarios and identifying priority medicines may enhance emergency response capacities.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 9","pages":"1482-1490"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148918438","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

Sequestration of CAPNS1 into Polyglycine Aggregates in a Cellular Model of NOTCH2NLC Repeat Expansion. NOTCH2NLC重复扩增细胞模型中CAPNS1在聚甘氨酸聚集体中的固存

IF 1.8 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b26-00313

Arisa Kubokawa, Ai Ohki, Risa Ono, Makoto Araki, Motoaki Yanaizu, Yoshihiro Kino

{"title":"Sequestration of CAPNS1 into Polyglycine Aggregates in a Cellular Model of NOTCH2NLC Repeat Expansion.","authors":"Arisa Kubokawa, Ai Ohki, Risa Ono, Makoto Araki, Motoaki Yanaizu, Yoshihiro Kino","doi":"10.1248/bpb.b26-00313","DOIUrl":"https://doi.org/10.1248/bpb.b26-00313","url":null,"abstract":"Neuronal Intranuclear Inclusion Disease (NIID) is caused by GGC repeat expansions in the 5' untranslated region of the notch 2 N-terminal like C (NOTCH2NLC) gene. An upstream open reading frame within the mutant transcript produces the NOTCH2NLC upstream open reading frame-derived polyglycine protein (uN2CpolyG) containing expanded polyglycine (polyG), which forms intranuclear inclusions. Although uN2CpolyG is thought to play a critical role in disease pathogenesis, the mechanisms underlying its toxicity and inclusion formation remain incompletely understood. In this study, we first expressed a pure GGC repeat encoding polyG in Neuro2a cells and identified aggregate-associated proteins by mass spectrometry. We then confirmed the formation of intracellular aggregates using both transient expression and drug-inducible expression systems for uN2CpolyG. Among the proteins identified by mass spectrometry, Calpain small subunit 1 (Capns1), the regulatory subunit of calpain, was found to be sequestered into uN2CpolyG aggregates. Notably, the N-terminus of Capns1 contains a glycine-rich sequence, which mediated its co-aggregation with uN2CpolyG. Furthermore, knockdown of Capns1 appeared to reduce the accumulation of uN2CpolyG aggregates. Collectively, these findings identify Capns1 as a potential modifier of NIID pathology.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 9","pages":"1404-1408"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148879029","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 ONO-6950, a Novel Dual Cysteinyl Leukotriene 1 and 2 Receptor Antagonist, in a Rat Model of Pulmonary Arterial Hypertension. 新型双半胱氨酸-白三烯1和2受体拮抗剂ONO-6950在肺动脉高压大鼠模型中的作用

IF 1.8 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b26-00345

Akihiro Kamiya, Masabumi Minami

{"title":"Effects of ONO-6950, a Novel Dual Cysteinyl Leukotriene 1 and 2 Receptor Antagonist, in a Rat Model of Pulmonary Arterial Hypertension.","authors":"Akihiro Kamiya, Masabumi Minami","doi":"10.1248/bpb.b26-00345","DOIUrl":"https://doi.org/10.1248/bpb.b26-00345","url":null,"abstract":"The effects of ONO-6950, a novel dual antagonist of cysteinyl leukotriene 1 (CysLT1) and 2 (CysLT2) receptors, were examined in a monocrotaline-induced rat model of pulmonary arterial hypertension (PAH). The effects were compared with those of montelukast (selective CysLT1 receptor antagonist), bosentan (endothelin receptor antagonist), and imatinib (tyrosine kinase inhibitor). In the rat PAH model, ONO-6950 (10, 30, or 100 mg/kg, p.o.) and bosentan (50 mg/kg, p.o.) significantly ameliorated right ventricular hypertrophy and elevation of right ventricular pressure, both indices of PAH, whereas montelukast showed only limited efficacy. Histopathological evaluation revealed that ONO-6950 showed a weak trend toward improvement in pulmonary vascular remodeling and inflammatory cell infiltration in lung tissue. Furthermore, ONO-6950 and imatinib similarly prolonged survival in the rat PAH model. These results demonstrate that ONO-6950 is an orally active dual CysLT1/CysLT2 receptor antagonist that may provide a novel therapeutic option for PAH.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 10","pages":"1659-1666"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164797","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

Enhancing Skin Penetration of a Hydrophilic, Large Molecular Weight Compound Using a Nanoparticle-in-Oil Dispersion. 利用纳米颗粒油内分散体增强亲水性大分子量化合物的皮肤渗透。

IF 1.8 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b26-00242

Hikaru Machida, Hiroaki Sato, Tomohiro Hikima

{"title":"Enhancing Skin Penetration of a Hydrophilic, Large Molecular Weight Compound Using a Nanoparticle-in-Oil Dispersion.","authors":"Hikaru Machida, Hiroaki Sato, Tomohiro Hikima","doi":"10.1248/bpb.b26-00242","DOIUrl":"https://doi.org/10.1248/bpb.b26-00242","url":null,"abstract":"The hyaluronic acid levels in the body decline over time due to various factors, such as aging and UV irradiation. Therefore, technologies that can directly deliver hyaluronic acid across the skin are clinically relevant. In this study, we fabricated a nanoparticle-in-oil dispersion (NOD) by dehydrating a water-in-oil emulsion containing rhodamine B isothiocyanate-labeled sodium hyaluronate (RHA; average molecular weight, 1200000-1600000). To clarify the effect of NOD on the transdermal absorption of RHA, in vitro experiments were performed using three formulations: RHA-loaded NOD (RHA-NOD), an olive oil dispersion of RHA (RHA-O) containing a surfactant (polyglyceryl-6 polyricinoleate), and an olive oil dispersion of RHA (oil dispersion). The RHA concentrations in the RHA-NOD, RHA-O, and oil dispersion, each prepared at 0.03% (w/v), were 144.5 ± 9.1, 2.5 ± 0.3, and 4.0 × 10-2 ± 0.3 × 10-2 µg/mL, respectively. Dynamic light-scattering and field emission scanning electron microscopy revealed a uniform size of 150 nm for the NOD. The skin penetration flux of the RHA-NOD was 3.4 times that of RHA-O. Analysis of cryosections indicated that NOD significantly increased the RHA concentration from the skin surface to a depth of 140 µm. These findings position NODs as platforms with the potential to maintain a high concentration of RHA on the skin surface.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 9","pages":"1570-1577"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149069122","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

An in Vivo Factor Connecting Sustained Reactive Oxygen Species Capture with Rapid Disposition: Quercetin Distribution into Hemoglobin. 连接持续活性氧捕获与快速处置的体内因子：槲皮素在血红蛋白中的分布。

IF 1.8 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b26-00207

Tadatoshi Tanino, Yukari Ueda, Noriaki Nagai, Yoshinori Funakami, Kimihisa Itoh

{"title":"An in Vivo Factor Connecting Sustained Reactive Oxygen Species Capture with Rapid Disposition: Quercetin Distribution into Hemoglobin.","authors":"Tadatoshi Tanino, Yukari Ueda, Noriaki Nagai, Yoshinori Funakami, Kimihisa Itoh","doi":"10.1248/bpb.b26-00207","DOIUrl":"https://doi.org/10.1248/bpb.b26-00207","url":null,"abstract":"The in vivo antioxidant effects of freely available quercetin (Qc) on human health are poorly defined by Qc pharmacokinetics, with high binding capacity to plasma albumin, wide distribution, and a short half-life. To pharmacokinetically investigate reactive oxygen species (ROS)-scavenging pathways of Qc, we focused on in vivo upstream factors (splenic macrophage-generated ROS and deformed erythrocytes) of mouse acetaminophen (APAP)-induced liver damage. Qc co-treatment rescued the hepatic accumulation of blood cells and deformed blood cells without affecting APAP metabolite-blood cell adduct levels. It clearly reduced lipid hydroperoxidation of blood cells after APAP overdose, suggesting in vivo protective effects against splenic ROS attack. Our in vitro data with Qc derivatives showed that the 3-, 3'-, and 4'-OH groups in the Qc molecule participated in formation of the Qc-blood cell complex. 5-Hydroxyl-lacking fisetin competitively bound to Qc-binding site(s) in the mouse hemoglobin (Hb) protein molecule. When Qc was injected into mice, crude Hb strongly interacted with Qc even after 3 h, differing from rapid Qc disposition within 30 min from plasma. The Qc-Hb interaction suggested a source of the short half-life and wide distribution of Qc. Therefore, we suggest that rapid formation of the Qc-Hb protein complex is essential in determining an in vivo upstream factor connecting in vivo ROS-scavenging effects with Qc disposition. When Qc is intravenously and orally administered, the Qc-Hb protein complex rather than Qc in plasma is an important factor in analyzing Qc pharmacokinetics, leading to determination of intake safely available for human healthcare and re-evaluation of the poor Qc bioavailability reported.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 9","pages":"1550-1560"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149069184","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

Photoacoustic Imaging for Monitoring Calcium Dynamics in the Heart. 光声成像监测心脏钙动态。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b25-00467

Daiki Kyono, Ryota Matsuzaki, Daichi Kawata, Hiryu Mikami, Yoshiki Murano, Ichiro Shoji, Hiroaki Suzuki, Naoya Nakahara, Shingo Murakami

{"title":"Photoacoustic Imaging for Monitoring Calcium Dynamics in the Heart.","authors":"Daiki Kyono, Ryota Matsuzaki, Daichi Kawata, Hiryu Mikami, Yoshiki Murano, Ichiro Shoji, Hiroaki Suzuki, Naoya Nakahara, Shingo Murakami","doi":"10.1248/bpb.b25-00467","DOIUrl":"10.1248/bpb.b25-00467","url":null,"abstract":"Photoacoustic imaging (PAI) is a hybrid imaging modality that captures ultrasound signals produced by thermoelastic expansion when pulsed laser light is absorbed by optical absorbers, enabling visualization of biological tissues at greater depths than those of conventional fluorescence imaging. While PAI has been conventionally used for biological, structural, and morphological studies, showing promise for imaging calcium dynamics in cardiac tissue, its practical implementation remains undemonstrated. In this study, we implemented a sectional excitation strategy using a thin, sheet-shaped laser beam to confine optical excitation to defined tissue planes. We applied this approach to photoacoustic imaging of a perfused bullfrog heart loaded with liposome-encapsulated calcium-sensitive dye. We successfully achieved real-time visualization of calcium dynamics within the atrial cross-section, while simultaneous electrocardiographic recordings enabled temporal correlation between photoacoustic signal fluctuations and cardiac electrical activity. This method provides a less-invasive approach to assess calcium transients in deep tissue, and broadens the application of PAI from morphology to physiological function. These findings highlight the potential of this optical-acoustic hybrid modality as a powerful tool for calcium imaging in physiological and pharmacological studies involving deep-tissue organs-particularly in applications such as heart imaging, where conventional optical techniques are limited by shallow penetration depth.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 1","pages":"30-33"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145899208","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

Interlaboratory Method Validation for Determination of Polysorbate 80 for Analysis of mAbs. 用于单克隆抗体分析的聚山梨酯80的实验室间方法验证。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b25-00345

Xiaojuan Yu, Feiyu Wang, Chuanfei Yu, Lan Wang

引用次数: 0

Role of Mitochondrial Protein, mitoNEET, in Impaired Intracellular Cholesterol Metabolism-Induced Neuronal Cell Death. 线粒体蛋白mitoNEET在受损细胞内胆固醇代谢诱导的神经元细胞死亡中的作用

IF 1.8 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b25-00334

Ayana Nakata, Tsugumi Takeo, Hideya Mizuno

{"title":"Role of Mitochondrial Protein, mitoNEET, in Impaired Intracellular Cholesterol Metabolism-Induced Neuronal Cell Death.","authors":"Ayana Nakata, Tsugumi Takeo, Hideya Mizuno","doi":"10.1248/bpb.b25-00334","DOIUrl":"10.1248/bpb.b25-00334","url":null,"abstract":"Parkinson's disease (PD) is a progressive neurological disorder with an unclear etiology. Nonetheless, abnormal cholesterol metabolism is considered an environmental risk factor. MitoNEET (mNT) is an iron-sulfur cluster protein located in the outer mitochondrial membrane. mNT dysfunction is involved in the pathology of several diseases, including PD. However, the cause of mNT dysfunction remains unclear. Therefore, we hypothesized that increased intracellular cholesterol levels may reduce mNT function and increase reactive oxygen species (ROS) levels, resulting in neuronal cell death and PD progression. In this study, we investigated the effects of cholesterol on cell viability and mNT levels in human neuroblastoma (SH-SY5Y) cells. Cholesterol reduced cell viability and mNT protein levels and increased ROS generation. Pioglitazone, an mNT activator, decreased cholesterol-induced ROS generation but did not rescue cell viability, suggesting that reduced mNT levels may be involved but are not the sole cause of cholesterol-induced cell death. Additionally, the viability of cells treated with rotenone, 6-hydroxydopamine, and 1-methyl-4-phenylpyridinium in the presence of cholesterol was measured. However, no significant enhancement in cell death was observed. Moreover, the toxic compounds did not reduce mNT levels, indicating that mNT is not involved in toxic compound-induced cell death. In summary, these results indicate that cholesterol induces cell death, reduces mNT protein levels without suppressing transcription, and increases ROS generation, which may affect PD development. Further assessment of the mechanisms associated with abnormal intracellular cholesterol metabolism, reduced mNT levels, and cell death may lead to the discovery of novel treatments for PD.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 1","pages":"154-161"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046051","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