Biological & pharmaceutical bulletin最新文献_第4页

Dictamnine Ameliorates DNFB-Induced Atopic Dermatitis Like Skin Lesions in Mice by Inhibiting M1 Macrophage Polarization and Promoting Autophagy. 地克明通过抑制 M1 巨噬细胞极化和促进自噬，改善 DNFB 诱导的小鼠特应性皮炎样皮损。

IF 2 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-01-13 Epub Date: 2023-12-13 DOI: 10.1248/bpb.b23-00436

Yihan Huang, Chenrui Zhao, Guodong Zheng, Yujuan Yuan, Ling Gong, Rui Liu, Jingang An

{"title":"Dictamnine Ameliorates DNFB-Induced Atopic Dermatitis Like Skin Lesions in Mice by Inhibiting M1 Macrophage Polarization and Promoting Autophagy.","authors":"Yihan Huang, Chenrui Zhao, Guodong Zheng, Yujuan Yuan, Ling Gong, Rui Liu, Jingang An","doi":"10.1248/bpb.b23-00436","DOIUrl":"10.1248/bpb.b23-00436","url":null,"abstract":"Autophagy and M1 macrophage polarization play important roles in the regulation of inflammation in atopic dermatitis (AD). Dictamnine is one of the main ingredients in Cortex Dictamni, a widely used traditional Chinese medicine for the treatment of dermatitis. In the present study, we investigated the anti-inflammatory effects of dictamnine on AD like skin lesions and M1 macrophage polarization. A 2,4-dinitrofluorobenzene (DNFB) triggered AD like skin lesions models in mice was established to identify the ameliorative effects of dictamnine on AD in vivo. In addition, an M1 macrophage polarization model was co-stimulated by lipopolysaccharide (LPS) and interferon-γ (IFN-γ) using phorbol myristate acetate (PMA) differentiated THP-1 cells, to investigate the effect of dictamnine on promoting autophagy and inhibiting inflammatory factor release. Dictamnine suppressed DNFB-induced skin inflammation by inhibiting M1 macrophage polarization, up-regulating the expression of microtubule-associated protein 1A/1B-light chain 3 (LC3) expression, and promoting macrophage autophagy at inflammatory sites. Dictamnine also could reduce the release of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), and interleukin-8 (IL-8), and down-regulate the mRNA expression of these genes in LPS-IFN-γ triggered M1 polarized macrophages. Dictamnine ameliorates AD like skin lesions by inhibiting M1 macrophage polarization and promoting autophagy. Hence, dictamnine is expected to be a potential therapeutic candidate for AD.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138797447","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

Combined Experiments with in Vivo Fiber Photometry and Behavior Tests Can Facilitate the Measurement of Neuronal Activity in the Primary Somatosensory Cortex and Hyperalgesia in an Inflammatory Pain Mice Model. 体内纤维光度测定与行为测试相结合的实验有助于测量炎症性疼痛小鼠模型中初级躯体感觉皮层的神经元活动和痛觉减退。

IF 2 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/bpb.b23-00700

Tatsuya Ishikawa, Daisuke Uta, Hiroaki Okuda, Ilia Potapenko, Kiyomi Hori, Toshiaki Kume, Noriyuki Ozaki

{"title":"Combined Experiments with in Vivo Fiber Photometry and Behavior Tests Can Facilitate the Measurement of Neuronal Activity in the Primary Somatosensory Cortex and Hyperalgesia in an Inflammatory Pain Mice Model.","authors":"Tatsuya Ishikawa, Daisuke Uta, Hiroaki Okuda, Ilia Potapenko, Kiyomi Hori, Toshiaki Kume, Noriyuki Ozaki","doi":"10.1248/bpb.b23-00700","DOIUrl":"10.1248/bpb.b23-00700","url":null,"abstract":"The pain matrix, which includes several brain regions that respond to pain sensation, contribute to the development of chronic pain. Thus, it is essential to understand the mechanism of causing chronic pain in the pain matrix such as anterior cingulate (ACC), or primary somatosensory (S1) cortex. Recently, combined experiment with the behavior tests and in vivo calcium imaging using fiber photometry revealed the interaction between the neuronal function in deep brain regions of the pain matrix including ACC and the phenotype of chronic pain. However, it remains unclear whether this combined experiment can identify the interaction between neuronal activity in S1, which receive pain sensation, and pain behaviors such as hyperalgesia or allodynia. In this study, to examine whether the interaction between change of neuronal activity in S1 and hyperalgesia in hind paw before and after causing inflammatory pain was detected from same animal, the combined experiment of in vivo fiber photometry system and von Frey hairs test was applied. This combined experiment detected that amplitude of calcium responses in S1 neurons increased and the mechanical threshold of hind paw decreased from same animals which have an inflammatory pain. Moreover, we found that the values between amplitude of calcium responses and mechanical thresholds were shifted to negative correlation after causing inflammatory pain. Thus, the combined experiment with fiber photometry and the behavior tests has a possibility that can simultaneously consider the interaction between neuronal activity in pain matrix and pain induced behaviors and the effects of analgesics or pain treatments.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140048678","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

Platelets Affect the Activity of Amino Acid Transporter SNAT4 in HuH-7 Human Hepatoma Cells. 血小板影响 HuH-7 人肝癌细胞中氨基酸转运体 SNAT4 的活性

IF 2 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/bpb.b23-00904

Hitoshi Kashiwagi, Yuki Sato, Shunsuke Nashimoto, Shungo Imai, Yoh Takekuma, Mitsuru Sugawara

{"title":"Platelets Affect the Activity of Amino Acid Transporter SNAT4 in HuH-7 Human Hepatoma Cells.","authors":"Hitoshi Kashiwagi, Yuki Sato, Shunsuke Nashimoto, Shungo Imai, Yoh Takekuma, Mitsuru Sugawara","doi":"10.1248/bpb.b23-00904","DOIUrl":"10.1248/bpb.b23-00904","url":null,"abstract":"Platelets have been reported to exert diverse actions besides hemostasis and thrombus formation in the body. However, whether platelets affect transporter activity remains to be determined. In this study, we examined the effects of platelets on the activity of amino acid transporter system A, which is known to be changed by various factors, and we clarified the mechanism by which platelets affect system A activity. Among system A subtypes, we found that sodium-coupled neutral amino acid transporter (SNAT) 4 played a central role in the transport activity of system A in HuH-7 human hepatoma cells. Interestingly, platelets showed a biphasic effect on system A activity: activated platelet supernatants (APS) including the granule contents released from platelets downregulated system A activity at lower concentrations and the downregulation was suppressed at higher concentrations. The downregulation was due to a decrease in the affinity of SNAT4 for its substrate and not a decrease in the SNAT4 abundance on the plasma membrane. In addition, APS did not decrease the expression level of SNAT4 mRNA. On the other hand, platelets did not affect system A activity when the platelet suspension was added to HuH-7 cells. These results indicate that platelets indirectly affect the transport activity of system A by releasing bioactive substances but do not directly affect it by binding to HuH-7 cells.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140179298","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

Inhibitory Actions of Antidepressants, Hypnotics, and Anxiolytics on Recombinant Human Acetylcholinesterase Activity. 抗抑郁药、催眠药和抗焦虑药对重组人乙酰胆碱酯酶活性的抑制作用

IF 2 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/bpb.b23-00719

Keisuke Obara, Haruka Mori, Suzune Ihara, Kento Yoshioka, Yoshio Tanaka

{"title":"Inhibitory Actions of Antidepressants, Hypnotics, and Anxiolytics on Recombinant Human Acetylcholinesterase Activity.","authors":"Keisuke Obara, Haruka Mori, Suzune Ihara, Kento Yoshioka, Yoshio Tanaka","doi":"10.1248/bpb.b23-00719","DOIUrl":"10.1248/bpb.b23-00719","url":null,"abstract":"Alzheimer's disease (AD) is accompanied by behavioral and psychological symptoms of dementia (BPSD), which is often alleviated by treatment with psychotropic drugs, such as antidepressants, hypnotics, and anxiolytics. If these drugs also inhibit acetylcholinesterase (AChE) activity, they may contribute to the suppression of AD progression by increasing brain acetylcholine concentrations. We tested the potential inhibitory effects of 31 antidepressants, 21 hypnotics, and 12 anxiolytics on recombinant human AChE (rhAChE) activity. At a concentration of 10-4 M, 22 antidepressants, 19 hypnotics, and 11 anxiolytics inhibited rhAChE activity by <20%, whereas nine antidepressants (clomipramine, amoxapine, setiptiline, nefazodone, paroxetine, sertraline, citalopram, escitalopram, and mirtazapine), two hypnotics (triazolam and brotizolam), and one anxiolytic (buspirone) inhibited rhAChE activity by ≥20%. Brotizolam (≥10-6 M) exhibited stronger inhibition of rhAChE activity than the other drugs, with its pIC50 value being 4.57 ± 0.02. The pIC50 values of the other drugs were <4, and they showed inhibitory activities toward rhAChE at the following concentrations: ≥3 × 10-6 M (sertraline and buspirone), ≥10-5 M (amoxapine, nefazodone, paroxetine, citalopram, escitalopram, mirtazapine, and triazolam), and ≥3 × 10-5 M (clomipramine and setiptiline). Among these drugs, only nefazodone inhibited rhAChE activity within the blood concentration range achievable at clinical doses. Therefore, nefazodone may not only improve the depressive symptoms of BPSD through its antidepressant actions but also slow the progression of cognitive symptoms of AD through its AChE inhibitory actions.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139696917","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

Errata for Biological and Pharmaceutical Bulletin. 生物与制药公报》勘误表。

IF 2 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/bpb.b24-e4702

引用次数: 0

Potential Therapeutic Strategies and Drugs That Target Vascular Permeability in Severe Infectious Diseases. 针对严重传染病血管通透性的潜在治疗策略和药物。

IF 2 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/bpb.b24-00028

Yoshiaki Okada

{"title":"Potential Therapeutic Strategies and Drugs That Target Vascular Permeability in Severe Infectious Diseases.","authors":"Yoshiaki Okada","doi":"10.1248/bpb.b24-00028","DOIUrl":"10.1248/bpb.b24-00028","url":null,"abstract":"Severe infection pathogenicity is induced by processes such as pathogen exposure, immune cell activation, inflammatory cytokine production, and vascular hyperpermeability. Highly effective drugs, such as antipathogenic agents, steroids, and antibodies that suppress cytokine function, have been developed to treat the first three processes. However, these drugs cannot completely suppress severe infectious diseases, such as coronavirus disease 2019 (COVID-19). Therefore, developing novel drugs that inhibit vascular hyperpermeability is crucial. This review summarizes the mechanisms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced vascular hyperpermeability and identifies inhibitors that increase endothelial cell (EC) junction-related proteins and determines their efficacy in COVID-19 and endotoxemia models. Analyzing the effects of SARS-CoV-2 on vascular permeability revealed that SARS-CoV-2 suppresses Claudin-5 (CLDN5) expression, which is responsible for adhesion between ECs, thereby increasing vascular permeability. Inhibiting CLDN5 function in mice induced vascular hyperpermeability and pulmonary edema. In contrast, Enhancing CLDN5 expression suppressed SARS-CoV-2-induced endothelial hyperpermeability, suggesting that SARS-CoV-2-induced vascular hyperpermeability contributes to pathological progression, which can be suppressed by upregulating EC junction proteins. Based on these results, we focused on Roundabout4 (Robo4), another EC-specific protein that stabilizes EC junctions. EC-specific Robo4 overexpression suppressed vascular hyperpermeability and mortality in lipopolysaccharide-treated mice. An ALK1 inhibitor (a molecule that increases Robo4 expression), suppressed vascular hyperpermeability and mortality in lipopolysaccharide- and SARS-CoV-2-treated mice. These results indicate that Robo4 expression-increasing drugs suppress vascular permeability and pathological phenotype in COVID-19 and endotoxemia models.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140020888","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

Expression of Epithelial-Mesenchymal Transition Markers in Epidermal Layer of Atopic Dermatitis. 特应性皮炎表皮层上皮-间质转化标志物的表达

IF 2 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/bpb.b23-00291

Kazuyuki Kitazawa, Kazunori Tanaka, Yoshiki Kubota, Mina Musashi, Kiyoshi Higashi, Teruaki Nagasawa, Miyuki Kobayashi, Tatsuro Kamakura, Rie Igarashi, Yoko Yamaguchi

{"title":"Expression of Epithelial-Mesenchymal Transition Markers in Epidermal Layer of Atopic Dermatitis.","authors":"Kazuyuki Kitazawa, Kazunori Tanaka, Yoshiki Kubota, Mina Musashi, Kiyoshi Higashi, Teruaki Nagasawa, Miyuki Kobayashi, Tatsuro Kamakura, Rie Igarashi, Yoko Yamaguchi","doi":"10.1248/bpb.b23-00291","DOIUrl":"10.1248/bpb.b23-00291","url":null,"abstract":"The epithelial-mesenchymal transition (EMT) is a phenomenon, in which epithelial cells acquire a mesenchymal cell phenotype. It is important during wound healing; however, chronic inflammation leads to excessive EMT and causes tissue barrier dysfunction with hyperplasia. EMT is induced by several cytokines, such as interleukin (IL)-4 and IL-13. Additionally, IL-4 and IL-13 are known to increase in atopic dermatitis (AD) characterized by intense itching and eczema. Therefore, we assumed that there was commonality between the respective EMT and AD phenotypes. Herein, we evaluated EMT marker expression in AD skin and demonstrated that EMT-maker Snai1 and Twist expression were increased in AD mice model and patients with AD. Moreover, the epithelial-marker keratin 5 and mesenchymal marker Vimentin were co-expressed in the skin epidermis of mice with AD, suggesting the existence of hybrid epithelial-mesenchymal (E/M) cells possessing both epithelial and mesenchymal characteristics. In fact, we found that ΔNp63a, a stabilizing factor for hybrid E/M cells, was upregulated in the skin epidermis of the AD model mouse. Interestingly, increased expression of EMT markers was observed even at a nonlesion site in a patient with AD without initial inflammation or scratching. Therefore, EMT-like phenomena may occur independently of wound healing in skin of patients with AD.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139085744","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 Azalamellarin N as a Pyroptosis Inhibitor. 鉴定氮丙氨蝶呤 N 为一种裂解酶抑制剂

IF 2 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/bpb.b23-00569

Jun Takouda, Moeka Nakamura, Akane Murasaki, Waka Shimosako, Aoi Hidaka, Shino Honda, Susumu Tanimura, Fumito Ishibashi, Norihiko Kawasaki, Jun Ishihara, Tsutomu Fukuda, Kohsuke Takeda

{"title":"Identification of Azalamellarin N as a Pyroptosis Inhibitor.","authors":"Jun Takouda, Moeka Nakamura, Akane Murasaki, Waka Shimosako, Aoi Hidaka, Shino Honda, Susumu Tanimura, Fumito Ishibashi, Norihiko Kawasaki, Jun Ishihara, Tsutomu Fukuda, Kohsuke Takeda","doi":"10.1248/bpb.b23-00569","DOIUrl":"10.1248/bpb.b23-00569","url":null,"abstract":"Pyroptosis is a form of regulated cell death that promotes inflammation; it attracts much attention because its dysregulation leads to various inflammatory diseases. To help explore the precise mechanisms by which pyroptosis is regulated, in this study, we searched for chemical compounds that inhibit pyroptosis. From our original compound library, we identified azalamellarin N (AZL-N), a hexacyclic pyrrole alkaloid, as an inhibitor of pyroptosis induced by R837 (also called imiquimod), which is an agonist of the intracellular multiprotein complex nucleotide-binding and oligomerization domain-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome. However, whereas the effect of AZL-N on R837-induced pyroptosis was relatively weak, AZL-N strongly inhibited pyroptosis induced by extracellular ATP or nigericin, which are different types of NLRP3 inflammasome agonists. This was in contrast with the results that MCC950, a well-established NLRP3 inhibitor, consistently inhibited pyroptosis irrespective of the type of stimulus. We also found that AZL-N inhibited activation of caspase-1 and apoptosis-associated speck-like proteins containing a caspase activation and recruitment domain (ASC), which are components of the NLRP3 inflammasome. Analysis of the structure-activity relationship revealed that a lactam ring of AZL-N, which has been shown to contribute to the strong binding of AZL-N to its known target protein kinases, is required for its inhibitory effects on pyroptosis. These results suggest that AZL-N inhibits pyroptosis by targeting molecule(s), which may be protein kinase(s), that act upstream of NLRP3 inflammasome activation, rather than by directly targeting the components of the NLRP3 inflammasome. Further identification and analysis of target molecule(s) of AZL-N will shed light on the regulatory mechanisms of pyroptosis, particularly those depending on proinflammatory stimuli.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139085746","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

New Maintenance Culture Method for Intestinal Stem Cells Derived from Human Induced Pluripotent Stem Cells. 从人类诱导多能干细胞中提取的肠干细胞的新型维持培养方法。

IF 2 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/bpb.b23-00573

Shota Mizuno, Yumi Jinnoh, Ayaka Arita, Shimeng Qiu, Tadahiro Hashita, Eisei Hori, Takahiro Iwao, Tamihide Matsunaga

{"title":"New Maintenance Culture Method for Intestinal Stem Cells Derived from Human Induced Pluripotent Stem Cells.","authors":"Shota Mizuno, Yumi Jinnoh, Ayaka Arita, Shimeng Qiu, Tadahiro Hashita, Eisei Hori, Takahiro Iwao, Tamihide Matsunaga","doi":"10.1248/bpb.b23-00573","DOIUrl":"10.1248/bpb.b23-00573","url":null,"abstract":"Most orally administered drugs exert their effects after being absorbed in the small intestine. Therefore, new drugs must undergo nonclinical pharmacokinetic evaluations in the small intestine. Enterocytes derived from human induced pluripotent stem cells (hiPSCs) are expected to be used in the evaluation system, as they reflect human intestinal characteristics more accurately; moreover, several differentiation protocols are available for these cells. However, enterocytes derived from hiPSCs have drawbacks such as time, cost, and lot-to-lot differences. Hence, to address these issues, we attempted to maintain hiPSC-derived intestinal stem cells (ISCs) that can differentiate into various intestinal cells by regulating various pathways. Although our previous attempt was partly successful, the drawbacks of elevated cost and complicated handling remained, because more than 10 factors (A 83-01, CHIR99021, epidermal growth factor, basic fibroblast growth factor, SB202190, nicotinamide, N-acetylcysteine, valproic acid, Wnt3a, R-spondin 1, and noggin) are needed to maintain ISCs. Therefore, in this study, we successfully maintained ISCs using only five factors, including growth factors. Moreover, we generated not only enterocytes but also intestinal organoids from the maintained ISCs. Thus, our novel findings provided a time-saving and cost-effective culture method for enterocytes derived from hiPSCs.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139085748","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

Oleic Acid Activates Mitochondrial Energy Metabolism and Reduces Oxidative Stress Resistance in the Pancreatic β-Cell Line INS-1. 油酸激活线粒体能量代谢并降低胰腺β细胞株INS-1的氧化应激抵抗力

IF 2 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/bpb.b23-00559

Mariko Suzuki, Kaoruko Endo, Riko Nagata, Naoko Iida-Tanaka

{"title":"Oleic Acid Activates Mitochondrial Energy Metabolism and Reduces Oxidative Stress Resistance in the Pancreatic β-Cell Line INS-1.","authors":"Mariko Suzuki, Kaoruko Endo, Riko Nagata, Naoko Iida-Tanaka","doi":"10.1248/bpb.b23-00559","DOIUrl":"10.1248/bpb.b23-00559","url":null,"abstract":"Elevated concentration of saturated fatty acids in plasma adversely affects pancreatic β-cells, but the effects of unsaturated fatty acids are controversial. In this study, we examined the effects of oleic acid (OA), a monounsaturated fatty acid, on mitochondrial function, which is important for insulin secretion, using INS-1 cells, a pancreatic β-cell line derived from rats. Observations of mitochondrial membrane potential and intracellular ATP concentration showed that the electron transport chain was enhanced and ATP production increased in cells treated with OA, indicating that the response that occurs from sensing an increase in glucose concentration to the production of ATP was accelerated. Measurements of intracellular reactive oxygen species (ROS) indicated that the rate of increase in ROS after glucose stimulation was significantly higher in OA-treated cells. The mRNA expression levels of superoxide dismutase 1 and 2, which are responsive to ROS and other substances, were significantly increased in OA 1-d treated cells, but decreased in OA 7-d treated cells. It can be inferred that continued exposure to high concentrations of OA reduced ROS processing capacity and increased intracellular ROS levels. The mRNA expression of apoptosis-inducing enzyme Caspase-3 was significantly increased in OA-treated cells, although its activity was not high. However, the apoptosis induction rate after H2O2 stimulation was significantly higher in OA-treated cells. The high OA environment was shown to promote mitochondrial energy metabolism, leading to an increase in glucose sensitivity and a decrease in oxidative stress resistance.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139085749","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