Journal of pharmacological sciences最新文献_第10页

Neuronal activation of nucleus accumbens by local methamphetamine administration induces cognitive impairment through microglial inflammation in mice 小鼠局部注射甲基苯丙胺激活伏隔核的神经元，通过小胶质细胞炎症诱发认知障碍

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2024-01-09 DOI: 10.1016/j.jphs.2023.12.003

Yuka Kusui, Naotaka Izuo, Reika Tokuhara, Takashi Asano, Atsumi Nitta

{"title":"Neuronal activation of nucleus accumbens by local methamphetamine administration induces cognitive impairment through microglial inflammation in mice","authors":"Yuka Kusui, Naotaka Izuo, Reika Tokuhara, Takashi Asano, Atsumi Nitta","doi":"10.1016/j.jphs.2023.12.003","DOIUrl":"10.1016/j.jphs.2023.12.003","url":null,"abstract":"<div><p>More than half of methamphetamine (METH) users present with cognitive impairment, making it difficult for them to reintegrate into society. However, the mechanisms of METH-induced cognitive impairment remain unclear. METH causes neuronal hyperactivation in the nucleus accumbens (NAc) by aberrantly releasing dopamine, which triggers dependence. In this study, to clarify the involvement of hyperactivation of NAc in METH-induced cognitive impairment, mice were locally microinjected with METH into NAc (mice with METH (NAc)) and investigated their cognitive phenotype. Mice with METH (NAc) exhibited cognitive dysfunction in behavioral analyses and decreased long-term potentiation in the hippocampus, with NAc activation confirmed by expression of FosB, a neuronal activity marker. In the hippocampus of mice with METH (NAc), activated microglia, but not astroglia, and upregulated microglia-related genes, <em>Il1b</em> and <em>C1qa</em> were observed. Finally, administration of minocycline, a tetracycline antibiotic with suppressive effect on microglial activation, to mice with METH (NAc) ameliorated cognitive impairment and synaptic dysfunction by suppressing the increased expression of <em>Il1b</em> and <em>C1qa</em> in the hippocampus. In conclusion, activation of NAc by injection of METH into NAc elicited cognitive impairment by facilitating immune activation in mice. This study suggests that immunological intervention could be a therapeutic strategy for addiction-related cognitive disturbances.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"154 3","pages":"Pages 127-138"},"PeriodicalIF":3.5,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861323000713/pdfft?md5=d95bb2fc4d25ec32212485dec23607e7&pid=1-s2.0-S1347861323000713-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139414616","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

Blockade of vasoactive intestinal peptide receptor 2 (VIPR2) signaling suppresses cyclin D1-dependent cell-cycle progression in MCF-7 cells 阻断血管活性肠肽受体 2 (VIPR2) 信号传导可抑制 MCF-7 细胞中依赖细胞周期蛋白 D1 的细胞周期进程

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2024-01-05 DOI: 10.1016/j.jphs.2024.01.002

Satoshi Asano , Ami Ono , Kaede Baba , Teru Uehara , Kotaro Sakamoto , Atsuko Hayata-Takano , Takanobu Nakazawa , Souichi Yanamoto , Kotaro Tanimoto , Hitoshi Hashimoto , Yukio Ago

{"title":"Blockade of vasoactive intestinal peptide receptor 2 (VIPR2) signaling suppresses cyclin D1-dependent cell-cycle progression in MCF-7 cells","authors":"Satoshi Asano , Ami Ono , Kaede Baba , Teru Uehara , Kotaro Sakamoto , Atsuko Hayata-Takano , Takanobu Nakazawa , Souichi Yanamoto , Kotaro Tanimoto , Hitoshi Hashimoto , Yukio Ago","doi":"10.1016/j.jphs.2024.01.002","DOIUrl":"10.1016/j.jphs.2024.01.002","url":null,"abstract":"<div><p>Vasoactive intestinal peptide (VIP) receptor 2 (VIPR2) is a G protein-coupled receptor that binds to Gαs, Gαi, and Gαq proteins to regulate various downstream signaling molecules, such as protein kinase A (PKA), phosphatidylinositol 3-kinase (PI3K), and phospholipase C. In this study, we examined the role of VIPR2 in cell cycle progression. KS-133, a newly developed VIPR2-selective antagonist peptide, attenuated VIP-induced cell proliferation in MCF-7 cells. The percentage of cells in the S-M phase was decreased in MCF-7 cells treated with KS-133. KS-133 in the presence of VIP decreased the phosphorylation of extracellular signal-regulated kinase (ERK), AKT, and glycogen synthase kinase-3β (GSK3β), resulting in a decrease in cyclin D1 levels. In MCF-7 cells stably-expressing VIPR2, KS-133 decreased PI3K activity and cAMP levels. Treatment with the ERK-specific kinase (MEK) inhibitor U0126 and the class I PI3K inhibitor ZSTK474 decreased the percentage of cells in the S phase. KS-133 reduced the percentage of cells in the S phase more than treatment with U0126 or ZSTK474 alone and did not affect the effect of the mixture of these inhibitors. Our findings suggest that VIPR2 signaling regulates cyclin D1 levels through the cAMP/PKA/ERK and PI3K/AKT/GSK3β pathways, and mediates the G1/S transition to control cell proliferation.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"154 3","pages":"Pages 139-147"},"PeriodicalIF":3.5,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000021/pdfft?md5=d75ede11b499c701adc03b6494bc3efd&pid=1-s2.0-S1347861324000021-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139102169","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

The role of P2Y6 receptor in the pathogenesis of cardiovascular and inflammatory diseases P2Y6 受体在心血管疾病和炎症性疾病发病机制中的作用

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2024-01-05 DOI: 10.1016/j.jphs.2024.01.003

Kazuhiro Nishiyama

{"title":"The role of P2Y6 receptor in the pathogenesis of cardiovascular and inflammatory diseases","authors":"Kazuhiro Nishiyama","doi":"10.1016/j.jphs.2024.01.003","DOIUrl":"10.1016/j.jphs.2024.01.003","url":null,"abstract":"<div><p>The purinergic receptor P2Y<sub>6</sub> receptor (P2Y<sub>6</sub>R) is a member of the G protein-coupled receptors (GPCR) family. P2Y<sub>6</sub>R is widely expressed in various cell types and plays a critical role in physiological processes, where it is activated by extracellular uridine diphosphate (UDP) and mobilizes Ca<sup>2+</sup> via the G<sub>αq/11</sub> protein pathway. We have recently discovered the pathophysiological role of P2Y<sub>6</sub>R in cardiovascular and inflammatory diseases, including inflammatory bowel disease and non-alcoholic fatty liver disease. Furthermore, we uncovered the redox-dependent internalization of P2Y<sub>6</sub>R. In this review, we provide a comprehensive overview of the pathophysiological activity of P2Y<sub>6</sub>R in cardiovascular and inflammatory diseases. Additionally, we discuss the concept of atypical internalization control of GPCRs, which may be applied in the prevention and treatment of intestinal inflammation and cardiovascular remodeling.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"154 2","pages":"Pages 108-112"},"PeriodicalIF":3.5,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000033/pdfft?md5=247fd27157e9f44c7eecbc02e15a9785&pid=1-s2.0-S1347861324000033-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139102719","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

2,5-Dimethyl-celecoxib induces early termination of inflammatory responses by transient macrophage accumulation and inhibits the progression of cardiac remodeling in a mouse model of cryoinjury-induced myocardial infarction 在冷冻损伤诱发心肌梗死的小鼠模型中，2,5-二甲基-塞来昔布通过短暂的巨噬细胞聚集诱导炎症反应的早期终止，并抑制心脏重塑的进展

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2024-01-03 DOI: 10.1016/j.jphs.2024.01.001

Takehiro Kishigami , Shin Ishikane , Masaki Arioka , Kazunobu Igawa , Yosuke Nishimura , Fumi Takahashi-Yanaga

{"title":"2,5-Dimethyl-celecoxib induces early termination of inflammatory responses by transient macrophage accumulation and inhibits the progression of cardiac remodeling in a mouse model of cryoinjury-induced myocardial infarction","authors":"Takehiro Kishigami , Shin Ishikane , Masaki Arioka , Kazunobu Igawa , Yosuke Nishimura , Fumi Takahashi-Yanaga","doi":"10.1016/j.jphs.2024.01.001","DOIUrl":"10.1016/j.jphs.2024.01.001","url":null,"abstract":"<div><p>In our previous study, we reported that 2, 5-dimethyl-celecoxib (DM-C), a derivative of celecoxib, prevents cardiac remodeling in different mouse models of heart failure, including myocardial infarction (MI). The inflammatory response after MI affects the progression of cardiac remodeling, wherein the immune cells, mainly macrophages, play crucial roles. Therefore, we evaluated the effect of DM-C on macrophages in a cryoinjury-induced myocardial infarction (CMI) mouse model. We observed that DM-C attenuated the deterioration of left ventricular ejection fraction and cardiac fibrosis 14 d after CMI. Gene expression of pro-inflammatory cytokines at the infarct site was reduced by DM-C treatment. Analysis of macrophage surface antigens revealed that DM-C induced transient accumulation of macrophages at the infarct site without affecting their polarization. <em>In vitro</em> experiments using peritoneal monocytes/macrophages revealed that DM-C did not directly increase the phagocytic ability of the macrophages but increased their number, thereby upregulating the clearance capacity. Moreover, DM-C rapidly excluded the cells expressing necrotic cell marker from the infarct site. These results suggested that DM-C enhanced the clearance capacity of macrophages by transiently increasing their number at the infarct site, and terminated the escape from the inflammatory phase earlier, thereby suppressing excessive cardiac remodeling and ameliorating cardiac dysfunction.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"154 2","pages":"Pages 97-107"},"PeriodicalIF":3.5,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S134786132400001X/pdfft?md5=82cda8a4705268743df7a4dd30cfe1b9&pid=1-s2.0-S134786132400001X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139102165","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

Farrerol suppresses osteoclast differentiation and postmenopausal osteoporosis by inhibiting the nuclear factor kappa B signaling pathway 法瑞罗通过抑制核因子卡巴B信号通路抑制破骨细胞分化和绝经后骨质疏松症

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2023-12-29 DOI: 10.1016/j.jphs.2023.12.011

Wei Lu , Guobin Qi , Xiuying Yang , Defang Li , Weibin Chen , Qingmin Zeng , Zengxin Jiang

{"title":"Farrerol suppresses osteoclast differentiation and postmenopausal osteoporosis by inhibiting the nuclear factor kappa B signaling pathway","authors":"Wei Lu , Guobin Qi , Xiuying Yang , Defang Li , Weibin Chen , Qingmin Zeng , Zengxin Jiang","doi":"10.1016/j.jphs.2023.12.011","DOIUrl":"10.1016/j.jphs.2023.12.011","url":null,"abstract":"<div><p>Excessive bone resorption caused by upregulated osteoclast activity is a key factor in osteoporosis pathogenesis. Farrerol is a typical natural flavanone and exhibits various pharmacological actions. However, the role and mechanism of action of farrerol in osteoclast differentiation regulation remain unclear. This study aimed to evaluate the effects and mechanism of farrerol on the inhibition of osteoclastogenesis. Tartrate-resistant acid phosphatase staining, F-actin staining, and the pit formation assay were performed to examine the differentiation and functions of osteoclasts <em>in vitro</em>. The expression of proteins associated with the nuclear factor kappa B and mitogen-activated protein kinase signaling pathways was analyzed by western blotting. Dual X-ray absorptiometry, microcomputed tomography, and histopathological and immunohistochemical analyses were performed to determine the therapeutic effect of farrerol in vivo bone loss prevention. The effects of farrerol on osteoblastic bone formation were assessed using alkaline phosphatase, alizarin red S staining, and calcein-alizarin red S double labeling. Farrerol inhibited osteoclastogenesis and bone resorption in osteoclasts by suppressing nuclear factor kappa B signaling rather than mitogen-activated protein kinase signaling <em>in vitro</em>. Farrerol protected mice against ovariectomy-induced bone loss by inhibiting osteoclast-mediated bone resorption, instead of promoting osteoblast-mediated bone formation <em>in vivo</em>. The findings of the current study revealed that farrerol is a potential therapeutic agent for osteoporosis.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"154 2","pages":"Pages 113-126"},"PeriodicalIF":3.5,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861323000798/pdfft?md5=c82522de9fc6e56ef755916fe16cfcf7&pid=1-s2.0-S1347861323000798-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139064025","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

Attenuation of protein arginine dimethylation via S-nitrosylation of protein arginine methyltransferase 1 通过 S-亚硝基化蛋白质精氨酸甲基转移酶 1 减弱蛋白质精氨酸二甲基化

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2023-12-28 DOI: 10.1016/j.jphs.2023.12.012

Rikako Taniguchi , Yuto Moriya , Naoshi Dohmae , Takehiro Suzuki , Kengo Nakahara , Sho Kubota , Nobumasa Takasugi , Takashi Uehara

{"title":"Attenuation of protein arginine dimethylation via S-nitrosylation of protein arginine methyltransferase 1","authors":"Rikako Taniguchi , Yuto Moriya , Naoshi Dohmae , Takehiro Suzuki , Kengo Nakahara , Sho Kubota , Nobumasa Takasugi , Takashi Uehara","doi":"10.1016/j.jphs.2023.12.012","DOIUrl":"10.1016/j.jphs.2023.12.012","url":null,"abstract":"<div><p>Upregulation of nitric oxide (NO) production contributes to the pathogenesis of numerous diseases via <em>S</em>-nitrosylation, a post-translational modification of proteins. This process occurs due to the oxidative reaction between NO and a cysteine thiol group; however, the extent of this reaction remains unknown. <em>S</em>-Nitrosylation of PRMT1, a major asymmetric arginine methyltransferase of histones and numerous RNA metabolic proteins, was induced by NO donor treatment. We found that nitrosative stress leads to <em>S</em>-nitrosylation of cysteine 119, located near the active site, and attenuates the enzymatic activity of PRMT1. Interestingly, RNA sequencing analysis revealed similarities in the changes in expression elicited by NO and PRMT1 inhibitors or knockdown. A comprehensive search for PRMT1 substrates using the proximity-dependent biotin identification method highlighted many known and new substrates, including RNA-metabolizing enzymes. To validate this result, we selected the RNA helicase DDX3 and demonstrated that arginine methylation of DDX3 is induced by PRMT1 and attenuated by NO treatment. Our results suggest the existence of a novel regulatory system associated with transcription and RNA metabolism via protein <em>S</em>-nitrosylation.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"154 3","pages":"Pages 209-217"},"PeriodicalIF":3.5,"publicationDate":"2023-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861323000804/pdfft?md5=7fef0647d8a7b34f67165cac0c07fe9c&pid=1-s2.0-S1347861323000804-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139064068","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

Taurine deficiency associated with dilated cardiomyopathy and aging 牛磺酸缺乏与扩张型心肌病和衰老有关

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2023-12-28 DOI: 10.1016/j.jphs.2023.12.006

Takashi Ito , Shigeru Murakami

{"title":"Taurine deficiency associated with dilated cardiomyopathy and aging","authors":"Takashi Ito , Shigeru Murakami","doi":"10.1016/j.jphs.2023.12.006","DOIUrl":"10.1016/j.jphs.2023.12.006","url":null,"abstract":"<div><p>Taurine (2-aminoethanesulfonic acid) is a free amino acid found ubiquitously and abundantly in mammalian tissues. Taurine content in the heart is approximately 20 mM, which is approximately 100 times higher than plasma concentration. The high intracellular concentration of taurine is maintained by the taurine transporter (TauT; Slc6a6). Taurine plays various roles, including the regulation of intracellular ion dynamics, calcium handling, and acting as an antioxidant in the heart. Some species, such as cats and foxes, have low taurine biosynthetic capacity, and dietary taurine deficiency can lead to disorders such as dilated cardiomyopathy and blindness. In humans, the relationship between dietary taurine deficiency and cardiomyopathy is not yet clear, but a genetic mutation related to the taurine transporter has been reported to be associated with dilated cardiomyopathy. On the other hand, many studies have shown an association between dietary taurine intake and age-related diseases. Notably, it has recently been reported that taurine declines with age and is associated with lifespan in worms and mice, as well as healthspan in mice and monkeys. In this review, we summarize the role of dietary and genetic taurine deficiency in the development of cardiomyopathy and aging.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"154 3","pages":"Pages 175-181"},"PeriodicalIF":3.5,"publicationDate":"2023-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861323000749/pdfft?md5=641c4731cf58f460278da1383b0d2915&pid=1-s2.0-S1347861323000749-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139064150","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

Mechanism of cytotoxicity induced by the cigarette smoke extract (CSE) of heated tobacco products in vascular smooth muscle cells: A comparative study of the cytotoxic effects of CSE and the ferroptosis inducer, erastin 加热烟草制品的香烟烟雾提取物（CSE）在血管平滑肌细胞中诱导细胞毒性的机制：烟草烟雾提取物与铁变态反应诱导剂麦拉宁的细胞毒性作用比较研究

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2023-12-27 DOI: 10.1016/j.jphs.2023.12.010

Takahiro Horinouchi , Yuichi Mazaki , Soichi Miwa

{"title":"Mechanism of cytotoxicity induced by the cigarette smoke extract (CSE) of heated tobacco products in vascular smooth muscle cells: A comparative study of the cytotoxic effects of CSE and the ferroptosis inducer, erastin","authors":"Takahiro Horinouchi , Yuichi Mazaki , Soichi Miwa","doi":"10.1016/j.jphs.2023.12.010","DOIUrl":"10.1016/j.jphs.2023.12.010","url":null,"abstract":"<div><p>Heated tobacco products (HTPs) are marketed worldwide as less harmful alternatives to combustible cigarettes; however, their cytotoxic mechanisms in vascular smooth muscle cells are poorly understood. Ferroptosis is defined as iron-dependent cell death caused by the accumulation of lipid peroxidation products. In this study, the cytotoxic effects of nicotine- and tar-free cigarette smoke extracts (CSE) derived from three types of HTPs and the ferroptosis inducer, erastin, on vascular smooth muscle A7r5 cells were compared. Cigarette smoke from all HTPs was generated according to the following puffing regime: 55 mL, puff volume; 30 s, puff interval; 2 s, puff duration; bell-shaped, puff profile; and no blocking of the ventilation holes. Erastin and CSE decreased mitochondrial metabolic activity and increased lactate dehydrogenase leakage. The cytotoxic effects of erastin were almost completely inhibited by the radical-trapping antioxidant, UAMC-3203; iron chelator, deferoxamine mesylate (DFO); 12/15-lipoxygenase (12/15-LOX) inhibitor, baicalein; and selective 15-LOX inhibitor, ML351. In contrast, CSE-induced cell damage was partially attenuated by UAMC-3203, baicalein, and ML351 but not by DFO. These results suggest that erastin induces ferroptosis via 15-LOX-mediated iron-dependent lipid peroxidation, whereas CSE causes iron-independent cell damage via 15-LOX-mediated lipid peroxidation-dependent and -independent mechanisms.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"154 2","pages":"Pages 86-96"},"PeriodicalIF":3.5,"publicationDate":"2023-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861323000786/pdfft?md5=26bf9b4bd7222688421b2adaa2ebaa34&pid=1-s2.0-S1347861323000786-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139064398","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

Supersulfide prevents cigarette smoke extract-induced mitochondria hyperfission and cardiomyocyte early senescence by inhibiting Drp1-filamin complex formation 超硫化物通过抑制 Drp1--维生素复合物的形成，防止香烟烟雾提取物诱导的线粒体过度分裂和心肌细胞早期衰老

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2023-12-27 DOI: 10.1016/j.jphs.2023.12.008

Akiyuki Nishimura , Liuchenzi Zhou , Yuri Kato , Xinya Mi , Tomoya Ito , Yuko Ibuki , Yasunari Kanda , Motohiro Nishida

{"title":"Supersulfide prevents cigarette smoke extract-induced mitochondria hyperfission and cardiomyocyte early senescence by inhibiting Drp1-filamin complex formation","authors":"Akiyuki Nishimura , Liuchenzi Zhou , Yuri Kato , Xinya Mi , Tomoya Ito , Yuko Ibuki , Yasunari Kanda , Motohiro Nishida","doi":"10.1016/j.jphs.2023.12.008","DOIUrl":"10.1016/j.jphs.2023.12.008","url":null,"abstract":"<div><p>Smoking is one of the most serious risk factors for cardiovascular diseases. Although cigarette mainstream and sidestream smoke are significant contributors to increased cardiovascular mortality and morbidity, the underlying mechanism is still unclear. Here, we report that exposure of rat neonatal cardiomyocytes to cigarette smoke extract (CSE) induces mitochondrial hyperfission-mediated myocardial senescence. CSE leads to mitochondrial fission and reactive oxygen species (ROS) production through the complex formation between mitochondrial fission factor Drp1 and actin-binding protein, filamin A. Pharmacological perturbation of interaction between Drp1 and filamin A by cilnidipine and gene knockdown of Drp1 or filamin A inhibited CSE-induced mitochondrial hyperfission and ROS production as well as myocardial senescence. We previously reported that Drp1 activity is controlled by supersulfide-induced Cys644 polysulfidation. The redox-sensitive Cys644 was critical for CSE-mediated interaction with filamin A. The administration of supersulfide donor, Na<sub>2</sub>S<sub>3</sub> also improved mitochondrial hyperfission-mediated myocardial senescence induced by CSE. Our results suggest the important role of Drp1-filamin A complex formation on cigarette smoke-mediated cardiac risk and the contribution of supersulfide to mitochondrial fission-associated myocardial senescence.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"154 2","pages":"Pages 127-135"},"PeriodicalIF":3.5,"publicationDate":"2023-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861323000762/pdfft?md5=f18b81002348c43b61b1127c7a99c095&pid=1-s2.0-S1347861323000762-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139064027","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

CU06-1004 alleviates oxidative stress and inflammation on folic acid-induced acute kidney injury in mice CU06-1004 可减轻氧化应激和炎症对叶酸诱导的小鼠急性肾损伤的影响

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2023-12-23 DOI: 10.1016/j.jphs.2023.12.009

Cho-Rong Bae , Yeomyeong Kim , Young-Guen Kwon

{"title":"CU06-1004 alleviates oxidative stress and inflammation on folic acid-induced acute kidney injury in mice","authors":"Cho-Rong Bae , Yeomyeong Kim , Young-Guen Kwon","doi":"10.1016/j.jphs.2023.12.009","DOIUrl":"10.1016/j.jphs.2023.12.009","url":null,"abstract":"<div><h3>Purpose</h3><p>Acute kidney injury (AKI) is characterized by reduced renal function, oxidative stress, inflammation, and renal fibrosis. CU06-1004, an endothelial cell dysfunction blocker, exhibits anti-inflammatory effects by reducing vascular permeability in pathological conditions. However, the potential effects of CU06-1004 on AKI have not been investigated. We investigated the renoprotective effect of CU06-1004 against oxidative stress, inflammation, and fibrotic changes in a folic acid-induced AKI model.</p></div><div><h3>Methods</h3><p>AKI was induced by intraperitoneal injection of high dose (250 mg/kg) folic acid in mice. CU06-1004 was orally administered a low (10 mg/kg) or high dose (20 mg/kg).</p></div><div><h3>Results</h3><p>CU06-1004 ameliorated folic acid-induced AKI by decreasing serum blood urea nitrogen and creatinine levels, mitigating histological abnormalities, and decreasing tubular injury markers such as kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin in folic acid-induced AKI mice. Additionally, CU06-1004 alleviated folic acid-induced oxidative stress by reducing 4-hydroxynonenal and malondialdehyde levels. Furthermore, it attenuated macrophage infiltration and suppressed the expression of the proinflammatory factors, including tumor necrosis factor-α, intercellular adhesion molecule-1, and vascular cell adhesion protein-1. Moreover, CU06-1004 mitigated folic acid-induced tubulointerstitial fibrosis by decreasing α-smooth muscle actin and transforming growth factor-β expression.</p></div><div><h3>Conclusion</h3><p>These findings suggest CU06-1004 as a potential therapeutic agent for folic acid-induced AKI.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"154 2","pages":"Pages 77-85"},"PeriodicalIF":3.5,"publicationDate":"2023-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861323000774/pdfft?md5=d65f6766ca672922acb3e56e1e5331e8&pid=1-s2.0-S1347861323000774-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139027988","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}

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