Journal of pharmacological sciences最新文献_第10页

Proteasome inhibitors induce apoptosis by superoxide anion generation via NADPH oxidase 5 in human neuroblastoma SH-SY5Y cells 蛋白酶体抑制剂通过 NADPH 氧化酶 5 在人神经母细胞瘤 SH-SY5Y 细胞中生成超氧阴离子诱导细胞凋亡

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2024-03-27 DOI: 10.1016/j.jphs.2024.03.002

Akiko Yamamuro-Tanabe, Yu Oshima, Takumi Iyama, Yuki Ishimaru, Yasuhiro Yoshioka

{"title":"Proteasome inhibitors induce apoptosis by superoxide anion generation via NADPH oxidase 5 in human neuroblastoma SH-SY5Y cells","authors":"Akiko Yamamuro-Tanabe, Yu Oshima, Takumi Iyama, Yuki Ishimaru, Yasuhiro Yoshioka","doi":"10.1016/j.jphs.2024.03.002","DOIUrl":"https://doi.org/10.1016/j.jphs.2024.03.002","url":null,"abstract":"<div><p>The ubiquitin-proteasome system (UPS) is a major proteolytic system that plays an important role in the regulation of various cell processes, such as cell cycle, stress response, and transcriptional regulation, especially in neurons, and dysfunction of UPS is considered to be a cause of neuronal cell death in neurodegenerative diseases. However, the mechanism of neuronal cell death caused by UPS dysfunction has not yet been fully elucidated.</p><p>In this study, we investigated the mechanism of neuronal cell death induced by proteasome inhibitors using human neuroblastoma SH-SY5Y cells. Z-Leu-D-Leu-Leu-al (MG132), a proteasome inhibitor, induced apoptosis in SH-SY5Y cells in a concentration- and time-dependent manner. Antioxidants N-acetylcysteine and EUK-8 attenuated MG132-induced apoptosis. Apocynin and diphenyleneiodonium, inhibitors of NADPH oxidase (NOX), an enzyme that produces superoxide anions, also attenuated MG132-induced apoptosis. It was also found that MG132 treatment increased the expression of NOX5, a NOX family member, and that siRNA-mediated silencing of NOX5 and BAPTA-AM, which inhibits NOX5 by chelating calcium, suppressed MG132-induced apoptosis and production of reactive oxygen species in SH-SY5Y cells.</p><p>These results suggest that MG132 induces apoptosis in SH-SY5Y cells through the production of superoxide anion by NOX5.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"155 2","pages":"Pages 52-62"},"PeriodicalIF":3.5,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000288/pdfft?md5=b628cb33348109571b1bba490c2d7965&pid=1-s2.0-S1347861324000288-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140351934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CSF1R inhibitor PLX3397 depletes microglia in Mongolian gerbil Meriones unguiculatus, but not in syrian hamster Mesocricetus auratus CSF1R 抑制剂 PLX3397 可消耗蒙古沙鼠的小胶质细胞，但不会消耗叙利亚仓鼠的小胶质细胞

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2024-03-23 DOI: 10.1016/j.jphs.2024.03.003

Ren Y. Sato, Yumin Zhang , Koki T. Kotake , Hiraku Onishi, Shiho Ito, Hiroaki Norimoto, Zhiwen Zhou

{"title":"CSF1R inhibitor PLX3397 depletes microglia in Mongolian gerbil Meriones unguiculatus, but not in syrian hamster Mesocricetus auratus","authors":"Ren Y. Sato, Yumin Zhang , Koki T. Kotake , Hiraku Onishi, Shiho Ito, Hiroaki Norimoto, Zhiwen Zhou","doi":"10.1016/j.jphs.2024.03.003","DOIUrl":"10.1016/j.jphs.2024.03.003","url":null,"abstract":"<div><p>Microglia are the residential immune cells in the central nervous system. Their roles as innate immune cells and regulators of synaptic remodeling are critical to the development and the maintenance of the brain. Numerous studies have depleted microglia to elucidate their involvement in healthy and pathological conditions. PLX3397, a blocker of colony stimulating factor 1 receptor (CSF1R), is widely used to deplete mouse microglia due to its non-invasiveness and convenience. Recently, other small rodents, including Syrian hamsters (<em>Mesocricetus auratus</em>) and Mongolian gerbils (<em>Meriones unguiculatus</em>), have been recognized as valuable animal models for studying brain functions and diseases. However, whether microglia depletion via PLX3397 is feasible in these species remains unclear. Here, we administered PLX3397 orally via food pellets to hamsters and gerbils. PLX3397 successfully depleted gerbil microglia but had no effect on microglial density in hamsters. Comparative analysis of the CSF1R amino acid sequence in different species hints that amino acid substitutions in the juxtamembrane domain may potentially contribute to the inefficacy of PLX3397 in hamsters.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"155 2","pages":"Pages 29-34"},"PeriodicalIF":3.5,"publicationDate":"2024-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S134786132400029X/pdfft?md5=adbf8b5c2390572036d58aeb3338ba59&pid=1-s2.0-S134786132400029X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140273890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Upregulation of ATF4 mediates the cellular adaptation to pharmacologic inhibition of amino acid transporter LAT1 in pancreatic ductal adenocarcinoma cells ATF4 的上调介导了胰腺导管腺癌细胞对氨基酸转运体 LAT1 药物抑制的适应性变化

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2024-03-13 DOI: 10.1016/j.jphs.2024.03.001

Yu Ma , Suguru Okuda , Hiroki Okanishi , Minhui Xu , Chunhuan Jin , Hitoshi Endou , Ryuichi Ohgaki , Yoshikatsu Kanai

{"title":"Upregulation of ATF4 mediates the cellular adaptation to pharmacologic inhibition of amino acid transporter LAT1 in pancreatic ductal adenocarcinoma cells","authors":"Yu Ma , Suguru Okuda , Hiroki Okanishi , Minhui Xu , Chunhuan Jin , Hitoshi Endou , Ryuichi Ohgaki , Yoshikatsu Kanai","doi":"10.1016/j.jphs.2024.03.001","DOIUrl":"10.1016/j.jphs.2024.03.001","url":null,"abstract":"<div><p>L-type amino acid transporter 1 (LAT1) is recognized as a promising target for cancer therapy; however, the cellular adaptive response to its pharmacological inhibition remains largely unexplored. This study examined the adaptive response to LAT1 inhibition using nanvuranlat, a high-affinity LAT1 inhibitor. Proteomic analysis revealed the activation of a stress-induced transcription factor ATF4 following LAT1 inhibition, aligning with the known cellular responses to amino acid deprivation. This activation was linked to the GCN2-eIF2α pathway which regulates translation initiation. Our results show that ATF4 upregulation counteracts the suppressive effect of nanvuranlat on cell proliferation in pancreatic ductal adenocarcinoma cell lines, suggesting a role for ATF4 in cellular adaptation to LAT1 inhibition. Importantly, dual targeting of LAT1 and ATF4 exhibited more substantial anti-proliferative effects <em>in vitro</em> than individual treatments. This study underscores the potential of combining LAT1 and ATF4 inhibition as a therapeutic strategy in cancer treatment.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"155 1","pages":"Pages 14-20"},"PeriodicalIF":3.5,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000276/pdfft?md5=3ebaf9d7cc856ff4f50c85f1d9e44822&pid=1-s2.0-S1347861324000276-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140153095","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

Gallic acid ameliorates endometrial hyperplasia through the inhibition of the PI3K/AKT pathway and the down-regulation of cyclin D1 expression 没食子酸通过抑制 PI3K/AKT 通路和下调细胞周期蛋白 D1 的表达改善子宫内膜增生症

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2024-03-05 DOI: 10.1016/j.jphs.2024.02.015

Caijie Zheng , Yi Wang , Beilei Bi , Wencheng Zhou , Xinran Cao , Chenyang Zhang , Wentian Lu , Yang Sun , Jiao Qu , Wen Lv

{"title":"Gallic acid ameliorates endometrial hyperplasia through the inhibition of the PI3K/AKT pathway and the down-regulation of cyclin D1 expression","authors":"Caijie Zheng , Yi Wang , Beilei Bi , Wencheng Zhou , Xinran Cao , Chenyang Zhang , Wentian Lu , Yang Sun , Jiao Qu , Wen Lv","doi":"10.1016/j.jphs.2024.02.015","DOIUrl":"10.1016/j.jphs.2024.02.015","url":null,"abstract":"<div><h3>Background</h3><p>Gallic acid (GA) is an organic compound with phenolic properties that occurs naturally and can be found in Guizhi Fuling capsules, showcasing a wide range of biological functionalities.</p></div><div><h3>Purpose</h3><p>The objective of this study was to examine the influence of GA on endometrial hyperplasia (EH) and elucidate its underlying mechanism.</p></div><div><h3>Methods</h3><p>Initially, the induction of EH was achieved by administering estradiol to mice via continuous subcutaneous injection for a duration of 21 days. Concurrently, GA treatment was administered, and subsequently, the uterine tissue structure was assessed using hematoxylin and eosin (H&E) staining. Following this, the proliferation of human endometrial cells treated by GA was determined utilizing the CCK-8 method. Furthermore, network pharmacology and single-cell-RNA-seq data were employed to identify the target of GA action. In addition, we will employ immunofluorescence (IF), immunohistochemistry (IHC), flow cytometry, western blot and RT-qPCR methodologies to investigate the impact of GA on the expression level of cyclin D1, PI3K, p-PI3K, AKT, p-AKT.</p></div><div><h3>Results</h3><p>GA treatment ameliorated histopathological alterations in the uterus and suppress proliferation. Estradiol stimulation can activate the PI3K/AKT pathway, leading to up-regulation of cyclin D1 expression, whereas GA treatment results in down-regulation of its expression.</p></div><div><h3>Conclusions</h3><p>The expression of cyclin D1 is down-regulated by GA through the inhibition of the PI3K/AKT pathway, effectively mitigating estradiol-induced EH in mice.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"155 1","pages":"Pages 1-13"},"PeriodicalIF":3.5,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000264/pdfft?md5=420a84d4b79dcf40e2a866fa58bebee9&pid=1-s2.0-S1347861324000264-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140074878","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

Drug combination of topical ripasudil and brimonidine enhances neuroprotection in a mouse model of optic nerve injury 局部用瑞帕舒地尔和溴莫尼定联合用药可增强小鼠视神经损伤模型的神经保护作用

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2024-02-29 DOI: 10.1016/j.jphs.2024.02.011

Kazuhiko Namekata , Takahiko Noro , Euido Nishijima , Akiko Sotozono , Xiaoli Guo , Chikako Harada , Youichi Shinozaki , Yoshinori Mitamura , Tadashi Nakano , Takayuki Harada

{"title":"Drug combination of topical ripasudil and brimonidine enhances neuroprotection in a mouse model of optic nerve injury","authors":"Kazuhiko Namekata , Takahiko Noro , Euido Nishijima , Akiko Sotozono , Xiaoli Guo , Chikako Harada , Youichi Shinozaki , Yoshinori Mitamura , Tadashi Nakano , Takayuki Harada","doi":"10.1016/j.jphs.2024.02.011","DOIUrl":"10.1016/j.jphs.2024.02.011","url":null,"abstract":"<div><h3>Purpose</h3><p>To determine whether combination of topical ripasudil and brimonidine has more effective neuroprotection on retinal ganglion cells (RGCs) following injury to axons composing the optic nerve.</p></div><div><h3>Methods</h3><p>Topical ripasudil, brimonidine, or mixture of both drugs were administered to adult mice after optic nerve injury (ONI). The influence of drug conditions on RGC health were evaluated by the quantifications of surviving RGCs, phosphorylated p38 mitogen-activated protein kinase (phospho-p38), and expressions of trophic factors and proinflammatory mediators in the retina.</p></div><div><h3>Results</h3><p>Topical ripasudil and brimonidine suppressed ONI-induced RGC death respectively, and mixture of both drugs further stimulated RGC survival. Topical ripasudil and brimonidine suppressed ONI-induced phospho-p38 in the whole retina. In addition, topical ripasudil suppressed expression levels of TNFα, IL-1β and monocyte chemotactic protein-1 (MCP-1), whereas topical brimonidine increased the expression level of basic fibroblast growth factor (bFGF).</p></div><div><h3>Conclusions</h3><p>Combination of topical ripasudil and brimonidine may enhance RGC protection by modulating multiple signaling pathways in the retina.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"154 4","pages":"Pages 326-333"},"PeriodicalIF":3.5,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000227/pdfft?md5=ed158bb332fc314968c632e45fb88be8&pid=1-s2.0-S1347861324000227-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140011002","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

Laminar-selective spinal astrocyte population capable of converting tactile information into nociceptive in rats 能将大鼠触觉信息转化为痛觉信息的层状选择性脊髓星形胶质细胞群

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2024-02-27 DOI: 10.1016/j.jphs.2024.02.014

Daichi Sueto , Akihisa Onishi , Eriko I , Yu Yoshikawa , Makoto Tsuda

引用次数: 0

Icariin alleviates diabetic renal interstitial fibrosis aggravation by inhibiting miR-320a-3p targeting BMP6 淫羊藿苷通过抑制以 BMP6 为靶点的 miR-320a-3p 减轻糖尿病肾间质纤维化的恶化

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2024-02-27 DOI: 10.1016/j.jphs.2024.02.013

Kaiwei Wang , Mengjun Hou , Chen Qiao , Yalei Duan , Rongpin Tao , Xiniao Wang , Kang Xiao , Shuo Liu , Hanzhen Zhao , Jiali Wang , Zhirong Jia , Xuansheng Ding

{"title":"Icariin alleviates diabetic renal interstitial fibrosis aggravation by inhibiting miR-320a-3p targeting BMP6","authors":"Kaiwei Wang , Mengjun Hou , Chen Qiao , Yalei Duan , Rongpin Tao , Xiniao Wang , Kang Xiao , Shuo Liu , Hanzhen Zhao , Jiali Wang , Zhirong Jia , Xuansheng Ding","doi":"10.1016/j.jphs.2024.02.013","DOIUrl":"10.1016/j.jphs.2024.02.013","url":null,"abstract":"<div><p>Diabetic nephropathy is a common complication of diabetes, accumulating evidence underscores the pivotal role of tubulointerstitial fibrosis in the progression of diabetic nephropathy. However, the underlying mechanisms remain incompletely understood. Although the mechanisms in diabetic nephropathy fibrosis have been the focus of many studies, only limited information is currently available concerning microRNA regulation in tubulointerstitial fibrosis. In this study, we aimed to investigate the roles of miR-320a-3p and bone morphogenetic protein-6 (BMP6) in tubulointerstitial fibrosis. After inducing fibrosis with high glucose in HK-2 cells, we found that miR-320a-3p is significantly up-regulated, whereas BMP6 is markedly down-regulated. These changes suggest close link between miR-320a-3p and BMP6 in tubulointerstitial fibrosis. To elucidate this phenomenon, miR-320a-3p mimic, inhibitor and siBMP6 were employed. We observed in miR-320a-3p mimic group the fibrosis marker include alpha smooth muscle actin and type I collagen was significantly up-regulated, whereas BMP6 exhibited the opposite trend. Additionally, we found icariin could alleviate tubulointerstitial fibrosis by downregulation the miR-320a-3p expression. In conclusion, miR-320a-3p promotes tubulointerstitial fibrosis during the development of DN by suppressing BMP signal pathway activity via inhibiting BMP6 expression. Suggesting that miR-320a-3p represents a potential therapeutic target for tubulointerstitial fibrosis induced by diabetic nephropathy.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"154 4","pages":"Pages 316-325"},"PeriodicalIF":3.5,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000240/pdfft?md5=5fc125f051c623748311765e84eb65b5&pid=1-s2.0-S1347861324000240-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140010803","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

Identification of tumor-suppressive miRNAs that target amino acid transporter LAT1 and exhibit anti-proliferative effects on cholangiocarcinoma cells 鉴定靶向氨基酸转运体 LAT1 并对胆管癌细胞具有抗增殖作用的抑癌 miRNAs

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2024-02-24 DOI: 10.1016/j.jphs.2024.02.012

Xingming Liu , Kou Nishikubo , Ryuichi Ohgaki , Hiroki Okanishi , Suguru Okuda , Minhui Xu , Yoshikatsu Kanai

{"title":"Identification of tumor-suppressive miRNAs that target amino acid transporter LAT1 and exhibit anti-proliferative effects on cholangiocarcinoma cells","authors":"Xingming Liu , Kou Nishikubo , Ryuichi Ohgaki , Hiroki Okanishi , Suguru Okuda , Minhui Xu , Yoshikatsu Kanai","doi":"10.1016/j.jphs.2024.02.012","DOIUrl":"10.1016/j.jphs.2024.02.012","url":null,"abstract":"<div><p>Amino acid transporter LAT1 is highly upregulated in various cancer types, including cholangiocarcinoma (CHOL), and contributes to the rapid proliferation of cancer cells and disease progression. However, the molecular mechanisms underlying the pathological upregulation of LAT1 remain largely unknown. This study pursued the possibility of miRNA-mediated regulation of the LAT1 expression in CHOL cells. Using online target prediction methods, we extracted five candidate miRNAs commonly predicted to regulate the LAT1 expression. Three of them, miR-194-5p, miR-122-5p, and miR-126-3p, were significantly downregulated in CHOL cancer compared to normal tissues. Correlation analysis revealed weak-to-moderate negative correlations between the expression of these miRNAs and LAT1 mRNA in CHOL cancer tissues. We selected miR-194-5p and miR-122-5p for further analyses and found that both miRNAs functionally target 3′UTR of LAT1 mRNA by a luciferase-based reporter assay. Transfection of the miRNA mimics significantly suppressed the LAT1 expression at mRNA and protein levels and inhibited the proliferation of CHOL cells, with a trend of affecting intracellular amino acids and amino acid-related signaling pathways. This study indicates that the decreased expression of these LAT1-targeting tumor-suppressive miRNAs contributes to the upregulation of LAT1 and the proliferation of CHOL cells, highlighting their potential for developing novel cancer therapeutics and diagnostics.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"154 4","pages":"Pages 301-311"},"PeriodicalIF":3.5,"publicationDate":"2024-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000239/pdfft?md5=9adf6144f5deb4537a797a8cd08e9b83&pid=1-s2.0-S1347861324000239-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139954619","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

Effects of D-allose on ATP production and cell viability in neonatal rat cardiomyocytes D-allose 对新生大鼠心肌细胞 ATP 生成和细胞活力的影响

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2024-02-15 DOI: 10.1016/j.jphs.2024.02.009

Xi Chen , Asadur Rahman , Steeve Akumwami , Asahiro Morishita , Kento Kitada , Yasumasa Ikeda , Masafumi Funamoto , Akira Nishiyama

引用次数: 0

Chronic stress alters lipid mediator profiles associated with immune-related gene expressions and cell compositions in mouse bone marrow and spleen 慢性应激改变了小鼠骨髓和脾脏中与免疫相关基因表达和细胞组成有关的脂质介质谱系

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2024-02-15 DOI: 10.1016/j.jphs.2024.02.010

Io Horikawa , Hirotaka Nagai , Masayuki Taniguchi , Guowei Chen , Masakazu Shinohara , Tomohide Suzuki , Shinichi Ishii , Yoshio Katayama , Shiho Kitaoka , Tomoyuki Furuyashiki

{"title":"Chronic stress alters lipid mediator profiles associated with immune-related gene expressions and cell compositions in mouse bone marrow and spleen","authors":"Io Horikawa , Hirotaka Nagai , Masayuki Taniguchi , Guowei Chen , Masakazu Shinohara , Tomohide Suzuki , Shinichi Ishii , Yoshio Katayama , Shiho Kitaoka , Tomoyuki Furuyashiki","doi":"10.1016/j.jphs.2024.02.010","DOIUrl":"10.1016/j.jphs.2024.02.010","url":null,"abstract":"<div><p>Despite the importance of lipid mediators in stress and depression and their link to inflammation, the influence of stress on these mediators and their role in inflammation is not fully understood. This study used RNA-seq, LC-MS/MS, and flow cytometry analyses in a mouse model subjected to chronic social defeat stress to explore the effects of acute and chronic stress on lipid mediators, gene expression, and cell population in the bone marrow and spleen. In the bone marrow, chronic stress induced a sustained transition from lymphoid to myeloid cells, accompanied by corresponding changes in gene expression. This change was associated with decreased levels of 15-deoxy-d12,14-prostaglandin J<sub>2</sub>, a lipid mediator that inhibits inflammation. In the spleen, chronic stress also induced a lymphoid-to-myeloid transition, albeit transiently, alongside gene expression changes indicative of extramedullary hematopoiesis. These changes were linked to lower levels of 12-HEPE and resolvins, both critical for inhibiting and resolving inflammation. Our findings highlight the significant role of anti-inflammatory and pro-resolving lipid mediators in the immune responses induced by chronic stress in the bone marrow and spleen. This study paves the way for understanding how these lipid mediators contribute to the immune mechanisms of stress and depression.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"154 4","pages":"Pages 279-293"},"PeriodicalIF":3.5,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000215/pdfft?md5=d0923d053b1625bac5010259dd286bd9&pid=1-s2.0-S1347861324000215-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139833182","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