Clinical and Experimental Pharmacology and Physiology最新文献

{"title":"GQ-130, a novel analogue of thiazolidinedione, improves obesity-induced metabolic alterations in rats: Evidence for the involvement of PPARβ/δ pathway.","authors":"Odair Alves Silva,&nbsp;Helder Veras Ribeiro-Filho,&nbsp;Thayna Mendonca Avelino,&nbsp;Thais Helena Tittanegro,&nbsp;Ana Carolina Migliorini Figueira,&nbsp;Luiza Antas Rabelo,&nbsp;Ivan da Rocha Pitta,&nbsp;Saad Lahlou,&nbsp;Glória Pinto Duarte","doi":"10.1111/1440-1681.13252","DOIUrl":"https://doi.org/10.1111/1440-1681.13252","url":null,"abstract":"<p><p>The present investigation aimed to characterize the effect of a short-time treatment with a new thiazolidinedione (TZD) derivative, GQ-130, on metabolic alterations in rats fed a high-fat diet (HFD). We investigated whether metabolic alterations induced by GQ-130 were mediated though a mechanism that involves PPARβ/δ transactivation. Potential binding and transactivation of PPARα, PPARβ/δ or PPARγ by GQ-130 were examined through cell transactivation, 8-anilino-1-naphthalenesulfonic acid (ANS) fluorescence quenching assays and thermal shift assay. For in vivo experiments, male 8-week-old Wistar rats were divided into three groups fed for 6 weeks with: (a) a standard rat chow (14% fat) (control group), (b) a HFD (57.8% fat) alone (HFD group), or (c) a HFD associated with an oral treatment with GQ-130 (10 mg/kg/d) during the last week (HFD-GQ group). In 293T cells, unlike rosiglitazone, GQ-130 did not cause significant transactivation of PPARγ but was able to activate PPARβ/δ by 153.9 folds in comparison with control values (DMSO). Surprisingly, ANS fluorescence quenching assay reveals that GQ-130 does not bind directly to PPARβ/δ binding site, a finding that was further corroborated by thermal shift assay which evaluates the thermal stability of PPARβ/δ in the presence of GQ-130. Compared to the control group, rats of the HFD group showed obesity, increased systolic blood pressure (SBP), insulin resistance, impaired glucose intolerance, hyperglycaemia, and dyslipidaemia. GQ-130 treatment abolished the increased SBP and improved all metabolic dysfunctions observed in the HFD group. Oral treatment with GQ-130 was effective in improving HFD-induced metabolic alterations probably through a mechanism that involves PPARβ/δ activation.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"47 5","pages":"798-808"},"PeriodicalIF":0.0,"publicationDate":"2020-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13252","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37518337","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}

{"title":"Enhancing effects of anagliptin on myoblast differentiation and the expression of mitochondrial biogenetic factors in C2C12 mouse skeletal muscle cells.","authors":"Se Eun Han,&nbsp;Su Jin Kim,&nbsp;Young Il Kim,&nbsp;Il Sung Nam-Goong,&nbsp;Hyo Won Jung,&nbsp;Eun Sook Kim","doi":"10.1111/1440-1681.13255","DOIUrl":"https://doi.org/10.1111/1440-1681.13255","url":null,"abstract":"<p><p>To investigate the regulatory effects of anagliptin, a DPP-IV inhibitor used to treat type 2 diabetes mellitus (T2DM), on myoblast differentiation and mitochondrial biogenesis in C2C12 mouse skeletal muscle cells. C2C12 myoblasts were differentiated into myotubes and then treated with anagliptin (10, 25, and 50 μmol/L) for 24 hours. In C2C12 myotubes, anagliptin treatment was significantly increased the expression of MHC, PGC1α, Sirt-1, NRF-1, and TFAM and the phosphorylation of AMPK and ACC in a concentration-dependent manner. Anagliptin also significantly increased the total ATP levels in the myotubes. These results suggest that anagliptin can help prevent skeletal muscle dysfunction in T2DM by promotion of myoblast differentiation and enhancement of energy production via upregulation of mitochondrial biogenetic factors and activation of the AMPK/ACC signalling pathway.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"47 5","pages":"903-906"},"PeriodicalIF":0.0,"publicationDate":"2020-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13255","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37546980","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}

{"title":"Asparaginase induces selective dose- and time-dependent cytotoxicity, apoptosis, and reduction of NFκB expression in oral cancer cells.","authors":"Gabriel Álvares Borges,&nbsp;Silvia Taveira Elias,&nbsp;Tassiana Souza De Araujo,&nbsp;Paula Monteiro Souza,&nbsp;Carlos Henrique Viesi Nascimento-Filho,&nbsp;Rogerio M Castilho,&nbsp;Cristiane H Squarize,&nbsp;Pérola de Oliveira Magalhães,&nbsp;Eliete Neves Silva Guerra","doi":"10.1111/1440-1681.13256","DOIUrl":"https://doi.org/10.1111/1440-1681.13256","url":null,"abstract":"<p><p>Asparaginase is fundamental to the treatment of haematological malignancies. However, little has been studied on the effects that asparaginase could exert on solid tumours. Thus, this study aimed to evaluate the effects of asparaginase on an oral carcinoma cell line. The cytotoxicity of asparaginase in SCC-9 (tongue squamous cell carcinoma) and HaCaT (human keratinocyte) cell lines was evaluated with MTT cell viability assay. The cells were treated with asparaginase at 0.04, 0.16, 0.63, 1.0, 1.5, 2.5, and 5.0 IU/mL. Dose-response curves and IC₅₀ values were obtained and the Tumour Selectivity Index (TSI) was calculated. The effect of asparaginase on procaspase-3 and nuclear factor κB (NFκB) expression was evaluated with western blot because it was reported that the overexpression of NFκB has been shown to contribute to tumour cell survival, proliferation, and migration. Caspase 3/7 staining was performed to identify cell death using flow cytometry. Effective asparaginase concentrations were lower for SCC-9 cells when compared to HaCaT cells. The cytotoxicity results at 48 and 72 hours were significantly different for SCC-9 cells. The TSI indicated that asparaginase was selective for the tumour cells. A decrease in procaspase-3 and NFκB protein levels was observed in SCC-9 cells. Furthermore, asparaginase resulted in significant apoptosis after 48 and 72 hours. Based on these results, asparaginase was cytotoxic in a dose- and time-dependent manner, induces apoptosis, and reduces NFκB expression in oral cancer cells. These results encourage further studies on the effectiveness of this enzyme as a treatment for solid tumours, especially head and neck cancer.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"47 5","pages":"857-866"},"PeriodicalIF":0.0,"publicationDate":"2020-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13256","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37548534","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}

{"title":"Long non-coding RNA LEF1-AS1 is involved in the progression of retinoblastoma through regulating the Wnt/β-catenin pathway.","authors":"Hua He,&nbsp;Mu Qin","doi":"10.1111/1440-1681.13263","DOIUrl":"https://doi.org/10.1111/1440-1681.13263","url":null,"abstract":"<p><p>The lymphoid enhancer binding factor 1 antisense RNA 1 (LEF1-AS1) has been suggested to function as a tumour-associated lncRNA in several types of human cancers, but there is no study to date about the role of LEF1-AS1 in retinoblastoma. In our study, LEF1-AS1 expression was increased in retinoblastoma tissues and cell lines compared with paired adjacent normal tissues and the retinal pigment epithelial cell line, respectively. Meanwhile, we found that patients with retinoblastoma with IIRC D-E or undifferentiated type had notably higher levels of LEF1-AS1 expression than those with IIRC A-C or differentiated type. High LEF1-AS1 expression predicted poor disease-free survival in patients with retinoblastoma. The in vitro assays suggested that silencing of LEF1-AS1 suppressed retinoblastoma cell proliferation, migration, and invasion through regulating the Wnt/β-catenin pathway. In conclusion, LEF1-AS1 functions as an oncogenic lncRNA in retinoblastoma.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"47 5","pages":"886-891"},"PeriodicalIF":0.0,"publicationDate":"2020-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13263","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37586828","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}

{"title":"MicroRNA-876-5p represses the cell proliferation and invasion of colorectal cancer through suppressing YAP signalling via targeting RASAL2.","authors":"Li Ren,&nbsp;Zhiyong Zhang,&nbsp;Yun Feng,&nbsp;Miaosha Luo,&nbsp;Zhiming Hao","doi":"10.1111/1440-1681.13264","DOIUrl":"https://doi.org/10.1111/1440-1681.13264","url":null,"abstract":"<p><p>Aberrant expression of microRNA-876-5p (miR-876-5p) is implicated in the progression of multiple human cancers. However, the potential role of miR-876-5p in colorectal cancer remains poorly understood. The purpose of the current study was to investigate the potential role of miR-876-5p in colorectal cancer. miR-876-5p expression was significantly downregulated in colorectal cancer tissues and cell lines compared with normal controls. Gain-of-function assays revealed that miR-876-5p overexpression effectively repressed the malignant behaviours of colorectal cancer cells, including cell proliferation, colony formation, and invasion. Bioinformatics analysis predicted that RAS protein activator like 2 (RASAL2), a potential oncogene for colorectal cancer, is a putative miR-876-5p target gene. A luciferase reporter assay confirmed that miR-876-5p directly binds to the 3'-untranslated region (UTR) of RASAL2. Furthermore, both RASAL2 messenger RNA (mRNA) and protein expression were negatively modulated by miR-876-5p in colorectal cancer cells. Notably, there was an inverse correlation between miR-876-5p and RASAL2 expression in colorectal cancer tissue specimens. Moreover, miR-876-5p was involved in regulating the activation of Yes-associated protein (YAP) signalling through inhibiting RASAL2. However, the miR-876-5p-mediated antitumour effect on colorectal cancer cells was partially reversed by restoring RASAL2 expression. Notably, miR-876-5p upregulation impeded the tumour growth of colorectal cancer cells in vivo in nude mice. Overall, these results demonstrated that miR-876-5p exerts an antitumour function in colorectal cancer by targeting RASAL2 to suppress YAP signalling activation. These findings highlight the importance of the miR-876-5p/RASAL2/YAP axis in colorectal cancer progression and suggest that miR-876-5p is a potential therapeutic target for treating colorectal cancer.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"47 5","pages":"867-876"},"PeriodicalIF":0.0,"publicationDate":"2020-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13264","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37586826","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}

{"title":"Long non-coding RNA UCA1 promotes autophagy by targeting miR-96-5p in acute myeloid leukaemia.","authors":"Jia Jia Li,&nbsp;Xiao Feng Chen,&nbsp;Meng Wang,&nbsp;Ping Ping Zhang,&nbsp;Feng Zhang,&nbsp;Jing Jing Zhang","doi":"10.1111/1440-1681.13259","DOIUrl":"https://doi.org/10.1111/1440-1681.13259","url":null,"abstract":"<p><p>Long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) has been identified as an oncogene and is involved in acute myeloid leukaemia (AML). Autophagy contributes to tumourigenesis and cancer cell survival. The purpose of this study was to investigate the regulatory role and mechanism of UCA1 in AML cell viability by its effect on autophagy. The expression of UCA1, miR-96-5p, and ATG7 was determined by qRT-PCR and western blot. Cell proliferation was examined by MTT assay. The autophagy level was assessed by green fluorescent protein (GFP)-LC3 immunofluorescence and western blot. The interaction between UCA1 and miR-96-5p or ATG7 was analyzed by luciferase reporter activity. The results showed that UCA1 promoted AML cell proliferation by inducing autophagy. Mechanistically, UCA1 acted as a sponge of miR-96-5p by binding to miR-96-5p. ATG7 was a direct target of miR-96-5p and positively regulated by UCA1. Further results showed that the miR-96-5p mimic effectively counteracted the UCA1 overexpression-mediated induction of the ATG7/autophagy pathway. Collectively, UCA1 functions as a sponge of miR-96-5p to upregulate its target ATG7, thereby resulting in autophagy induction. Our findings reveal a UCA1-mediated molecular mechanism responsible for autophagy induction in AML and help to improve the understanding of the molecular mechanism of AML progression.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"47 5","pages":"877-885"},"PeriodicalIF":0.0,"publicationDate":"2020-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13259","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37555538","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}

{"title":"The concurrent exposure to aluminium and fructose induces liver injury in rats: Protection by monoammonium glycyrrhizinate.","authors":"Sarah Zakaria,&nbsp;Rehab A Hasan,&nbsp;Mona F Mahmoud,&nbsp;Hassan M El Fayoumi,&nbsp;Amr A A Mahmoud","doi":"10.1111/1440-1681.13257","DOIUrl":"https://doi.org/10.1111/1440-1681.13257","url":null,"abstract":"<p><p>Aluminium is a ubiquitous element that occurs naturally in the soil making human exposure to it unavoidable. It is implicated in the aetiology of different neurodegenerative diseases and can induce liver injury. In addition, insulin resistance (IR) plays an essential role in the pathogenesis and the progression of liver disorders. The increased consumption of fructose contained in soft drinks and western pattern diet results in IR that along with the wide distribution of aluminium make the concurrent exposure conceivable and increase the risk of liver injury. Therefore, the present study explores the hepatotoxic effects of aluminium and fructose administered concurrently and evaluates the possible protection by monoammonium glycyrrhizinate (MAG). Liver injury was induced by the administration of aluminium chloride (34 mg/kg/d) plus 10% (w/v) fructose in drinking water. Male rats were treated with either MAG (40 mg/kg/d) or silymarin (SIL, 100 mg/kg/d). The concurrent administration of aluminium and fructose (FRUAL) induced liver injury manifested as a significant elevation of serum liver enzymes activities, bilirubin level, and prothrombin time, as well as reduction of albumin level. On the other hand, the administration of MAG improved the FRUAL-induced aberrations of liver function tests and hepatic cytoarchitecture. We assume that the MAG-induced suppression of oxidative stress, toll-like receptor 4 pathway activation, inflammation, and apoptosis might play a crucial role in the hepatoprotective effect of MAG in this model. Intriguingly, the hepatoprotective effect MAG against FRUAL-induced liver injury surpasses that of the gold standard SIL, suggesting MAG as a better alternative to SIL.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"47 5","pages":"809-820"},"PeriodicalIF":0.0,"publicationDate":"2020-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13257","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37548629","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}

{"title":"Alpha-pinene promotes osteoblast differentiation and attenuates TNFα-induced inhibition of differentiation in MC3T3-E1 pre-osteoblasts.","authors":"Hyeon-Young Min,&nbsp;Hyo-Eun Son,&nbsp;Won-Gu Jang","doi":"10.1111/1440-1681.13245","DOIUrl":"https://doi.org/10.1111/1440-1681.13245","url":null,"abstract":"<p><p>Alpha-pinene (α-pinene) is an organic compound, found in the oils of many species of coniferous trees, especially pine. α-Pinene reportedly has antioxidant and anti-inflammatory activities; however, its effects on osteoblasts are unknown. This study investigated the effects of α-pinene on osteoblast differentiation and tumour necrosis factor-alpha (TNFα)-induced inhibition of osteogenesis. Culture in control or osteogenic medium containing α-pinene increased osteogenic marker expression. Alkaline phosphatase staining and alizarin red S staining confirmed that α-pinene enhanced osteoblast differentiation. Also, α-pinene attenuated TNFα-induced inhibition of Smad1/5/9 phosphorylation and extracellular matrix mineralization. Taken together, our findings suggest that α-pinene enhances osteoblast differentiation and mineralization in MC3T3-E1 pre-osteoblasts.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"47 5","pages":"831-837"},"PeriodicalIF":0.0,"publicationDate":"2020-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13245","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37496479","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}

{"title":"Role of omega-6 and omega-3 fatty acids in fetal programming.","authors":"Nirajan Shrestha,&nbsp;Simone L Sleep,&nbsp;James S M Cuffe,&nbsp;Olivia J Holland,&nbsp;Anthony V Perkins,&nbsp;Suk Yu Yau,&nbsp;Andrew J McAinch,&nbsp;Deanne H Hryciw","doi":"10.1111/1440-1681.13244","DOIUrl":"https://doi.org/10.1111/1440-1681.13244","url":null,"abstract":"<p><p>Maternal nutrition plays a critical role in fetal development and can influence adult onset of disease. Linoleic acid (LA) and alpha-linolenic acid (ALA) are major omega-6 (n-6) and n-3 polyunsaturated fatty acids (PUFA), respectively, that are essential in our diet. LA and ALA are critical for the development of the fetal neurological and immune systems. However, in recent years, the consumption of n-6 PUFA has increased gradually worldwide, and elevated n-6 PUFA consumption may be harmful to human health. Consumption of diets with high levels of n-6 PUFA before or during pregnancy may have detrimental effects on fetal development and may influence overall health of offspring in adulthood. This review discusses the role of n-6 PUFA in fetal programming, the importance of a balance between n-6 and n-3 PUFAs in the maternal diet, and the need of further animal models and human studies that critically evaluate both n-6 and n-3 PUFA contents in diets.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"47 5","pages":"907-915"},"PeriodicalIF":0.0,"publicationDate":"2020-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13244","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37496481","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}

{"title":"Lithium attenuates d-amphetamine-induced hyperlocomotor activity in mice via inhibition of interaction between cyclooxygenase-2 and indoleamine-2,3-dioxygenase.","authors":"Dieu-Hien Phan,&nbsp;Eun-Joo Shin,&nbsp;Ji Hoon Jeong,&nbsp;Hai-Quyen Tran,&nbsp;Naveen Sharma,&nbsp;Bao Trong Nguyen,&nbsp;Tae Woo Jung,&nbsp;Seung-Yeol Nah,&nbsp;Kuniaki Saito,&nbsp;Toshitaka Nabeshima,&nbsp;Hyoung-Chun Kim","doi":"10.1111/1440-1681.13243","DOIUrl":"https://doi.org/10.1111/1440-1681.13243","url":null,"abstract":"<p><p>In the present study, we investigated whether mood stabilizer lithium (Li) protects against d-amphetamine (AMP)-induced mania-like behaviours via modulating the novel proinflammatory potential. Repeated treatment with AMP resulted in significant increases in proinflammatory cyclooxygenase-2 (COX-2) and indolemaine-2,3-dioxygenase-1 (IDO)-1 expression in the prefrontal cortex (PFC) of mice. However, AMP treatment did not significantly change IDO-2 and 5-lipoxygenase (5-LOX) expression, suggesting that proinflammatory parameters such as COX-2 and IDO-1 are specific for AMP-induced behaviours. AMP-induced initial expression of COX-2 (15 minutes post-AMP) was earlier than that of IDO-1 (1 hour post-AMP). Mood stabilizer Li and COX-2 inhibitor meloxicam significantly attenuated COX-2 expression 15 minutes post-AMP, whereas IDO-1 inhibitor 1-methyl-DL-tryptophan (1-MT) did not affect COX-2 expression. However, AMP-induced IDO-1 expression was significantly attenuated by Li, meloxicam or 1-MT, suggesting that COX-2 is an upstream molecule for the induction of IDO-1 caused by AMP. Consistently, co-immunoprecipitation between COX-2 and IDO-1 was observed at 30 minutes, 1, 3, and 6 hours after the final AMP treatment. This interaction was also significantly inhibited by Li, meloxicam or 1-MT. Furthermore, AMP-induced hyperlocomotion was significantly attenuated by Li, meloxicam or 1-MT. We report, for the first time, that mood stabilizer Li attenuates AMP-induced mania-like behaviour via attenuation of interaction between COX-2 and IDO-1, and that the interaction of COX-2 and IDO-1 may be critical for the therapeutic intervention mediated by mood stabilizer.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"47 5","pages":"790-797"},"PeriodicalIF":0.0,"publicationDate":"2020-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13243","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37496501","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}