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General regulatory factors exert differential effects on nucleosome sliding activity of the ISW1a complex 一般调控因子对 ISW1a 复合物的核小体滑动活性产生不同影响
IF 6.7 2区 生物学
Biological Research Pub Date : 2024-05-04 DOI: 10.1186/s40659-024-00500-6
Andrea Oyarzún-Cisterna, Cristián Gidi, Fernanda Raiqueo, Roberto Amigo, Camila Rivas, Marcela Torrejón, José L. Gutiérrez
{"title":"General regulatory factors exert differential effects on nucleosome sliding activity of the ISW1a complex","authors":"Andrea Oyarzún-Cisterna, Cristián Gidi, Fernanda Raiqueo, Roberto Amigo, Camila Rivas, Marcela Torrejón, José L. Gutiérrez","doi":"10.1186/s40659-024-00500-6","DOIUrl":"https://doi.org/10.1186/s40659-024-00500-6","url":null,"abstract":"Chromatin dynamics is deeply involved in processes that require access to DNA, such as transcriptional regulation. Among the factors involved in chromatin dynamics at gene regulatory regions are general regulatory factors (GRFs). These factors contribute to establishment and maintenance of nucleosome-depleted regions (NDRs). These regions are populated by nucleosomes through histone deposition and nucleosome sliding, the latter catalyzed by a number of ATP-dependent chromatin remodeling complexes, including ISW1a. It has been observed that GRFs can act as barriers against nucleosome sliding towards NDRs. However, the relative ability of the different GRFs to hinder sliding activity is currently unknown. Considering this, we performed a comparative analysis for the main GRFs, with focus in their ability to modulate nucleosome sliding mediated by ISW1a. Among the GRFs tested in nucleosome remodeling assays, Rap1 was the only factor displaying the ability to hinder the activity of ISW1a. This effect requires location of the Rap1 cognate sequence on linker that becomes entry DNA in the nucleosome remodeling process. In addition, Rap1 was able to hinder nucleosome assembly in octamer transfer assays. Concurrently, Rap1 displayed the highest affinity for and longest dwell time from its target sequence, compared to the other GRFs tested. Consistently, through bioinformatics analyses of publicly available genome-wide data, we found that nucleosome occupancy and histone deposition in vivo are inversely correlated with the affinity of Rap1 for its target sequences in the genome. Our findings point to DNA binding affinity, residence time and location at particular translational positions relative to the nucleosome core as the key features of GRFs underlying their roles played in nucleosome sliding and assembly.","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140841093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The effect of diabetes mellitus on differentiation of mesenchymal stem cells into insulin-producing cells 糖尿病对间充质干细胞分化为胰岛素分泌细胞的影响
IF 6.7 2区 生物学
Biological Research Pub Date : 2024-05-02 DOI: 10.1186/s40659-024-00502-4
Omar I. Badr, Mohamed M. Kamal, Shohda A. El-Maraghy, Heba R. Ghaiad
{"title":"The effect of diabetes mellitus on differentiation of mesenchymal stem cells into insulin-producing cells","authors":"Omar I. Badr, Mohamed M. Kamal, Shohda A. El-Maraghy, Heba R. Ghaiad","doi":"10.1186/s40659-024-00502-4","DOIUrl":"https://doi.org/10.1186/s40659-024-00502-4","url":null,"abstract":"Diabetes mellitus (DM) is a global epidemic with increasing incidences. DM is a metabolic disease associated with chronic hyperglycemia. Aside from conventional treatments, there is no clinically approved cure for DM up till now. Differentiating mesenchymal stem cells (MSCs) into insulin-producing cells (IPCs) is a promising approach for curing DM. Our study was conducted to investigate the effect of DM on MSCs differentiation into IPCs in vivo and in vitro. We isolated adipose-derived mesenchymal stem cells (Ad-MSCs) from the epididymal fat of normal and STZ-induced diabetic Sprague–Dawley male rats. Afterwards, the in vitro differentiation of normal-Ad-MSCs (N-Ad-MSCs) and diabetic-Ad-MSCs (DM-Ad-MSCs) into IPCs was compared morphologically then through determining the gene expression of β-cell markers including neurogenin-3 (Ngn-3), homeobox protein (Nkx6.1), musculoaponeurotic fibrosarcoma oncogene homolog A (MafA), and insulin-1 (Ins-1) and eventually, through performing glucose-stimulated insulin secretion test (GSIS). Finally, the therapeutic potential of N-Ad-MSCs and DM-Ad-MSCs transplantation was compared in vivo in STZ-induced diabetic animals. Our results showed no significant difference in the characteristics of N-Ad-MSCs and DM-Ad-MSCs. However, we demonstrated a significant difference in their abilities to differentiate into IPCs in vitro morphologically in addition to β-cell markers expression, and functional assessment via GSIS test. Furthermore, the abilities of both Ad-MSCs to control hyperglycemia in diabetic rats in vivo was assessed through measuring fasting blood glucose (FBGs), body weight (BW), histopathological examination of both pancreas and liver and immunoexpression of insulin in pancreata of study groups. Our findings reveal the effectiveness of N-Ad-MSCs in differentiating into IPCs in vitro and controlling the hyperglycemia of STZ-induced diabetic rats in vivo compared to DM-Ad-MSCs. ","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140841327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Control of astrocytic Ca2+ signaling by nitric oxide-dependent S-nitrosylation of Ca2+ homeostasis modulator 1 channels 一氧化氮依赖的钙离子平衡调节器 1 通道 S-亚硝基化对星形胶质细胞钙离子信号的控制
IF 6.7 2区 生物学
Biological Research Pub Date : 2024-04-30 DOI: 10.1186/s40659-024-00503-3
Mariela Puebla, Manuel F. Muñoz, Mauricio A. Lillo, Jorge E. Contreras, Xavier F. Figueroa
{"title":"Control of astrocytic Ca2+ signaling by nitric oxide-dependent S-nitrosylation of Ca2+ homeostasis modulator 1 channels","authors":"Mariela Puebla, Manuel F. Muñoz, Mauricio A. Lillo, Jorge E. Contreras, Xavier F. Figueroa","doi":"10.1186/s40659-024-00503-3","DOIUrl":"https://doi.org/10.1186/s40659-024-00503-3","url":null,"abstract":"Astrocytes Ca2+ signaling play a central role in the modulation of neuronal function. Activation of metabotropic glutamate receptors (mGluR) by glutamate released during an increase in synaptic activity triggers coordinated Ca2+ signals in astrocytes. Importantly, astrocytes express the Ca2+-dependent nitric oxide (NO)-synthetizing enzymes eNOS and nNOS, which might contribute to the Ca2+ signals by triggering Ca2+ influx or ATP release through the activation of connexin 43 (Cx43) hemichannels, pannexin-1 (Panx-1) channels or Ca2+ homeostasis modulator 1 (CALHM1) channels. Hence, we aim to evaluate the participation of NO in the astrocytic Ca2+ signaling initiated by stimulation of mGluR in primary cultures of astrocytes from rat brain cortex. Astrocytes were stimulated with glutamate or t-ACPD and NO-dependent changes in [Ca2+]i and ATP release were evaluated. In addition, the activity of Cx43 hemichannels, Panx-1 channels and CALHM1 channels was also analyzed. The expression of Cx43, Panx-1 and CALHM1 in astrocytes was confirmed by immunofluorescence analysis and both glutamate and t-ACPD induced NO-mediated activation of CALHM1 channels via direct S-nitrosylation, which was further confirmed by assessing CALHM1-mediated current using the two-electrode voltage clamp technique in Xenopus oocytes. Pharmacological blockade or siRNA-mediated inhibition of CALHM1 expression revealed that the opening of these channels provides a pathway for ATP release and the subsequent purinergic receptor-dependent activation of Cx43 hemichannels and Panx-1 channels, which further contributes to the astrocytic Ca2+ signaling. Our findings demonstrate that activation of CALHM1 channels through NO-mediated S-nitrosylation in astrocytes in vitro is critical for the generation of glutamate-initiated astrocytic Ca2+ signaling.","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140841308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Increased levels and activation of the IL-17 receptor in microglia contribute to enhanced neuroinflammation in cerebellum of hyperammonemic rats 小胶质细胞中 IL-17 受体水平的升高和激活是高氨血症大鼠小脑神经炎症加剧的原因之一
IF 6.7 2区 生物学
Biological Research Pub Date : 2024-04-27 DOI: 10.1186/s40659-024-00504-2
Yaiza M Arenas, Adrià López-Gramaje, C. Montoliu, M. Llansola, Vicente Felipo
{"title":"Increased levels and activation of the IL-17 receptor in microglia contribute to enhanced neuroinflammation in cerebellum of hyperammonemic rats","authors":"Yaiza M Arenas, Adrià López-Gramaje, C. Montoliu, M. Llansola, Vicente Felipo","doi":"10.1186/s40659-024-00504-2","DOIUrl":"https://doi.org/10.1186/s40659-024-00504-2","url":null,"abstract":"","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140652175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Identification and expression analysis of two steamer-like retrotransposons in the Chilean blue mussel (Mytilus chilensis) 智利蓝贻贝(Mytilus chilensis)中两个类似蒸汽机的转座子的鉴定和表达分析
IF 6.7 2区 生物学
Biological Research Pub Date : 2024-04-26 DOI: 10.1186/s40659-024-00498-x
Gloria Arriagada, Johan Quezada, Nicolas Merino-Veliz, Fernando Avilés, Diana Tapia-Cammas, Jorge Gomez, Daniela Curotto, Juan A. Valdes, Pablo A. Oyarzún, Cristian Gallardo-Escárate, Michael J. Metzger, Marco Alvarez
{"title":"Identification and expression analysis of two steamer-like retrotransposons in the Chilean blue mussel (Mytilus chilensis)","authors":"Gloria Arriagada, Johan Quezada, Nicolas Merino-Veliz, Fernando Avilés, Diana Tapia-Cammas, Jorge Gomez, Daniela Curotto, Juan A. Valdes, Pablo A. Oyarzún, Cristian Gallardo-Escárate, Michael J. Metzger, Marco Alvarez","doi":"10.1186/s40659-024-00498-x","DOIUrl":"https://doi.org/10.1186/s40659-024-00498-x","url":null,"abstract":"Disseminated neoplasia (DN) is a proliferative cell disorder of the circulatory system of bivalve mollusks. The disease is transmitted between individuals and can also be induced by external chemical agents such as bromodeoxyuridine. In Mya arenaria, we have cloned and characterized an LTR-retrotransposon named Steamer. Steamer mRNA levels and gene copy number correlates with DN and can be used as a marker of the disease. So far, the only mollusk where a retrotransposon expression relates to DN is Mya arenaria. On the other hand, it has been reported that the Chilean blue mussel Mytilus chilensis can also suffers DN. Our aim was to identify retrotransposons in Mytilus chilensis and to study their expression levels in the context of disseminated neoplasia. Here we show that 7.1% of individuals collected in August 2018, from two farming areas, presents morphological characteristics described in DN. Using Steamer sequence to interrogate the transcriptome of M. chilensis we found two putative retrotransposons, named Steamer-like elements (MchSLEs). MchSLEs are present in the genome of M. chilensis and MchSLE1 is indeed an LTR-retrotransposon. Neither expression, nor copy number of the reported MchSLEs correlate with DN status but both are expressed at different levels among individual animals. We also report that in cultured M. chilensis haemocytes MchSLEs1 expression can be induced by bromodeoxyuridine. We conclude that SLEs present in Mytilus chilensis are differentially expressed among individuals and do not correlate with disseminated neoplasia. Treatment of haemocytes with a stressor like bromodeoxyuridine induces expression of MchSLE1 suggesting that in Mytilus chilensis environmental stressors can induce activation of LTR-retrotransposon.","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140801070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Noncoding RNAs in skeletal development and disorders 骨骼发育和骨骼疾病中的非编码 RNA
IF 6.7 2区 生物学
Biological Research Pub Date : 2024-04-22 DOI: 10.1186/s40659-024-00497-y
Qing Yao, Tailin He, Jian-You Liao, Rongdong Liao, Xiaohao Wu, Lijun Lin, Guozhi Xiao
{"title":"Noncoding RNAs in skeletal development and disorders","authors":"Qing Yao, Tailin He, Jian-You Liao, Rongdong Liao, Xiaohao Wu, Lijun Lin, Guozhi Xiao","doi":"10.1186/s40659-024-00497-y","DOIUrl":"https://doi.org/10.1186/s40659-024-00497-y","url":null,"abstract":"Protein-encoding genes only constitute less than 2% of total human genomic sequences, and 98% of genetic information was previously referred to as “junk DNA”. Meanwhile, non-coding RNAs (ncRNAs) consist of approximately 60% of the transcriptional output of human cells. Thousands of ncRNAs have been identified in recent decades, and their essential roles in the regulation of gene expression in diverse cellular pathways associated with fundamental cell processes, including proliferation, differentiation, apoptosis, and metabolism, have been extensively investigated. Furthermore, the gene regulation networks they form modulate gene expression in normal development and under pathological conditions. In this review, we integrate current information about the classification, biogenesis, and function of ncRNAs and how these ncRNAs support skeletal development through their regulation of critical genes and signaling pathways in vivo. We also summarize the updated knowledge of ncRNAs involved in common skeletal diseases and disorders, including but not limited to osteoporosis, osteoarthritis, rheumatoid arthritis, scoliosis, and intervertebral disc degeneration, by highlighting their roles established from in vivo, in vitro, and ex vivo studies.","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140634361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cx43 hemichannels and panx1 channels contribute to ethanol-induced astrocyte dysfunction and damage Cx43 半通道和 panx1 通道有助于乙醇诱导的星形胶质细胞功能障碍和损伤
IF 6.7 2区 生物学
Biological Research Pub Date : 2024-04-04 DOI: 10.1186/s40659-024-00493-2
Gonzalo I. Gómez, Tanhia F. Alvear, Daniela A. Roa, Arantza Farias-Pasten, Sergio A. Vergara, Luis A. Mellado, Claudio J. Martinez-Araya, Juan Prieto-Villalobos, Claudia García-Rodríguez, Natalia Sánchez, Juan C. Sáez, Fernando C. Ortíz, Juan A. Orellana
{"title":"Cx43 hemichannels and panx1 channels contribute to ethanol-induced astrocyte dysfunction and damage","authors":"Gonzalo I. Gómez, Tanhia F. Alvear, Daniela A. Roa, Arantza Farias-Pasten, Sergio A. Vergara, Luis A. Mellado, Claudio J. Martinez-Araya, Juan Prieto-Villalobos, Claudia García-Rodríguez, Natalia Sánchez, Juan C. Sáez, Fernando C. Ortíz, Juan A. Orellana","doi":"10.1186/s40659-024-00493-2","DOIUrl":"https://doi.org/10.1186/s40659-024-00493-2","url":null,"abstract":"Alcohol, a widely abused drug, significantly diminishes life quality, causing chronic diseases and psychiatric issues, with severe health, societal, and economic repercussions. Previously, we demonstrated that non-voluntary alcohol consumption increases the opening of Cx43 hemichannels and Panx1 channels in astrocytes from adolescent rats. However, whether ethanol directly affects astroglial hemichannels and, if so, how this impacts the function and survival of astrocytes remains to be elucidated. Clinically relevant concentrations of ethanol boost the opening of Cx43 hemichannels and Panx1 channels in mouse cortical astrocytes, resulting in the release of ATP and glutamate. The activation of these large-pore channels is dependent on Toll-like receptor 4, P2X7 receptors, IL-1β and TNF-α signaling, p38 mitogen-activated protein kinase, and inducible nitric oxide (NO) synthase. Notably, the ethanol-induced opening of Cx43 hemichannels and Panx1 channels leads to alterations in cytokine secretion, NO production, gliotransmitter release, and astrocyte reactivity, ultimately impacting survival. Our study reveals a new mechanism by which ethanol impairs astrocyte function, involving the sequential stimulation of inflammatory pathways that further increase the opening of Cx43 hemichannels and Panx1 channels. We hypothesize that targeting astroglial hemichannels could be a promising pharmacological approach to preserve astrocyte function and synaptic plasticity during the progression of various alcohol use disorders.","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140591274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Galectins in epithelial-mesenchymal transition: roles and mechanisms contributing to tissue repair, fibrosis and cancer metastasis 上皮-间质转化过程中的加连蛋白:促进组织修复、纤维化和癌症转移的作用和机制
IF 6.7 2区 生物学
Biological Research Pub Date : 2024-04-04 DOI: 10.1186/s40659-024-00490-5
Elisa Perez-Moreno, Claudia Oyanadel, Adely de la Peña, Ronny Hernández, Francisca Pérez-Molina, Claudia Metz, Alfonso González, Andrea Soza
{"title":"Galectins in epithelial-mesenchymal transition: roles and mechanisms contributing to tissue repair, fibrosis and cancer metastasis","authors":"Elisa Perez-Moreno, Claudia Oyanadel, Adely de la Peña, Ronny Hernández, Francisca Pérez-Molina, Claudia Metz, Alfonso González, Andrea Soza","doi":"10.1186/s40659-024-00490-5","DOIUrl":"https://doi.org/10.1186/s40659-024-00490-5","url":null,"abstract":"Galectins are soluble glycan-binding proteins that interact with a wide range of glycoproteins and glycolipids and modulate a broad spectrum of physiological and pathological processes. The expression and subcellular localization of different galectins vary among tissues and cell types and change during processes of tissue repair, fibrosis and cancer where epithelial cells loss differentiation while acquiring migratory mesenchymal phenotypes. The epithelial-mesenchymal transition (EMT) that occurs in the context of these processes can include modifications of glycosylation patterns of glycolipids and glycoproteins affecting their interactions with galectins. Moreover, overexpression of certain galectins has been involved in the development and different outcomes of EMT. This review focuses on the roles and mechanisms of Galectin-1 (Gal-1), Gal-3, Gal-4, Gal-7 and Gal-8, which have been involved in physiologic and pathogenic EMT contexts.","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140591389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Glutaminolysis regulates endometrial fibrosis in intrauterine adhesion via modulating mitochondrial function. 谷氨酰胺溶解通过调节线粒体功能调节宫腔内粘连的子宫内膜纤维化。
IF 6.7 2区 生物学
Biological Research Pub Date : 2024-04-01 DOI: 10.1186/s40659-024-00492-3
Pei Chen, Chaoshuang Ye, Yunke Huang, Bingning Xu, Tianyu Wu, Yuanhang Dong, Yang Jin, Li Zhao, Changchang Hu, Jingxia Mao, Ruijin Wu
{"title":"Glutaminolysis regulates endometrial fibrosis in intrauterine adhesion via modulating mitochondrial function.","authors":"Pei Chen, Chaoshuang Ye, Yunke Huang, Bingning Xu, Tianyu Wu, Yuanhang Dong, Yang Jin, Li Zhao, Changchang Hu, Jingxia Mao, Ruijin Wu","doi":"10.1186/s40659-024-00492-3","DOIUrl":"10.1186/s40659-024-00492-3","url":null,"abstract":"<p><strong>Background: </strong>Endometrial fibrosis, a significant characteristic of intrauterine adhesion (IUA), is caused by the excessive differentiation and activation of endometrial stromal cells (ESCs). Glutaminolysis is the metabolic process of glutamine (Gln), which has been implicated in multiple types of organ fibrosis. So far, little is known about whether glutaminolysis plays a role in endometrial fibrosis.</p><p><strong>Methods: </strong>The activation model of ESCs was constructed by TGF-β1, followed by RNA-sequencing analysis. Changes in glutaminase1 (GLS1) expression at RNA and protein levels in activated ESCs were verified experimentally. Human IUA samples were collected to verify GLS1 expression in endometrial fibrosis. GLS1 inhibitor and glutamine deprivation were applied to ESCs models to investigate the biological functions and mechanisms of glutaminolysis in ESCs activation. The IUA mice model was established to explore the effect of glutaminolysis inhibition on endometrial fibrosis.</p><p><strong>Results: </strong>We found that GLS1 expression was significantly increased in activated ESCs models and fibrotic endometrium. Glutaminolysis inhibition by GLS1 inhibitor bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl) ethyl sulfide (BPTES or glutamine deprivation treatment suppressed the expression of two fibrotic markers, α-SMA and collagen I, as well as the mitochondrial function and mTORC1 signaling in ESCs. Furthermore, inhibition of the mTORC1 signaling pathway by rapamycin suppressed ESCs activation. In IUA mice models, BPTES treatment significantly ameliorated endometrial fibrosis and improved pregnancy outcomes.</p><p><strong>Conclusion: </strong>Glutaminolysis and glutaminolysis-associated mTOR signaling play a role in the activation of ESCs and the pathogenesis of endometrial fibrosis through regulating mitochondrial function. Glutaminolysis inhibition suppresses the activation of ESCs, which might be a novel therapeutic strategy for IUA.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10983700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140334634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","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 long-chain flavodoxin FldX1 improves the biodegradation of 4-hydroxyphenylacetate and 3-hydroxyphenylacetate and counteracts the oxidative stress associated to aromatic catabolism in Paraburkholderia xenovorans. 长链黄酮毒素 FldX1 可改善 4-hydroxyphenylacetate 和 3-hydroxyphenylacetate 的生物降解,并抵消 Paraburkholderia xenovorans 中与芳香族分解代谢相关的氧化应激。
IF 6.7 2区 生物学
Biological Research Pub Date : 2024-04-01 DOI: 10.1186/s40659-024-00491-4
Laura Rodríguez-Castro, Roberto E Durán, Valentina Méndez, Flavia Dorochesi, Daniela Zühlke, Katharina Riedel, Michael Seeger
{"title":"The long-chain flavodoxin FldX1 improves the biodegradation of 4-hydroxyphenylacetate and 3-hydroxyphenylacetate and counteracts the oxidative stress associated to aromatic catabolism in Paraburkholderia xenovorans.","authors":"Laura Rodríguez-Castro, Roberto E Durán, Valentina Méndez, Flavia Dorochesi, Daniela Zühlke, Katharina Riedel, Michael Seeger","doi":"10.1186/s40659-024-00491-4","DOIUrl":"10.1186/s40659-024-00491-4","url":null,"abstract":"<p><strong>Background: </strong>Bacterial aromatic degradation may cause oxidative stress. The long-chain flavodoxin FldX1 of Paraburkholderia xenovorans LB400 counteracts reactive oxygen species (ROS). The aim of this study was to evaluate the protective role of FldX1 in P. xenovorans LB400 during the degradation of 4-hydroxyphenylacetate (4-HPA) and 3-hydroxyphenylacetate (3-HPA).</p><p><strong>Methods: </strong>The functionality of FldX1 was evaluated in P. xenovorans p2-fldX1 that overexpresses FldX1. The effects of FldX1 on P. xenovorans were studied measuring growth on hydroxyphenylacetates, degradation of 4-HPA and 3-HPA, and ROS formation. The effects of hydroxyphenylacetates (HPAs) on the proteome (LC-MS/MS) and gene expression (qRT-PCR) were quantified. Bioaugmentation with strain p2-fldX1 of 4-HPA-polluted soil was assessed, measuring aromatic degradation (HPLC), 4-HPA-degrading bacteria, and plasmid stability.</p><p><strong>Results: </strong>The exposure of P. xenovorans to 4-HPA increased the formation of ROS compared to 3-HPA or glucose. P. xenovorans p2-fldX1 showed an increased growth on 4-HPA and 3-HPA compared to the control strain WT-p2. Strain p2-fldX1 degraded faster 4-HPA and 3-HPA than strain WT-p2. Both WT-p2 and p2-fldX1 cells grown on 4-HPA displayed more changes in the proteome than cells grown on 3-HPA in comparison to glucose-grown cells. Several enzymes involved in ROS detoxification, including AhpC2, AhpF, AhpD3, KatA, Bcp, CpoF1, Prx1 and Prx2, were upregulated by hydroxyphenylacetates. Downregulation of organic hydroperoxide resistance (Ohr) and DpsA proteins was observed. A downregulation of the genes encoding scavenging enzymes (katE and sodB), and gstA and trxB was observed in p2-fldX1 cells, suggesting that FldX1 prevents the antioxidant response. More than 20 membrane proteins, including porins and transporters, showed changes in expression during the growth of both strains on hydroxyphenylacetates. An increased 4-HPA degradation by recombinant strain p2-fldX1 in soil microcosms was observed. In soil, the strain overexpressing the flavodoxin FldX1 showed a lower plasmid loss, compared to WT-p2 strain, suggesting that FldX1 contributes to bacterial fitness. Overall, these results suggest that recombinant strain p2-fldX1 is an attractive bacterium for its application in bioremediation processes of aromatic compounds.</p><p><strong>Conclusions: </strong>The long-chain flavodoxin FldX1 improved the capability of P. xenovorans to degrade 4-HPA in liquid culture and soil microcosms by protecting cells against the degradation-associated oxidative stress.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10983741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140334574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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