Journal of cellular signaling最新文献

{"title":"Resveratrol and Astaxanthin Protect Primary Human Nasal Epithelial Cells Cultured at an Air-liquid Interface from an Acute Oxidant Exposure.","authors":"Ayaho Yamamoto,&nbsp;Peter D Sly,&nbsp;Nelufa Begum,&nbsp;Abrey J Yeo,&nbsp;Emmanuelle Fantino","doi":"10.33696/signaling.3.084","DOIUrl":"https://doi.org/10.33696/signaling.3.084","url":null,"abstract":"<p><p>Oxidative stress (OS) in the airway epithelium is associated with cell damage, inflammation, and mitochondrial dysfunction that may initiate or worsen respiratory disease. However, it is unclear whether exogenous antioxidants can provide protection to the airway epithelium from OS. Resveratrol and astaxanthin are nutritional compounds that have shown diverse benefits including protection against OS and inflammation in various situations. The aim of this study was to examine the utility of pre-treatment with resveratrol and astaxanthin to prevent the negative effects of oxidant exposure and restore redox homeostasis in a well-differentiated epithelium grown from primary human nasal epithelial cells (NECs) at the air-liquid interface. Fully differentiated NECs were pretreated with the antioxidants for 24 hours and the cultured epithelia was subsequently exposed to hydrogen peroxide (H₂O₂) for 1 hour to induce an acute OS. Responses measured included mitochondrial reactive oxygen species (mtROS) generation, redox status (GSH/GSSG ratio), cellular ATP, and signaling pathways (SIRT1, FOXO3, p21, PINK1, PARKIN, NRF2). Following H₂O₂ exposure, mtROS production increased by 4-fold compared with control (<i>p</i><0.01) and pre-treatment with resveratrol or astaxanthin reduced this by 50% (<i>p</i><0.05). H₂O₂ exposure reduced GSH/GSSG ratio and this decline was prevented by antioxidants pre-treatment. H₂O₂ exposure caused 2.5-fold increase in p21 mRNA expression compared with control (<i>p</i><0.05), while a slight decrease in p21 mRNA expression was observed when cells were pre-treated with resveratrol or astaxanthin. Our results demonstrate that antioxidants, resveratrol, and astaxanthin were able to protect cells from an acute OS. These agents show promise that encourages further research.</p>","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"3 4","pages":"207-217"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9910318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10707073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ethanol Consumption and Sepsis: Mechanisms of Organ Damage","authors":"A. O. Silva, C. Prohaska, C. S. Ceron","doi":"10.33696/signaling.2.056","DOIUrl":"https://doi.org/10.33696/signaling.2.056","url":null,"abstract":"Alessandra Oliveira Silva1, Clare C. Prohaska2, Carla Speroni Ceron3* 1Departamento de Alimentos e Medicamentos, Universidade Federal de Alfenas (UNIFAL-MG), Minas Gerais, Brasil 2Division of Pulmonary, Critical Care, Occupational and Sleep Medicine, Indiana University, Indianapolis, IN, USA 3Departamento de Ciências Biológicas, Universidade Federal de Ouro Preto (UFOP), Minas Gerais, Brasil *Correspondence should be addressed to Carla Speroni Ceron; carla.ceron@ufop.edu.br","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81210113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aberrant Signaling Pathways in Cancer Cells: Application of Nanomaterials","authors":"","doi":"10.33696/signaling.2.061","DOIUrl":"https://doi.org/10.33696/signaling.2.061","url":null,"abstract":"Several signaling pathways trigger normal cellular activities. Few membrane proteins such as receptor tyrosine kinases (RTKs) bind extracellular messenger molecules such as hormones or growth factors (called ligands) and undergo a conformational change relaying the signal across the membrane to the receptor’s cytoplasmic domain. Subsequently, the membrane-bound protein is activated (by phosphorylation), for example, Ras in its active GTP-bound state. GTPase-activating proteins such as neurofibromin-1 (NF-1) deactivate (dephosphorylation) Ras by converting it to an inactive GDP-bound state. The activated protein interacts with several downstream effectors initiating cascades of enzymic activities through one of the pathways to regulate cellular activities, like cell division and growth, repair of damaged DNA, glycolysis, and apoptosis [2,3]. Dysregulation in these signal transduction pathways boons the cell’s capacity to proliferate independently of exogenous growthpromoting or growth-inhibitory signals, invade surrounding tissues and metastasize to distant sites, to resist apoptosis and other forms of cell death, metabolic activities in hypoxia, sustain with genetic instability, and to induce angiogenesis [4]. Proteins associated with these dysregulated pathways are currently under investigation as possible targets of various drugs to develop cancer therapy. In this article, we have reviewed three cell signaling pathways triggered by Ras and Wnt proteins and the NF-2 genes in connection with different Abstract","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"115 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78725327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ZBP1, a dsRNA Sensor for Cell Death and Inflammation","authors":"W. Mo, Jiahuai Han","doi":"10.33696/signaling.2.057","DOIUrl":"https://doi.org/10.33696/signaling.2.057","url":null,"abstract":"TNFs promote programmed cell death (PCD), including apoptosis and necroptosis under certain circumstance [14]. Evidence showed that TNF-induced cell death is the pathology of certain inflammatory diseases [4]. However, some inflammation caused by cell death are TNF-independent. Recently, several groups reported that ZBP1, once thought to be a DNA sensor, triggers PCD and inflammation upon virus infection or endogenous retrovirus activation [5-8]. Understanding the pathologic role of ZBP1 may contribute to the treatment of incurable inflammation in clinic.","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89234648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Guanylin Peptides Signaling: Insights into Guanylate Cyclase C Dependent and Independent Signaling Pathways","authors":"Ivan Strinić, Nikola Habek, Aleksandra Dugandžić","doi":"10.33696/signaling.2.059","DOIUrl":"https://doi.org/10.33696/signaling.2.059","url":null,"abstract":"Guanylin peptides (GPs), guanylin (GN) and uroguanylin (UGN) belong to the family of natriuretic peptides (NPs), which includes atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP). NPs activate membrane guanylate cyclases (GC), also called particulate GCs, and lead to the production of their second messenger cyclic guanosine monophosphate (cGMP), which acts on cGMP dependent protein kinases (PKG), cGMPregulated phosphodiesterases (PDE) and cGMP–gated channels.","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90384209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-tumor Mechanisms of Short-chain Fatty Acids, and the Relationship between the Gut Microbiome, Carcinogenesis, Tumor Growth, and Proliferation in Colorectal Carcinoma","authors":"T. Ohara, Y. Taki","doi":"10.33696/signaling.2.060","DOIUrl":"https://doi.org/10.33696/signaling.2.060","url":null,"abstract":"Short-chain fatty acids (SCFAs) produced by the gut microbiome have been reported to have anti-tumor effects in several experimental systems [1-3]. Previously, we investigated the inhibitory effects of SCFAs (butyric acid, isobutyric acid, and acetic acid) on cell growth and proliferation in cultured human colorectal carcinoma (CRC) cell lines (DLD-1 cells, WirDr cells), and found that butyric acid displayed the strongest inhibitory effect [4]; however, the underlying mechanisms have not yet been elucidated. To investigate the anti-tumor mechanisms of SCFAs, we performed an in silico analysis of their inhibitory mechanism on tumor cell growth and proliferation in an experimental system in which SCFAs were added to cultured human CRC cell lines [5]; the results revealed that SCFAs suppress genes and transcription factors that participate in tumor cell growth, proliferation, and turnover, but do not affect genes involved in carcinogenesis, or genomes and factors associated with carcinogenic pathways.","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91080265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Treatments Targeting the Dysregulated Cell Signaling Pathway during Sepsis.","authors":"Justin H Franco, Xiaohuan Chen, Zhixing K Pan","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Previously characterized as a purely immune mediated disease, sepsis is now recognized as a dysregulated multisystem response against a pathogen. Recognition of the infectious agent by pathogen recognition receptors (PRRs) can initiate activation of the NF-κB signaling pathway and promote the secretion of proinflammatory cytokines. During sepsis, the activation of NF-κB is dysregulated and results in cytokine storm, or the pathologic release of cytokines. Current treatments for sepsis rely on broad spectrum antimicrobial medications and fluid replacement therapy, to neutralize the inciting pathogen and maintain adequate blood pressure. The addition of vasopressor therapy is also utilized when sepsis progresses to septic shock, which is defined by treatment resistant hypotension. Even though modern treatment guidelines have improved clinical outcomes, the mortality rate of sepsis and septic shock is still 15-20% and 20-50%, respectively. To reduce mortality, recent sepsis treatment research has focused on investigating novel therapeutics that can attenuate the dysregulated NF-κB signaling pathway. Antioxidants, such as Retinoic acid and Oxytocin, can reduce activation of the NF-κB pathway by neutralizing stimulatory reactive oxygen species (ROS). Likewise, anti-inflammatory agents can also affect the NF-κB pathway by decreasing the secretion of proinflammatory cytokines, such as TNFα and IL-6. Novel anti-inflammatory cytokines, such as IL-37 and IL-38, have recently been characterized and shown to reduce inflammation in mice with bacterial sepsis. Separately, antioxidants and anti-inflammatory cytokines show promise as potential therapies for sepsis, however, a combined therapy including both agents may prove more beneficial in further improving clinical outcomes.</p>","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"2 4","pages":"228-234"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8725530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39665795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic IL-1 Exposed AR⁺ PCa Cell Lines Show Conserved Loss of IL-1 Sensitivity and Evolve Both Conserved and Unique Differential Gene Expression Profiles.","authors":"Shayna E Thomas-Jardin,&nbsp;Mohammed S Kanchwala,&nbsp;Haley Dahl,&nbsp;Vivian Liu,&nbsp;Rohan Ahuja,&nbsp;Reshma Soundharrajan,&nbsp;Nicole Roos,&nbsp;Sydney Diep,&nbsp;Amrit Sandhu,&nbsp;Chao Xing,&nbsp;Nikki A Delk","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Introduction: </strong>Inflammation drives prostate cancer (PCa) progression. While inflammation is a cancer hallmark, the underlying mechanisms mediating inflammation-induced PCa are still under investigation. Interleukin-1 (IL-1) is an inflammatory cytokine that promotes cancer progression, including PCa metastasis and castration resistance. We previously found that acute IL-1 exposure represses PCa <i>androgen receptor</i> (<i>AR</i>) expression concomitant with the upregulation of pro-survival proteins, causing <i>de novo</i> accumulation of castration-resistant PCa cells. However, acute inflammation is primarily anti-tumorigenic, while chronic inflammation is pro-tumorigenic. Thus, using the LNCaP PCa cell line as model, we found that PCa cells can evolve insensitivity to chronic IL-1 exposure, restoring AR and AR activity and acquiring castration resistance. In this paper we expanded our chronic IL-1 model to include the MDA-PCa-2b PCa cell line to investigate the response to acute versus chronic IL-1 exposure and to compare the gene expression patterns that evolve in the LNCaP and MDA-PCa-2b cells chronically exposed to IL-1.</p><p><strong>Methods: </strong>We chronically exposed MDA-PCa-2b cells to IL-1α or IL-1β for several months to establish sublines. Once established, we determined subline sensitivity to exogenous IL-1 using cell viability assay, RT-qPCR and western blot. RNA sequencing was performed for parental and subline cells and over representation analysis (ORA) for geneset enrichment of biological process/pathway was performed.</p><p><strong>Results: </strong>MDA-PCa-2b cells repress AR and AR activity in response to acute IL-1 exposure and evolve insensitivity to chronic IL-1 exposure. While cell biological and molecular response to acute IL-1 signaling is primarily conserved in LNCaP and MDA-PCa-2b cells, including upregulation of NF-κB signaling and downregulation of cell proliferation, the LNCaP and MDA-PCa-2b cells evolve conserved and unique molecular responses to chronic IL-1 signaling that may promote or support tumor progression.</p><p><strong>Conclusions: </strong>Our chronic IL-1 subline models can be used to identify underlying molecular mechanisms that mediate IL-1-induced PCa progression.</p>","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"2 4","pages":"248-260"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8725614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39665796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic IL-1 Exposed AR+ PCa Cell Lines Show Conserved Loss of IL-1 Sensitivity and Evolve Both Conserved and Unique Differential Gene Expression Profiles","authors":"S. E. Thomas-Jardin, M. Kanchwala, Haley Dahl, Vivian M Liu, Rohan Ahuja, Reshma Soundharrajan, Nicole Roos, Sydney Diep, Amrit Sandhu, Chao Xing, N. Delk","doi":"10.33696/signaling.2.058","DOIUrl":"https://doi.org/10.33696/signaling.2.058","url":null,"abstract":"Introduction: Inflammation drives prostate cancer (PCa) progression. While inflammation is a cancer hallmark, the underlying mechanisms mediating inflammation-induced PCa are still under investigation. Interleukin-1 (IL-1) is an inflammatory cytokine that promotes cancer progression, including PCa metastasis and castration resistance. We previously found that acute IL-1 exposure represses PCa androgen receptor (AR) expression concomitant with the upregulation of pro-survival proteins, causing de novo accumulation of castration-resistant PCa cells. However, acute inflammation is primarily anti-tumorigenic, while chronic inflammation is pro-tumorigenic. Thus, using the LNCaP PCa cell line as model, we found that PCa cells can evolve insensitivity to chronic IL-1 exposure, restoring AR and AR activity and acquiring castration resistance. In this paper we expanded our chronic IL-1 model to include the MDA-PCa-2b PCa cell line to investigate the response to acute versus chronic IL-1 exposure and to compare the gene expression patterns that evolve in the LNCaP and MDA-PCa-2b cells chronically exposed to IL-1. Methods: We chronically exposed MDA-PCa-2b cells to IL-1α or IL-1β for several months to establish sublines. Once established, we determined subline sensitivity to exogenous IL-1 using cell viability assay, RT-qPCR and western blot. RNA sequencing was performed for parental and subline cells and over representation analysis (ORA) for geneset enrichment of biological process/pathway was performed. Results: MDA-PCa-2b cells repress AR and AR activity in response to acute IL-1 exposure and evolve insensitivity to chronic IL-1 exposure. While cell biological and molecular response to acute IL-1 signaling is primarily conserved in LNCaP and MDA-PCa-2b cells, including upregulation of NF-κB signaling and downregulation of cell proliferation, the LNCaP and MDA-PCa-2b cells evolve conserved and unique molecular responses to chronic IL-1 signaling that may promote or support tumor progression. Conclusions: Our chronic IL-1 subline models can be used to identify underlying molecular mechanisms that mediate IL-1-induced PCa progression.","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"2 1","pages":"248 - 260"},"PeriodicalIF":0.0,"publicationDate":"2021-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81328669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Treatments Targeting the Dysregulated Cell Signaling Pathway during Sepsis","authors":"Justin H. Franco, Xiaohuan Chen, Z. Pan","doi":"10.33696/signaling.2.055","DOIUrl":"https://doi.org/10.33696/signaling.2.055","url":null,"abstract":"Previously characterized as a purely immune mediated disease, sepsis is now recognized as a dysregulated multisystem response against a pathogen. Recognition of the infectious agent by pathogen recognition receptors (PRRs) can initiate activation of the NF-κB signaling pathway and promote the secretion of proinflammatory cytokines. During sepsis, the activation of NF-κB is dysregulated and results in cytokine storm, or the pathologic release of cytokines. Current treatments for sepsis rely on broad spectrum antimicrobial medications and fluid replacement therapy, to neutralize the inciting pathogen and maintain adequate blood pressure. The addition of vasopressor therapy is also utilized when sepsis progresses to septic shock, which is defined by treatment resistant hypotension. Even though modern treatment guidelines have improved clinical outcomes, the mortality rate of sepsis and septic shock is still 15–20% and 20–50%, respectively. To reduce mortality, recent sepsis treatment research has focused on investigating novel therapeutics that can attenuate the dysregulated NF-κB signaling pathway. Antioxidants, such as Retinoic acid and Oxytocin, can reduce activation of the NF-κB pathway by neutralizing stimulatory reactive oxygen species (ROS). Likewise, anti-inflammatory agents can also affect the NF-κB pathway by decreasing the secretion of proinflammatory cytokines, such as TNFα and IL-6. Novel anti-inflammatory cytokines, such as IL-37 and IL-38, have recently been characterized and shown to reduce inflammation in mice with bacterial sepsis. Separately, antioxidants and anti-inflammatory cytokines show promise as potential therapies for sepsis, however, a combined therapy including both agents may prove more beneficial in further improving clinical outcomes.","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"4 1","pages":"228 - 234"},"PeriodicalIF":0.0,"publicationDate":"2021-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81019542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}