Journal of cellular signaling最新文献

{"title":"Function of Mitogen-Activated Protein Kinases in Hepatic Inflammation.","authors":"Gabrielle Westenberger,&nbsp;Jacob Sellers,&nbsp;Savanie Fernando,&nbsp;Sadie Junkins,&nbsp;Sung Min Han,&nbsp;Kisuk Min,&nbsp;Ahmed Lawan","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The western diet and overuse of anti-inflammatory medication have caused a great deal of stress on the liver. Obesity and the associated inflammatory state in insulin-responsive tissues result in the release of pro-inflammatory cytokine that activates the stress-responsive MAPKs, p38 MAPK, and JNK. These MAPKs have figured prominently as critical effectors in physiological and pathophysiological hepatic inflammation. In contrast, evidence for a role for ERK1/2 in hepatic inflammation has been less well developed. In this review article, we describe recent insights into the physiology and pathophysiology of the role of stress-responsive MAPKs in hepatic inflammation during obesity and liver injury with a focus on macrophages, hepatocytes and hepatic stellate cells. In response to metabolic stress and liver injury, JNK activation in macrophages and hepatocytes promotes the secretion of inflammatory cytokines and macrophage and neutrophil infiltration. p38 MAPK plays an important role in contributing to the progression of hepatic inflammation in response to various hepatic cellular stresses, although the precise substrates mediating these effects in hepatocytes and hepatic stellate cells remain to be identified. Both JNK and p38 MAPK promotes profibrotic behavior in hepatic stellate cells.</p>","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"2 3","pages":"172-180"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8457364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39444374","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":"S1P Generation by Sphingosine Kinase-2 in Recruited Macrophages Resolves Lung Inflammation by Blocking STING Signaling in Alveolar Macrophages.","authors":"Jagdish C Joshi,&nbsp;Bhagwati Joshi,&nbsp;Ian Rochford,&nbsp;Dolly Mehta","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Acute respiratory distress syndrome (ARDS) is the major cause of mortality among hospitalized acute lung injury (ALI) patients. Lung macrophages play an important role in maintaining the tissue-fluid homeostasis following injury. We recently showed that circulating monocytes recruited into the alveolar space suppressed the stimulator of type 1 interferon genes (STING) signaling in alveolar macrophages through sphingosine-1-phosphate (S1P). We used CD11b-DTR mice to deplete CD11b⁺ monocytes following LPS or <i>Pseudomonas aeruginosa</i> infection. Depletion of CD11b⁺ monocytes leads to the persistent inflammatory injury, infiltration of neutrophils, activation of STING signaling and mortality following lung infection. We demonstrated that adoptively transferred SPHK2-CD11b⁺ monocytes into CD11b-DTR mice after pathogenic infection rescue lung inflammatory injury.</p>","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"2 1","pages":"47-51"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25414971","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":"APE1/Ref-1 - One Target with Multiple Indications: Emerging Aspects and New Directions.","authors":"Mahmut Mijit,&nbsp;Rachel Caston,&nbsp;Silpa Gampala,&nbsp;Melissa L Fishel,&nbsp;Jill Fehrenbacher,&nbsp;Mark R Kelley","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In the realm of DNA repair, base excision repair (BER) protein, APE1/Ref-1 (Apurinic/Apyrimidinic Endonuclease 1/Redox Effector - 1, also called APE1) has been studied for decades. However, over the past decade, APE1 has been established as a key player in reduction-oxidation (redox) signaling. In the review by Caston <i>et al.</i> (<i>The multifunctional APE1 DNA repair-redox signaling protein as a drug target in human disease),</i> multiple roles of APE1 in cancer and other diseases are summarized. In this Review, we aim to expand on the contributions of APE1 to various diseases and its effect on disease progression. In the scope of cancer, more recent roles for APE1 have been identified in cancer cell metabolism, as well as chemotherapy-induced peripheral neuropathy (CIPN) and inflammation. Outside of cancer, APE1 signaling may be a critical factor in inflammatory bowel disease (IBD) and is also an emergent area of investigation in retinal ocular diseases. The ability of APE1 to regulate multiple transcription factors (TFs) and therefore multiple pathways that have implications outside of cancer, makes it a particularly unique and enticing target. We discuss APE1 redox inhibitors as a means of studying and potentially combating these diseases. Lastly, we examine the role of APE1 in RNA metabolism. Overall, this article builds on our previous review to elaborate on the roles and conceivable regulation of important pathways by APE1 in multiple diseases.</p>","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"2 3","pages":"151-161"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8457357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39444375","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":"Wnt Signaling Cascades and Their Role in Coronary Artery Health and Disease.","authors":"Nadisha Weerackoon,&nbsp;Kushan L Gunawardhana,&nbsp;Arya Mani","doi":"10.33696/Signaling.2.035","DOIUrl":"https://doi.org/10.33696/Signaling.2.035","url":null,"abstract":"<p><p>The Wnt signaling is classified as two distinct pathways of canonical Wnt/β-catenin signaling, and the non-canonical pathways of planar cell polarity and Wnt/Ca²⁺ pathways. However, the scientific discoveries in recent years have shown that canonical and non-canonical Wnts pathways are intertwined and have complex interaction with other major signaling pathways such as hedgehog, Hippo and TOR signaling. Wnt signaling plays important roles in cell proliferation, differentiation and migration during embryonic development. The impairment of these pathways during embryonic development often leads to major congenital defects. In adult organisms Wnt expression is more restricted to proliferating tissues, where it plays a key role in tissue regeneration. In addition, the disruption of homeostatic processes of multicellular organisms may give rise to reactivation and/or altered activation of Wnt signaling, leading to development of malignant tumors and chronic diseases such as type-2 diabetes and adult cardiovascular diseases. Coronary artery disease (CAD) is the leading cause of death in the world. The disease is the consequences of two distinct disease processes: Atherosclerosis, a primarily inflammatory disease and plaque erosion, a disease process associated with endothelial cell defect and smooth muscle proliferation with only modest contribution of inflammatory cells. The atherosclerosis is itself a multifactorial disease that is initiated by lipid deposition and endothelial dysfunction, triggering vascular inflammation via recruitment and aggregation of monocytes and their transformation to foam cell by the uptake of modified low-density lipoprotein (LDL), culminating in an atheromatous plaque core formation. Further accumulation of lipids, infiltration and proliferation of vascular smooth muscle cells (VSMCs) and extracellular matrix deposition result in intimal hyperplasia. Myocardial infarction is the ultimate consequence of these processes and is caused by plaque rupture and hypercoagulation. <i>In vivo</i> studies have established the role of the Wnt pathway in all phases of atherosclerosis development, though much remains unknown or controversial. Less is known about the mechanisms that induce plaque erosion. The limited evidence in mouse models of Wnt coreceptor LRP6 mutation and heterozygous TCF7L2 knock out mice implicate altered Wnt signaling also in the pathogenesis of plaque erosion. In this article we focus and review the role of the Wnt pathway in CAD pathophysiology from clinical and experimental standpoints.</p>","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"2 1","pages":"52-62"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38966274","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":"Possible Therapeutic Use of Natural Compounds Against COVID-19.","authors":"Nabab Khan, Xuesong Chen, Jonathan D Geiger","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The outbreak of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has led to coronavirus disease-19 (COVID-19); a pandemic disease that has resulted in devastating social, economic, morbidity and mortality burdens. SARS-CoV-2 infects cells following receptor-mediated endocytosis and priming by cellular proteases. Following uptake, SARS-CoV-2 replicates in autophagosome-like structures in the cytosol following its escape from endolysosomes. Accordingly, the greater endolysosome pathway including autophagosomes and the mTOR sensor may be targets for therapeutic interventions against SARS-CoV-2 infection and COVID-19 pathogenesis. Naturally existing compounds (phytochemicals) through their actions on endolysosomes and mTOR signaling pathways might provide therapeutic relief against COVID-19. Here, we discuss evidence that some natural compounds through actions on the greater endolysosome system can inhibit SARS-CoV-2 infectivity and thereby might be repurposed for use against COVID-19.</p>","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"2 1","pages":"63-79"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25517673","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":"Effects of a CB₂ Subtype Selective Agonist ABK5-1 on Cytokine Production in Microglia.","authors":"Yaliang Tang, Barbara Wolk, Debra A Kendall","doi":"10.33696/signaling.2.038","DOIUrl":"10.33696/signaling.2.038","url":null,"abstract":"<p><strong>Background and objectives: </strong>Neuroinflammation is closely associated with various diseases including neuropathic pain. Microglia are immune cells in the central nervous system which are the main players of immunity and inflammation. Since microglia are activated by nerve injury, and they produce proinflammatory mediators to cause neuropathic pain, targeting activated microglia is considered to be a strategy for treating neuropathic pain. Activation of the cannabinoid CB₂ receptor is known to have anti-inflammatory effects in microglia. ABK5-1 is a CB₂ subtype selective agonist which inhibits IL-1β and IL-6 production in the microglia cell line BV-2. The purpose of the current study is to further analyze anti-inflammatory effects of ABK5 in terms of different cytokines and the possible pathway involved in the effect in the BV-2 cell line.</p><p><strong>Methods: </strong>A cytokine array was performed to screen the effect of ABK5-1 on forty inflammatory mediators in BV-2 cells. Changes of the inflammatory mediators was further supported by mRNA analysis, and a possible signaling molecule that involved the observation was evaluated by western blot.</p><p><strong>Results: </strong>Stimulating BV-2 cells by lipopolysaccharide increased expression of eleven inflammatory mediators, and ABK5-1 treatment resulted in more than a 50% decrease of sICAM1, IL-6, and RANTES. Real-time PCR results showed a decrease of G-CSF, ICAM1, MCP-1, MIP-1α, and MIP-1β mRNA levels. Western blot analysis showed that ABK5-1 inhibited LPS-induced ERK phosphorylation, which can be a mechanism of ABK5-1-mediated anti-inflammatory effect.</p><p><strong>Conclusions: </strong>Our current results support the possibility that ABK5-1 is an anti-inflammatory drug for microglia.</p>","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"2 2","pages":"85-93"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39185138","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":"Dendorbium Nobile Lindl. Alkaloids Suppress NF-kB and NLRP3 Signaling Pathways to Attenuate Lipopolysaccharideinduced Neuroinflammation","authors":"Jiaojiao Liu, Bo Liu, Xi He, Wu Qin, Jingshan Shi","doi":"10.33696/signaling.1.019","DOIUrl":"https://doi.org/10.33696/signaling.1.019","url":null,"abstract":"Alzheimer’s disease (AD) is the most common brain disease with aging characterized by progressive memory loss and cognitive decline. The hallmark of AD is the formation of senile plaques composed of amyloid-β (Aβ) and neurofibrillary tangles (NFTs). Accumulating evidence indicates that neuroinflammation is also a critical hallmark of AD [1]. Microglia are the major regulators of neuroinflammation in mammalian brain and play a pathological role in AD development and progression [2]. Macroglia could degrade Aβ to resist its deposition, on the other hand, microglia can release proinflammatory mediators to cause neuroinflammation and aggravate Aβ and tau pathology [3-5].","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"98 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81617857","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":"Kinetin/N6-furfuryladenine: A New Neurodegenerative Disease Lead from an Old Plant Cytokine","authors":"Tamara Maiuri, R. Truant","doi":"10.33696/signaling.1.029","DOIUrl":"https://doi.org/10.33696/signaling.1.029","url":null,"abstract":"195 N6-fufuryladenine (N6FFA), or kinetin, has a long history as a plant cytokine with practical applications in agriculture. This adenosine analog is now commonplace in natural product small molecule chemical screening libraries, and as such has been discovered as active in mammalian disease pathways that include Parkinson’s disease, Huntington’s disease (HD) and Familial Dysautonomia. We provide a perspective on our data relative to HD and recent discoveries of genetic modifiers of this disease predominantly related to DNA damage repair. We outline the importance of nucleotide salvage and the presence of this adenosine analog in human samples and efficacy in models of human disease, with mechanisms that are empowered by chemical studies using N6FFA as a nucleic acid crosslinking agent.","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"54 1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89333022","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":"Galectin 3 and Glial Cells of the CNS: A Fruitful Crosstalk with Remyelinating Potential","authors":"L. Pasquini","doi":"10.33696/signaling.1.020","DOIUrl":"https://doi.org/10.33696/signaling.1.020","url":null,"abstract":"Galectins (Gals) are a group of 15 proteins characterized by a highly conserved carbohydrate-recognition domain (CRD) and made up of approximately 130 amino-acids which bind β-galactose in glycoconjugates. Gals are classified into three groups according to their structures [1-3], i.e. proto, chimera and tandem-repeat. Proto Gals, which have a single CRD, include Gal-1, Gal-2, Gal5, Gal-7, Gal-10, Gal-11, Gal-13, Gal-14, and Gal-15. In turn, tandem-repeat Gals contain two similar CRD and comprise Gal-4, Gal-6, Gal-8, Gal-9, and Gal-12. The only member of the chimera class, Gal-3 has three structural domains: (a) the NH2 terminal domain containing serine phosphorylation, important for nuclear localization, secretion and oligomerization; (b) a sequence susceptible to metalloprotease (MMP) cleavage; and (c) a C-terminal domain containing the CRD and an anti-death motif [4,5]. Worth pointing out, the N-terminal domain allows the formation of pentamers upon the interaction of Gal-3 monomers with glycoproteins or glycolipids.","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85076513","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":"NOXA the BCL-2 Family Member behind the Scenes in Cancer Treatment","authors":"Alison Dumont, Steven Lohard, L. Maillet, P. Juin, S. Barillé-Nion","doi":"10.33696/signaling.1.021","DOIUrl":"https://doi.org/10.33696/signaling.1.021","url":null,"abstract":"Apoptosis, a programmed cell death relying on the cascade activation of caspases, regulates many processes ranging from embryonic development to immune homeostasis, and plays a major role in cancer. Escape from apoptosis is indeed one of the fundamental characteristics of tumor cells that frequently exhibit increased expression of the main prosurvival BCL-2 homologues BCL-2, BCL-xL and/ or MCL-1 contributing to tumor progression or resistance to anticancer treatments [1]. Mitochondria Outer Membrane Permeabilization (MOMP) is a key cellular event in apoptosis as subsequent release of cytochrome-c (cyto-c) from the mitochondrial intermembrane space to cytosol through BAX/BAK pores, promotes apoptosome formation and downstream activation of apoptotic effector caspases. MOMP can also lead to the release of other mitochondrial components including mitochondrial DNA that engage additional inflammatory signalling pathways inhibited by apoptotic caspases [2,3]. BCL-2 family proteins tightly control BAX/BAK-dependent MOM permeability through a dynamic network of protein-protein interactions integrating various cellular stresses and finally dictating life or death decisions and cell fates [4]. Chemotherapies often upregulate expression of proapoptotic BCL-2 homologues in cancer cells, shifting by this way the balanced death/survival signals towards apoptosis as an expected cytotoxic effect. Among the proapoptotic BH3only proteins of the BCL-2 family, NOXA is unique since in preferentially inhibiting the prosurvival BCL-2 homologue MCL-1, it decreases the protective effect MCL-1 exerts on mitochondrial membranes and transfers MOM integrity surveillance and downstream prevention of caspase activation, mostly to BCL-2 and/or BCL-xL. This was observed in particular during mitotic-related stress after antimitotic treatment or during endoplasmic reticulum (ER) stress induced by proteasome inhibitors, where NOXA was shown to accumulate through transcriptional or post-translational mechanisms, as we detail in this review. Importantly, prosurvival members of BCL-2 family are Abstract","PeriodicalId":73645,"journal":{"name":"Journal of cellular signaling","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79196870","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}