Advances in biological regulation最新文献

{"title":"Characterisation of molecular mechanisms for PLCγ2 disease-linked variants.","authors":"Tom D Bunney, Charis Kampyli, Ashley Gregory, Matilda Katan","doi":"10.1016/j.jbior.2024.101053","DOIUrl":"https://doi.org/10.1016/j.jbior.2024.101053","url":null,"abstract":"<p><p>The phospholipase C enzyme PLCγ2 is best characterised in the context of immune cell regulation. Furthermore, many mutations discovered in PLCγ2 have been linked to the development of complex immune disorders as well as resistance to ibrutinib treatment in chronic lymphocytic leukaemia. Importantly, it has also been found that a rare variant of PLCγ2 (P522R) has a protective role in Alzheimer's disease (AD). Despite initial characterisation of these disease-linked variants, a comprehensive understanding of their differences and underpinning molecular mechanisms, needed to facilitate therapeutic efforts, is lacking. Here, we used available structural insights for PLCγ enzymes to further analyse PLCγ2 M1141K mutation, representative for mutations in immune disorders and cancer resistance, and the AD-protective variant, PLCγ2 P522R. Together with several other mutations in the autoinhibitory interface, the PLCγ2 M1141K mutation was strongly activating in a cell-based assay, under basal and stimulated conditions. Measurements of PLC activity in various in vitro assays demonstrated enhanced activity of PLCγ2 M1141K while the activity of PLCγ2 P522R was not significantly different from the WT. Similar trends were observed in several other assays, including direct liposome binding. However, an enhanced rate of phosphorylation of a functionally important tyrosine by Btk in vitro was observed for PLCγ2 P522R variants. To further assess implications of these in vitro findings in a cellular context relevant for the PLCγ2 P522R variant, microglia (BV2) stable cell lines were generated and analysed under growth conditions. The PLC activity in cells expressing PLCγ2 P522R at physiologically relevant levels was clearly enhanced compared to the WT, and differences in cell morphology observed. These data, combined with the structural insights, suggest that the PLCγ2 P522R variant has subtle, localised structural changes that do not directly affect the PLC activity by compromising autoinhibition, as determined for PLCγ2 M1141K. It is also likely that in contrast to the PLCγ2 M1141K, the functional impact of the P522R substitution completely depends on further interactions with upstream kinases and other regulatory proteins in a relevant cellular context, where changes in the PLCγ2 P522R variant could facilitate processes such as phosphorylation and protein-protein interactions.</p>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142306937","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":"Label-free live characterization of mesenchymal stem cell spheroids by biophysical properties measurement","authors":"","doi":"10.1016/j.jbior.2024.101052","DOIUrl":"10.1016/j.jbior.2024.101052","url":null,"abstract":"<div><p>Three-dimensional (3D) cell culture has become a consolidated method in the stem cell field, where mesenchymal stromal stem cells (MSCs) can be used to generate <em>in vitro</em> spheroid aggregates called MSC-Spheroids (MSph). MSph is a floating cluster of stem cells similar to those in literature are known as bone marrow-derived “mesenspheres”. Even though MSC properties are shared by MSph, depending on the cell type and their tissue source, the morphology and degree of compaction of the MSph can be variable, creating limitations in such a cell model. Thus, during culture, a variation in stem cell functionality and viability, in addition to the suitability for comparing MSph in some experimental protocols, can be affected by spheroid biophysical intrinsic properties like mass density. To investigate this limitation and provide a new method for researchers, MSph of seven different tissue sources were compared by combining mass density, weight, and size evaluations with viability assays for ATP measurement. MSph cultured in traditional static conditions showed decreased in viability over the days of culture, while mass density exhibited different trends among cell types. Additionally, treatment of MSph with a non-toxic concentration of a natural compound cell regulator, such as plumbagin, altered the mass density of a selected cell type, thereby confirming the efficacy of the biophysical approach in monitoring MSph variability post-treatment. The results encourage using MSph in the early days of culture after their formation to ensure viability and likely retention of the stem cell phenotype.</p></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S221249262400040X/pdfft?md5=36840907f04b93a185dcc4f92bc58052&pid=1-s2.0-S221249262400040X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142240244","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":"Epigenetic modulation of immune cells: Mechanisms and implications","authors":"","doi":"10.1016/j.jbior.2024.101043","DOIUrl":"10.1016/j.jbior.2024.101043","url":null,"abstract":"<div><div>Epigenetic modulation of the immune response entails modifiable and inheritable modifications that do not modify the DNA sequence. While there have been many studies on epigenetic changes in tumor cells, there is now a growing focus on epigenetically mediated changes in immune cells of both the innate and adaptive systems. These changes have significant implications for both the body's response to tumors and the development of potential therapeutic vaccines. This study primarily discusses the key epigenetic alterations, with a specific emphasis on pseudouridination, as well as non-coding RNAs and their transportation, which can lead to the development of cancer and the acquisition of new phenotypic traits by immune cells. Furthermore, the advancement of therapeutic vaccinations targeting the tumor will be outlined.</div></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278750","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":"Impact of cellular ATP levels on cell viability in response to fluorouracil through lysophosphatidic acid (LPA) receptor-4 (LPA4) and LPA6 in colon cancer cells","authors":"","doi":"10.1016/j.jbior.2024.101042","DOIUrl":"10.1016/j.jbior.2024.101042","url":null,"abstract":"<div><p>Lysophosphatidic acid (LPA) signaling via LPA receptors (LPA₁ to LPA₆) mediates various aspects of cancer cell behaviors. This study aimed to investigate the variation in intracellular ATP levels and its impact on cell viability in response to fluorouracil (5-FU) through LPA₄ and LPA₆ in colon cancer DLD-1 cells. LPA₄ and LPA₆ are linked to Gs and Gi proteins. Gs protein stimulates the activity of adenylyl cyclase, which catalyzes the conversion of ATP to cAMP, whereas Gi protein inhibits this activity. In cell survival assay, cells were treated with 5-FU every 24 h for 3 days. The viability in response to 5-FU in DLD-1 cells was enhanced by LPA₄ and LPA₆ knockdowns. Furthermore, LPA₄ and LPA₆ knockdowns reduced the expression of cleaved-PARP1 protein when cells were treated with 5-FU. Since ethidium bromide (EtBr) reduces mitochondrial DNA level in cultured cells, EtBr-treated (DLD-EtBr) cells were generated from DLD-1 cells. The viability to 5-FU in DLD-EtBr cells was higher than that of DLD-1 cells. Additionally, culturing DLD-1 cells in a low glucose-containing medium led to increased viability to 5-FU. <em>LPAR4</em> and <em>LPAR6</em> expressions were reduced in both DLD-EtBr and low glucose-treated cells. The cellular ATP levels were significantly decreased in DLD-1 cells following EtBr treatment and exposure to low glucose conditions. Conversely, in the presence of LPA, LPA₄ and LPA₆ knockdowns resulted in a marked elevation of ATP levels. These results suggest that cell viability to 5-FU is negatively regulated via the activation of LPA₄-and LPA₆-Gs protein pathways in DLD-1 cells rather than Gi protein.</p></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141639069","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":"Advancements in unravelling the fundamental function of the ATAD3 protein in multicellular organisms","authors":"Divya Goel ,&nbsp;Sudhir Kumar","doi":"10.1016/j.jbior.2024.101041","DOIUrl":"https://doi.org/10.1016/j.jbior.2024.101041","url":null,"abstract":"<div><p>ATPase family AAA domain containing protein 3, commonly known as ATAD3 is a versatile mitochondrial protein that is involved in a large number of pathways. ATAD3 is a transmembrane protein that spans both the inner mitochondrial membrane and outer mitochondrial membrane. It, therefore, functions as a connecting link between the mitochondrial lumen and endoplasmic reticulum facilitating their cross-talk. ATAD3 contains an N-terminal domain which is amphipathic in nature and is inserted into the membranous space of the mitochondria, while the C-terminal domain is present towards the lumen of the mitochondria and contains the ATPase domain. ATAD3 is known to be involved in mitochondrial biogenesis, cholesterol transport, hormone synthesis, apoptosis and several other pathways. It has also been implicated to be involved in cancer and many neurological disorders making it an interesting target for extensive studies. This review aims to provide an updated comprehensive account of the role of ATAD3 in the mitochondria especially in lipid transport, mitochondrial-endoplasmic reticulum interactions, cancer and inhibition of mitophagy.</p></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141438616","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":"Decoding how receptor tyrosine kinases (RTKs) mediate nuclear calcium signaling","authors":"María José González Armijos,&nbsp;Thais Fernandes Bassani,&nbsp;Clara Couto Fernandez,&nbsp;Michele Angela Rodrigues ,&nbsp;Dawidson Assis Gomes","doi":"10.1016/j.jbior.2024.101033","DOIUrl":"https://doi.org/10.1016/j.jbior.2024.101033","url":null,"abstract":"<div><p>Calcium (Ca²⁺) is a highly versatile intracellular messenger that regulates several cellular processes. Although it is unclear how a single-second messenger coordinates various effects within a cell, there is growing evidence that spatial patterns of Ca²⁺ signals play an essential role in determining their specificity. Ca²⁺ signaling patterns can differ in various cell regions, and Ca²⁺ signals in the nuclear and cytoplasmic compartments have been observed to occur independently. The initiation and function of Ca²⁺ signaling within the nucleus are not yet fully understood. Receptor tyrosine kinases (RTKs) induce Ca²⁺ signaling resulting from phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolysis and inositol 1,4,5-trisphosphate (InsP3) formation within the nucleus. This signaling mechanism may be responsible for the effects of specific growth factors on cell proliferation and gene transcription. This review highlights the recent advances in RTK trafficking to the nucleus and explains how these receptors initiate nuclear calcium signaling.</p></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140914063","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":"The potential of the nutraceutical berberine in the treatment of hepatocellular carcinoma and other liver diseases such as NAFLD and NASH","authors":"Melchiorre Cervello ,&nbsp;Giuseppa Augello ,&nbsp;Lucio Cocco ,&nbsp;Stefano Ratti ,&nbsp;Matilde Y. Follo ,&nbsp;Alberto M. Martelli ,&nbsp;Antonella Cusimano ,&nbsp;Giuseppe Montalto ,&nbsp;James A. McCubrey","doi":"10.1016/j.jbior.2024.101032","DOIUrl":"10.1016/j.jbior.2024.101032","url":null,"abstract":"<div><p>Hepatocellular carcinoma (HCC) is a common cancer which unfortunately has poor outcomes. Common anti-cancer treatments such as chemotherapy and targeted therapy have not increased patient survival significantly. A common treatment for HCC patients is transplantation, however, it has limitations and complications. Novel approaches are necessary to more effectively treat HCC patients. Berberine (BBR) is a nutraceutical derived from various fruits and trees, which has been used for centuries in traditional medicine to treat various diseases such as diabetes and inflammation. More recently, the anti-proliferation effects of BBR have been investigated in the treatment of patients with various cancers, especially colorectal cancer, and in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). In this review, we will focus on studies with BBR in liver diseases.</p></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140781819","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":"Lysophosphatidic acid (LPA) receptor-mediated signaling and cellular responses to anticancer drugs and radiation of cancer cells","authors":"Hiroko Ikeda,&nbsp;Miwa Takai,&nbsp;Toshifumi Tsujiuchi","doi":"10.1016/j.jbior.2024.101029","DOIUrl":"10.1016/j.jbior.2024.101029","url":null,"abstract":"<div><p>Lysophosphatidic acid (LPA) is a simple physiological lipid and structurally consists of a fatty, a phosphate and a glycerol. LPA binds to G protein-coupled LPA receptors (LPA₁ to LPA₆). LPA receptor-mediated signaling mediates a variety of biological responses, such as cell growth, migration, morphogenesis, differentiation and protection from apoptosis. It is considered that LPA receptor-mediated signaling plays an important role in the pathogenesis of human malignancies. So far, genetic and epigenetic alterations of LPA receptors have been found in several cancer cells as well as abnormal LPA production. In addition, LPA receptor-mediated signaling regulates the promotion of malignant behaviors, including chemo- and/or radiation-resistance. Chemotherapy and radiotherapy are the common approaches to the treatments of cancers. However, resistance to anticancer drugs and irradiation is the most critical limitation for chemotherapy and radiotherapy. In this review, we provide the roles of LPA receptor-mediated signaling in the regulation of cellular responses induced by chemotherapeutic agents and irradiation and its biological utility as a possible molecular target for improving cancer cell responses to chemotherapy and radiotherapy.</p></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139830187","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":"A new method for quantifying the enzyme activity of DGKs","authors":"Millie Xin Barbernitz ,&nbsp;Daniel M. Raben","doi":"10.1016/j.jbior.2023.100998","DOIUrl":"10.1016/j.jbior.2023.100998","url":null,"abstract":"<div><p>Diacylglycerol kinases (DGKs) are a family of enzymes that catalyze the ATP-dependent conversion of diacylglycerol (DAG) to phosphatidic acid (PtdOH). A common approach to examine the activity of these enzymes relys on a radiometric assay (Epand and Topham, 2007; Tu-Sekine and Raben, 2017). This assay quantifies the DGK-catalyzed incorporation of ³²P into DAG from AT³²P to generate ³²PtdOH and is perhaps been the most widely used assay. While sensitive, its drawbacks are the expense and the potential negative impacts on health and the environment. In this report, we describe a new assay which utilizes fluorescent labeled NBD-DAG (1-Oleoyl-2-[12-[(7-nitro-2-1,3-benzoxadiazol-4-yl) amino] dodecanoyl]-sn-Glycero-3-diacylglycerol) to quantify the DGK-θ-catalyzed conversion of NBD-DAG to NBD-PtdOH. Furthermore, we show the assay is sufficiently sensitive as the measured specific activity was similar to that previously determined with AT³²P (Tu-Sekine and Raben, 2012) and was able to detect the activation of DGK-θ by synaptotagmin-1 (Barber et al., 2022). Overall, this assay is inexpensive, sensitive, and reproducible making it an attractive alternative to currently established assays.</p></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135566034","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":"Biology of childhood hepatoblastoma and the search for novel treatments","authors":"Marjut Pihlajoki ,&nbsp;Katja Eloranta ,&nbsp;Ruth Nousiainen ,&nbsp;Ville Väyrynen ,&nbsp;Tea Soini ,&nbsp;Antti Kyrönlahti ,&nbsp;Seppo Parkkila ,&nbsp;Jukka Kanerva ,&nbsp;David B. Wilson ,&nbsp;Mikko P. Pakarinen ,&nbsp;Markku Heikinheimo","doi":"10.1016/j.jbior.2023.100997","DOIUrl":"10.1016/j.jbior.2023.100997","url":null,"abstract":"<div><p>Our research laboratory has a longstanding interest in developmental disorders and embryonic tumors, and recent efforts have focused on the pathogenesis of pediatric liver tumors. This review focuses on hepatoblastoma (HB), the most common pediatric liver malignancy. Despite advances in treatment, patients with metastatic HB have a poor prognosis, and survivors often have permanent side effects attributable to chemotherapy. In an effort to improve survival and lessen long-term complications of HB, we have searched for novel molecular vulnerabilities using a combination of patient derived cell lines, metabolomics, and RNA sequencing of human samples at diagnosis and follow-up. These studies have shed light on pathogenesis and identified putative targets for future therapies in children with advanced HB.</p></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S221249262300043X/pdfft?md5=7d1cb69691b41ae0282774274077ed6c&pid=1-s2.0-S221249262300043X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136093654","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}