Journal of cell deathPub Date : 2019-04-03eCollection Date: 2019-01-01DOI: 10.1177/1179066019836967
Elle Koren, Yaron Fuchs
{"title":"The ARTS of Cell Death.","authors":"Elle Koren, Yaron Fuchs","doi":"10.1177/1179066019836967","DOIUrl":"https://doi.org/10.1177/1179066019836967","url":null,"abstract":"<p><p>Although much is known regarding intestinal stem cell (ISC) self-renewal and differentiation, the specific mechanisms used for their elimination is unclear. We recently discovered that the pro-apoptotic protein ARTS, a <i>Septin4</i> isoform, interacts with X-linked inhibitor of apoptosis (XIAP) in the ISC niche to regulate stem cell survival during intestinal homeostasis and regeneration. These findings point to an intriguing avenue of translational research, examining how manipulation of stem cell apoptosis through the ARTS/XIAP module can affect stem-cell-dependent processes.</p>","PeriodicalId":89169,"journal":{"name":"Journal of cell death","volume":"12 ","pages":"1179066019836967"},"PeriodicalIF":0.0,"publicationDate":"2019-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179066019836967","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37151544","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":"The Effect of Transfusion-Dependent Thalassemia Patient's Serum on Peripheral Blood Mononuclear Cell Viability.","authors":"Nawapong Patpan, Ratana Banjerdpongchai, Adisak Tantiworawit, Juthathip Poofery, Phimphan Komonrit, Kanda Fanhchaksai, Thanawat Rattanathammethee, Chatree Chai-Adisaksopha, Ekarat Rattarittamrong, Lalita Norasetthada, Pimlak Charoenkwan","doi":"10.1177/1179066018823534","DOIUrl":"https://doi.org/10.1177/1179066018823534","url":null,"abstract":"<p><p>Iron overload is a major complication in transfusion-dependent thalassemia (TDT) patients. Chronic oxidative stress from iron overload may lead to cellular damage and viability. This is a cross-sectional study. Transfusion-dependent thalassemia patients aged ⩾18 years old were enrolled. Transfusion-dependent thalassemia patient's serum and normal volunteer's serum were separately incubated with healthy peripheral blood mononuclear cells (PBMCs). The cell viability was measured by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay at 24, 48, and 72 hours. Sixty-nine TDT patients and 22 healthy controls were enrolled. The mean of PBMCs viability after incubation with serum from TDT patients was lower than that with the controls (88.65% vs 103.56% at 24 hours, 78.77% vs 112.04%% at 48 hours, and 71.18% vs 132.16%% at 72 hours, respectively). High serum ferritin level (correlation -0.29, <i>P</i> < .05) and white blood cell (WBC) count negatively affected cell viability (correlation -2.86, <i>P</i> = .05). From multivariate analysis, serum ferritin level is the only significant risk factor that is independently associated with cell viability (correlation -11.42, <i>P</i> < .001). Our findings showed that TDT patient's serum causes decreased cell viability. Serum ferritin level was a significant independent factor influencing cell viability.</p>","PeriodicalId":89169,"journal":{"name":"Journal of cell death","volume":"12 ","pages":"1179066018823534"},"PeriodicalIF":0.0,"publicationDate":"2019-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179066018823534","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36877456","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}
Journal of cell deathPub Date : 2018-11-05eCollection Date: 2018-01-01DOI: 10.1177/1179066018809091
Nour S Erekat
{"title":"Cerebellar Upregulation of Cell Surface Death Receptor-Mediated Apoptotic Factors in Harmaline-Induced Tremor: An Immunohistochemistry Study.","authors":"Nour S Erekat","doi":"10.1177/1179066018809091","DOIUrl":"https://doi.org/10.1177/1179066018809091","url":null,"abstract":"<p><p>Active caspase-3-mediated apoptosis has been implicated in the pathogenesis of harmaline-induced tremor. The aim of this study is to illustrate the impact of tremor induction on the expression of factors mediating the cell surface death receptor-dependent apoptosis. A total of 20 normal Wistar rats were randomly selected and equally divided into control and experimental groups. Tremor was induced in the experimental group by injecting the rats with a single dose of harmaline (50 mg/kg). After that, cerebellar tissues were evaluated by immunohistochemistry to examine the expression of tumor necrosis factor α (TNF-α) and active caspase-8 in the 2 groups of animals. TNF-α and active caspase-8 expression was significantly higher in cerebella from experimental rats compared with that in those from the control rats (<i>P</i> value < .01). Thus, our present data suggest the association of tremor induction with the cerebellar overexpression of TNF-α and active caspase-8, correlative with Purkinje cell (PC) loss indicated by loss of calbindin immunoreactivity, indicating the induction of the cell surface death receptor-mediated apoptosis.</p>","PeriodicalId":89169,"journal":{"name":"Journal of cell death","volume":"11 ","pages":"1179066018809091"},"PeriodicalIF":0.0,"publicationDate":"2018-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179066018809091","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36743066","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":"\"Programmed Cell Death: A Process of Death for Survival\" - How Far Terminology Pertinent for Cell Death in Unicellular Organisms.","authors":"Shiv Shanker Pandey, Samer Singh, Chandramani Pathak, Budhi Sagar Tiwari","doi":"10.1177/1179066018790259","DOIUrl":"https://doi.org/10.1177/1179066018790259","url":null,"abstract":"<p><p>Programmed cell death (PCD) is genetically regulated phenomenon of selective elimination of target cells that are either under pathological conditions or unwanted for organism's normal growth and development due to other reasons. The process although being genetically controlled is physiological in nature that renders some hallmarks like blebs in the cell membrane, lobe formation in nuclear membrane, DNA nicks resulting to DNA ladder of 200 bp, and downstream activation of caspases. Moreover, as the process refers to the death of \"targeted cell\", the term is exclusively suitable for multicellular organisms. Number of reports advocate similar type of cell death process in unicellular organisms. As cell death in unicellular organisms is also reflected by the signature of PCD obtained in metazoans, such cell death has been grouped under the broad category of PCD. It is pertinent to mention that by definition a unicellular organism is made of a single cell wherein it carries out all of its life processes. Using the term \"Programmed Cell Death\" with a preset \"survival strategy of the organism\" for unicellular organisms looks misnomer. Therefore, this correspondence argues and requests recommendation committee on cell death to revisit for the nomenclature of the cell death process in the unicellular organisms.</p>","PeriodicalId":89169,"journal":{"name":"Journal of cell death","volume":"11 ","pages":"1179066018790259"},"PeriodicalIF":0.0,"publicationDate":"2018-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179066018790259","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36403014","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}
Journal of cell deathPub Date : 2018-07-04eCollection Date: 2018-01-01DOI: 10.1177/1179066018785141
Nu T Lu, Natalie M Liu, Darshil Patel, James Q Vu, Lisa Liu, Chae Yeon Kim, Peter Cho, Ronik Khachatoorian, Nikita Patel, Clara E Magyar, Ekambaram Ganapathy, Vaithilingaraja Arumugaswami, Asim Dasgupta, Samuel Wheeler French
{"title":"Oncoprotein Stathmin Modulates Sensitivity to Apoptosis in Hepatocellular Carcinoma Cells During Hepatitis C Viral Replication.","authors":"Nu T Lu, Natalie M Liu, Darshil Patel, James Q Vu, Lisa Liu, Chae Yeon Kim, Peter Cho, Ronik Khachatoorian, Nikita Patel, Clara E Magyar, Ekambaram Ganapathy, Vaithilingaraja Arumugaswami, Asim Dasgupta, Samuel Wheeler French","doi":"10.1177/1179066018785141","DOIUrl":"https://doi.org/10.1177/1179066018785141","url":null,"abstract":"<p><p>Patients with chronic hepatitis C virus (HCV) infection risk complications of cirrhosis, liver failure, and hepatocellular carcinoma (HCC). Previously, our proteomic examination of hepatocytes carrying a HCV-replicon revealed that deregulation of cytoskeletal dynamics may be a potential mechanism of viral-induced HCC growth. Here, we demonstrate the effect of HCV replication on the microtubule regulator stathmin (STMN1) in HCC cells. We further explore how the altered activity or synthesis of stathmin affects cellular proliferation and sensitivity to apoptosis in control HCC cells (Huh7.5) and experimental HCV-replicon harboring HCC cells (R-Huh7.5). The HCV-replicon harboring HCC cells (R-Huh 7.5) lack viral structural genes/proteins for acute infectivity and thus is the standard model for in vitro chronic infection study. Knockdown of endogenous stathmin reduced sensitivity to apoptosis in replicon cells. Meanwhile, constitutively active stathmin increased sensitivity to apoptosis in replicon cells. In addition, overexpression of constitutively active stathmin reduced cell proliferation in both control and replicon cells. These findings implicate, for the first time, a novel role for stathmin in viral replication-related apoptosis. Stathmin's potential role in HCV replication and HCC make it a candidate for the future study of viral-induced malignancies.</p>","PeriodicalId":89169,"journal":{"name":"Journal of cell death","volume":"11 ","pages":"1179066018785141"},"PeriodicalIF":0.0,"publicationDate":"2018-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179066018785141","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36333626","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}
Journal of cell deathPub Date : 2018-01-03eCollection Date: 2018-01-01DOI: 10.1177/1179066017750902
Jessica Leigh Ritter, Caroline Attardo Genco
{"title":"<i>Neisseria gonorrhoeae</i>-Induced Inflammatory Pyroptosis in Human Macrophages is Dependent on Intracellular Gonococci and Lipooligosaccharide.","authors":"Jessica Leigh Ritter, Caroline Attardo Genco","doi":"10.1177/1179066017750902","DOIUrl":"https://doi.org/10.1177/1179066017750902","url":null,"abstract":"<p><p><i>Neisseria gonorrhoeae</i>, the human obligate pathogen responsible for the sexually transmitted disease gonorrhea, has evolved several mechanisms to evade the host immune response. One such mechanism is the modulation of host cell death pathways. In this study, we defined cell death pathways induced by <i>N gonorrhoeae</i> in human monocyte-derived macrophages (MDMs). In a dose-dependent manner, <i>N gonorrhoeae</i> stimulation of MDMs resulted in caspase 1 and 4-dependent cell deaths, indicative of canonical and noncanonical pyroptosis, respectively. Internalization of bacteria or stimulation with lipooligosaccharide (LOS) specifically induced pyroptosis in MDMs and increased secretion of IL-1β. Collectively, our results demonstrate that <i>N gonorrhoeae</i> induces inflammatory pyroptosis in human macrophages due in part to intracellular LOS. We propose that this in turn may exacerbate inflammatory outcomes observed during mucosal infection.</p>","PeriodicalId":89169,"journal":{"name":"Journal of cell death","volume":"11 ","pages":"1179066017750902"},"PeriodicalIF":0.0,"publicationDate":"2018-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179066017750902","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35823187","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}
Journal of cell deathPub Date : 2017-09-20eCollection Date: 2017-01-01DOI: 10.1177/1179066017731564
Mohammad Althubiti
{"title":"Spleen Tyrosine Kinase Inhibition Modulates p53 Activity.","authors":"Mohammad Althubiti","doi":"10.1177/1179066017731564","DOIUrl":"https://doi.org/10.1177/1179066017731564","url":null,"abstract":"<p><p>Spleen tyrosine kinase (SYK) is a cytoplasmic enzyme that promotes survival and proliferation of B cells. SYK inhibition has shown promising results in the treatment of arthritis and chronic lymphocytic leukemia (CLL). However, in other context, it has been shown that SYK overexpression in epithelial cancer cells induced senescence in p53-dependent mechanism, which underscored its antineoplastic activity in vitro. Here, we show that SYK was induced in response of DNA damage in parallel with p53 levels. In addition, using chemical inhibitors of SYK reduced p53 levels in HCT116 and HT1080 cell lines, which underlines the role of SYK inhibition on p53 activity. Furthermore, SYK inhibition modulated the cell growth, which resulted in a decreasing in cell death. Interestingly, SYK expression showed a positive prognosis in patients with solid tumors in correlations with their survival rates, as expected negative correlation was seen between SYK expression and survival rate of patients with CLL. In conclusion, these findings demonstrate that SYK inhibition modulates p53 expression and activity in HCT116 and HT1080 cells. Reconsidering using of SYK inhibitors in clinical setting in the future should be evaluated carefully in accordance with these findings to prevent the formation of secondary malignancies.</p>","PeriodicalId":89169,"journal":{"name":"Journal of cell death","volume":"10 ","pages":"1179066017731564"},"PeriodicalIF":0.0,"publicationDate":"2017-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179066017731564","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35663861","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}
Journal of cell deathPub Date : 2017-03-23eCollection Date: 2017-01-01DOI: 10.1177/1179670717694523
Stephen F Larner, Jonathan Wang, Jared Goodman, Megan B O'Donoghue Altman, Meiguo Xin, Kevin K W Wang
{"title":"In Vitro Neurotoxicity Resulting from Exposure of Cultured Neural Cells to Several Types of Nanoparticles.","authors":"Stephen F Larner, Jonathan Wang, Jared Goodman, Megan B O'Donoghue Altman, Meiguo Xin, Kevin K W Wang","doi":"10.1177/1179670717694523","DOIUrl":"https://doi.org/10.1177/1179670717694523","url":null,"abstract":"<p><p>Laboratory and industrial production of various nanoparticles, single-walled nanotubes (SWNTs), fullerene (C60), cadmium selenide (CdSe) quantum dots, carbon black (CB), and dye-doped silica nanospheres (NSs), has greatly increased in the past 15 years. However, little research has been done to analyze the toxicity of these materials. With recent studies showing that nano-substances can cross the blood-brain barrier, we examined the neurotoxicity of these manufactured nanoparticles. By employing the rat PC-12 neuronal-like cell line as the basis for our studies, we were able to evaluate the toxicity caused by these five nanoparticles. The level of toxicity was measured by testing for cell viability using the lactate dehydrogenase (LDH) cell viability assay, morphological analysis of changes in cellular structures, and Western blot analyses of αII-spectrin breakdown products (SBDP) as cell death indicators. Our results showed cytotoxicity in nondifferentiated PC-12 cells exposed to CB (10-100 μg/mL), SWNTs (10-100 μg/mL), C60 (100 μg/mL), CdSe (10 μg/mL), CB (500 μg/mL), and dye-doped silicon NSs (10 μg/mL). Exposure to higher concentrations (100 μg/mL) of SWNTs, CB, and C60 increased the formation of SBDP150/145, as well as cell membrane contraction and the formation of cytosolic vacuoles. The incorporations of the nanoparticles into cell cytoplasm were observed using the fluorescent dye-doped NSs in both nondifferentiated and nerve growth factor (NGF)-differentiated PC-12 cells. When PC-12 cells are differentiated, they appeared to be even more sensitive to cytotoxicity of nanoparticles such as CB 10 nm (10-100 μg/mL), CB 100 nm (10-100 μg/mL), and CdSe (1-10 μg/mL).</p>","PeriodicalId":89169,"journal":{"name":"Journal of cell death","volume":"10 ","pages":"1179670717694523"},"PeriodicalIF":0.0,"publicationDate":"2017-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179670717694523","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34966709","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}
Journal of cell deathPub Date : 2017-02-24eCollection Date: 2017-01-01DOI: 10.1177/1179670717691251
Benoite Méry, Jean-Baptiste Guy, Alexis Vallard, Sophie Espenel, Dominique Ardail, Claire Rodriguez-Lafrasse, Chloé Rancoule, Nicolas Magné
{"title":"In Vitro Cell Death Determination for Drug Discovery: A Landscape Review of Real Issues.","authors":"Benoite Méry, Jean-Baptiste Guy, Alexis Vallard, Sophie Espenel, Dominique Ardail, Claire Rodriguez-Lafrasse, Chloé Rancoule, Nicolas Magné","doi":"10.1177/1179670717691251","DOIUrl":"https://doi.org/10.1177/1179670717691251","url":null,"abstract":"Cell death plays a crucial role for a myriad of physiological processes, and several human diseases such as cancer are characterized by its deregulation. There are many methods available for both quantifying and qualifying the accurate process of cell death which occurs. Choosing the right assay tool is essential to generate meaningful data, provide sufficient information for clinical applications, and understand cell death processes. In vitro cell death assays are important steps in the search for new therapies against cancer as the ultimate goal remains the elaboration of drugs that interfere with specific cell death mechanisms. However, choosing a cell viability or cytotoxicity assay among the many available options is a daunting task. Indeed, cell death can be approached by several viewpoints and require a more holistic approach. This review provides an overview of cell death assays usually used in vitro for assessing cell death so as to elaborate new potential chemotherapeutics and discusses considerations for using each assay.","PeriodicalId":89169,"journal":{"name":"Journal of cell death","volume":"10 ","pages":"1179670717691251"},"PeriodicalIF":0.0,"publicationDate":"2017-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179670717691251","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34966708","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}
Journal of cell deathPub Date : 2017-02-20eCollection Date: 2017-01-01DOI: 10.1177/1179670716685085
Michael G Kemp
{"title":"Crosstalk Between Apoptosis and Autophagy: Environmental Genotoxins, Infection, and Innate Immunity.","authors":"Michael G Kemp","doi":"10.1177/1179670716685085","DOIUrl":"10.1177/1179670716685085","url":null,"abstract":"<p><p>Autoimmune disorders constitute a major and growing health concern. However, the genetic and environmental factors that contribute to or exacerbate disease symptoms remain unclear. Type I interferons (IFNs) are known to break immune tolerance and be elevated in the serum of patients with autoimmune diseases such as lupus. Extensive work over the past decade has characterized the role of a protein termed stimulator of interferon genes, or STING, in mediating IFN expression and activation in response to cytosolic DNA and cyclic dinucleotides. Interestingly, this STING-dependent innate immune pathway both utilizes and is targeted by the cell's autophagic machinery. Given that aberrant interplay between the apoptotic and autophagic machineries contributes to deregulation of the STING-dependent pathway, IFN-regulated autoimmune phenotypes may be influenced by the combined exposure to environmental carcinogens and pathogenic microorganisms and viruses. This review therefore summarizes recent data regarding these important issues in the field of autoimmunity.</p>","PeriodicalId":89169,"journal":{"name":"Journal of cell death","volume":"9 ","pages":"1179670716685085"},"PeriodicalIF":0.0,"publicationDate":"2017-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/de/79/10.1177_1179670716685085.PMC5392045.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34964664","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}