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Cell Death Discovery

Tai-Yu Lai, I-Ju Chen, Ruey-Jen Lin, Guo-Shiou Liao, Hui-Ling Yeo, Ching-Liang Ho, Jen-Chine Wu, Nai-Chuan Chang, Andy Chi-Lung Lee, Alice L Yu
FUT1 and FUT2 encode alpha 1, 2-fucosyltransferases which catalyze the addition of alpha 1, 2-linked fucose to glycans. Glycan products of FUT1 and FUT2, such as Globo H and Lewis Y, are highly expressed on malignant tissues, including breast cancer. Herein, we investigated the roles of FUT1 and FUT2 in breast cancer. Silencing of FUT1 or FUT2 by shRNAs inhibited cell proliferation in vitro and tumorigenicity in mice. This was associated with diminished properties of cancer stem cell (CSC), including mammosphere formation and CSC marker both in vitro and in xenografts...
2019: Cell Death Discovery
Yanfei Li, Cuiping Wang, Tingting Li, Linlin Ma, Fangzhou Fan, Yueling Jin, Junwei Shen
As the most severe manifestation of coronary artery disease, myocardial infarction (MI) is a complex and multifactorial pathophysiologic process. However, the pathogenesis that underlies MI remains unclear. Here, we generated a MI mouse model by ligation of the proximal left anterior descending coronary artery. The transcriptome and proteome, at different time points after MI, were detected and analysed. Immune-related pathways, cell cycle-related pathways, and extracellular matrix remodelling-related pathways were significantly increased after MI...
2019: Cell Death Discovery
Cintia Carla da Hora, Kelsey Pinkham, Litia Carvalho, Max Zinter, Elie Tabet, Ichiro Nakano, Bakhos A Tannous, Christian E Badr
Glioblastoma is an incurable and highly aggressive brain tumor. Understanding therapeutic resistance and survival mechanisms driving this tumor type is key to finding effective therapies. Smac mimetics (SM) emerged as attractive cancer therapeutics particularly for tumor populations that are highly resistant to conventional apoptosis-inducing therapies. We evaluated the therapeutic efficacy of SM on Glioma stem-like cells (GSCs) and showed that this family of compounds stimulates an adaptive response triggered by TNFα...
2019: Cell Death Discovery
Benazir Siddeek, Claire Mauduit, Hassib Chehade, Guillaume Blin, Marjorie Liand, Mariapia Chindamo, Mohamed Benahmed, Umberto Simeoni
Heart failure is a worldwide leading cause of death. Diet and obesity are particularly of high concern in heart disease etiology. Gravely, altered nutrition during developmental windows of vulnerability can have long-term impact on heart health; however, the underlying mechanisms are poorly understood. In the understanding of the initiation of chronic diseases related to developmental exposure to environmental challenges, deregulations in epigenetic mechanisms including micro-RNAs have been proposed as key events...
2019: Cell Death Discovery
Xian-Jun Wang, Wang Chen, Xiao-Ting Fu, Jin-Kui Ma, Mei-Hong Wang, Ya-Jun Hou, Da-Chen Tian, Xiao-Yan Fu, Cun-Dong Fan
[This corrects the article DOI: 10.1038/s41420-018-0114-x.].
2019: Cell Death Discovery
Fabiana V Mello, Marcelo G P Land, Elaine S Costa, Cristina Teodósio, María-Luz Sanchez, Paloma Bárcena, Rodrigo T Peres, Carlos E Pedreira, Liliane R Alves, Alberto Orfao
Erythropoiesis has been extensively studied using in vitro and in vivo animal models. Despite this, there is still limited data about the gene expression profiles (GEP) of primary (ex vivo) normal human bone marrow (BM) erythroid maturation. We investigated the GEP of nucleated red blood cell (NRBC) precursors during normal human BM erythropoiesis. Three maturation-associated populations of NRBC were identified and purified from (fresh) normal human BM by flow cytometry and the GEP of each purified cell population directly analyzed using DNA-oligonucleotide microarrays...
2019: Cell Death Discovery
Diane M Pereira, Sofia E Gomes, Pedro M Borralho, Cecília M P Rodrigues
Colon cancer has been proposed to be sustained by a small subpopulation of stem-like cells with unique properties allowing them to survive conventional therapies and drive tumor recurrence. Identification of targetable signaling pathways contributing to malignant stem-like cell maintenance may therefore translate into new therapeutic strategies to overcome drug resistance. Here we demonstrated that MEK5/ERK5 signaling activation is associated with stem-like malignant phenotypes. Conversely, using a panel of cell line-derived three-dimensional models, we showed that ERK5 inhibition markedly suppresses the molecular and functional features of colon cancer stem-like cells...
2019: Cell Death Discovery
Konstantin Bagnjuk, Jan Bernd Stöckl, Thomas Fröhlich, Georg Josef Arnold, Rüdiger Behr, Ulrike Berg, Dieter Berg, Lars Kunz, Cecily Bishop, Jing Xu, Artur Mayerhofer
The corpus luteum (CL) is a transient endocrine organ, yet molecular mechanisms resulting in its demise are not well known. The presence of phosphorylated mixed lineage kinase domain-like pseudokinase pMLKL(T357/S358) in human and nonhuman primate CL samples ( Macaca mulatta and Callithrix jacchus ) implied that necroptosis of luteal cells may be involved. In M. mulatta CL, pMLKL positive staining became detectable only from the mid-late luteal phase onwards, pointing to necroptosis during regression of the CL...
2019: Cell Death Discovery
Alessio Bocedi, Gianluca Ingrosso, Giada Cattani, Roberto Miceli, Elisabetta Ponti, Andrea Lancia, Sara Baldelli, Arianna Guidi, Maria Rosa Ciriolo, Maurizio Mattei, Giorgio Ricci
By looking at many studies describing the impact of ionizing irradiations in living mice on a few key detoxifying enzymes like catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase and glutathione transferase, we noted conflicting evidences: almost all papers finalized to demonstrate the protective effects of natural or synthetic drugs against the damage by irradiations, described also a relevant inactivation of these enzymes in the absence of these compounds. Conversely, no inactivation and even enhanced activity has been noted under similar irradiation modality in all studies supporting the "adaptive response"...
2019: Cell Death Discovery
Katharina Klöditz, Bengt Fadeel
Macrophage clearance of apoptotic cells has been extensively investigated, but less is known regarding the clearance of cells dying by other forms of programmed cell death, e.g., necroptosis or ferroptosis. Here, we established a model of three different cell deaths using the same cell line and the occurrence of distinct cell death modalities was verified by using the specific inhibitors, zVAD-fmk, necrostatin-1, and ferrostatin-1, respectively. Cell death was characterized by using transmission electron microscopy (TEM), the gold standard for the demarcation of different cell death modalities...
2019: Cell Death Discovery
Ezgi Kaya-Aksoy, Ahmet Cingoz, Filiz Senbabaoglu, Fidan Seker, Ilknur Sur-Erdem, Alisan Kayabolen, Tolga Lokumcu, Gizem Nur Sahin, Sercin Karahuseyinoglu, Tugba Bagci-Onder
Harakiri (HRK) is a BH3-only protein of the Bcl-2 family and regulates apoptosis by interfering with anti-apoptotic Bcl-2 and Bcl-xL proteins. While its function is mainly characterized in the nervous system, its role in tumors is ill-defined with few studies demonstrating HRK silencing in tumors. In this study, we investigated the role of HRK in the most aggressive primary brain tumor, glioblastoma multiforme (GBM). We showed that HRK is differentially expressed among established GBM cell lines and that HRK overexpression can induce apoptosis in GBM cells at different levels...
2019: Cell Death Discovery
Ayobami Matthew Olajuyin, Xiaoju Zhang, Hong-Long Ji
Alveolar type 2 progenitor cells (AT2) seem closest to clinical translation, specifying the evidence that AT2 may satisfactorily control the immune response to decrease lung injury by stabilizing host immune-competence and a classic and crucial resource for lung regeneration and repair. AT2 establish potential in benefiting injured lungs. However, significant discrepancies linger in our understanding vis-à-vis the mechanisms for AT2 as a regime for stem cell therapy as well as essential guiding information for clinical trials, including effectiveness in appropriate pre-clinical models, safety, mostly specifications for divergent lung injury patients...
2019: Cell Death Discovery
Xuanan Li, Shamima Islam, Min Xiong, Ndona N Nsumu, Mark W Lee, Li Qin Zhang, Yasuyoshi Ueki, Daniel P Heruth, Guanghua Lei, Shui Qing Ye
Nicotinamide phosphoribosyltransferase (NAMPT) functions in NAD synthesis, apoptosis, and inflammation. Dysregulation of NAMPT has been associated with several inflammatory diseases, including rheumatoid arthritis (RA). The purpose of this study was to investigate NAMPT's role in arthritis using mouse and cellular models. Collagen-induced arthritis (CIA) in DBA/1J Nampt +/- mice was evaluated by ELISA, micro-CT, and RNA-sequencing (RNA-seq). In vitro Nampt loss-of-function and gain-of-function studies on osteoclastogenesis were examined by TRAP staining, nascent RNA capture, luciferase reporter assays, and ChIP-PCR...
2019: Cell Death Discovery
Irina I Suvorova, Aleksandra R Knyazeva, Alexey V Petukhov, Nicolay D Aksenov, Valery A Pospelov
Resveratrol, a natural polyphenolic compound, shows many beneficial effects in various animal models. It increases efficiency of somatic cell reprograming into iPSCs and contributes to cell differentiation. Here, we studied the effect of resveratrol on proliferation and pluripotency of mouse embryonic stem cells (mESCs). Our results demonstrate that resveratrol induces autophagy in mESCs that is provided by the activation of the AMPK/Ulk1 pathway and the concomitant suppression of the activity of the mTORC1 signaling cascade...
2019: Cell Death Discovery
Jenna Susan Bleloch, André du Toit, Liezl Gibhard, Serah Kimani, Reyna Deeya Ballim, Minkyu Lee, Angelique Blanckenberg, Selwyn Mapolie, Lubbe Wiesner, Ben Loos, Sharon Prince
Rhabdomyosarcoma (RMS) forms in skeletal muscle and is the most common soft tissue sarcoma in children and adolescents. Current treatment is associated with debilitating side effects and treatment outcomes for patients with metastatic disease are dismal. Recently, a novel binuclear palladacycle, AJ-5, was shown to exert potent cytotoxicity in melanoma and breast cancer and to present with negligible adverse effects in mice. This study investigates the anti-cancer activity of AJ-5 in alveolar and embryonal RMS...
2019: Cell Death Discovery
Yen-Wen Liu, Yi-Hsein Fang, Chi-Ting Su, Shiaw-Min Hwang, Ping-Yen Liu, Sheng-Nan Wu
Owing to the beneficial properties of amniotic fluid-derived stem cells (AFSCs), including pluripotency and the lack of ethical issues associated with embryonic stem cells (ESCs), they should be a promising cell source for regenerative medicine. However, how to differentiate AFSCs into contracting cardiomyocytes has not been established. In this study, a well-established, direct cardiac differentiation protocol involving the modulation of Wnt signaling was used to differentiate Oct 3/4+ AFSCs into cardiomyocytes...
2019: Cell Death Discovery
Chenbo Zeng, Chi-Chang Weng, Mark E Schneider, Laura Puentes, Aladdin Riad, Kuiying Xu, Mehran Makvandi, Linda Jin, William G Hawkins, Robert H Mach
Sigma-2 receptors have been implicated in both tumor proliferation and neurodegenerative diseases. Recently the sigma-2 receptor was identified as transmembrane protein 97 (TMEM97). Progesterone receptor membrane component 1 (PGRMC1) was also recently reported to form a complex with TMEM97 and the low density lipoprotein (LDL) receptor, and this trimeric complex is responsible for the rapid internalization of LDL. Sigma-2 receptor ligands with various structures have been shown to induce cell death in cancer cells...
2019: Cell Death Discovery
Giovanna Priante, Monica Ceol, Lisa Gianesello, Claudio Furlan, Dorella Del Prete, Franca Anglani
Nephrocalcinosis is a clinicopathological entity characterized by microscopic calcium crystals in the renal parenchyma, within the tubular lumen or in the interstitium. Crystal binding to tubular cells may be the cause underlying nephrocalcinosis and nephrolithiasis. Pathological circumstances, such as acute cortical necrosis, may induce healthy cells to acquire a crystal-binding phenotype. The present study aimed to investigate whether human renal proximal tubular cells (HK-2 cells) can form calcium phosphate deposits under osteogenic conditions, and whether apoptosis and/or osteogenic-like processes are involved in cell calcification...
2019: Cell Death Discovery
Katelyn G Ponder, Lawrence H Boise
Caspase-3 is a cysteine-aspartic acid protease that cleaves cellular targets and executes cell death. Our current understanding is caspase-3 is activated by the cleavage of the interdomain linker and then subsequent cleavage of the N-terminal prodomain. However, previous reports have suggested that removal of the prodomain can result in the constitutive activation of caspase-3, although other studies have not observed this. To address this question in a more physiological setting, we developed an inducible doxycycline system to express a mutant form of caspase-3 that lacks the prodomain (∆28)...
2019: Cell Death Discovery
Jun-Wen Shi, Ting-Ting Zhang, Wei Liu, Jie Yang, Xiao-Lin Lin, Jun-Shuang Jia, Hong-Fen Shen, Sheng-Chun Wang, Jing Li, Wen-Tao Zhao, Wei-Wang Gu, Yan Sun, Dong Xiao
Unexpectedly, we found that c-Myc-expressing porcine embryonic fibroblasts (PEFs) subcutaneously implanted into nude mice formed cartilage-like tissues in vivo, while previous studies revealed the direct conversion of mouse and human somatic cells into chondrocytes by the combined use of several defined factors, including c-Myc, which prompted us to explore whether PEFs can be reprogrammed to become pig induced chondrocyte-like cells (piCLCs) via ectopic expression of c-Myc alone. In this study, c-Myc-expressing PEFs, designated piCLCs, which exhibited a significantly enhanced proliferation ability in vitro, displayed a chondrogenic phenotypes in vitro, as shown by the cell morphology, toluidine blue staining, alcian blue staining and chondrocyte marker gene expression...
2019: Cell Death Discovery
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