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Cell Death Discovery

Hui Zhao, Xuan Qin, Dan Yang, Yanhong Jiang, Weihao Zheng, Dongyuan Wang, Yuan Tian, Qisong Liu, Naihan Xu, Zigang Li
Cytolytic peptides are an emerging class of promising cancer therapeutics shown to overcome drug resistance. They eliminate cancer cells via disruption of the phospholipid bilayer of cell membranes, a mechanism that differentiates it from traditional treatments. However, applications of lytic peptides via systematic administration are hampered by nonspecific toxicity. Here, we describe activatable, masked lytic peptides that are conjugated with anionic peptides via a cleavable linker sensitive to matrix metalloproteinases (Ac-w-βA-e8-XPLG*LAG-klUklUkklUklUk-NH2; lower case letters in the sequences represent D-amino-acids, U=Aib, α-aminoisobutyric acid, *cleavage site)...
2017: Cell Death Discovery
Jian Wang, Chuyi Xu, Qiuyu Zheng, Kai Yang, Ning Lai, Tao Wang, Haiyang Tang, Wenju Lu
Previous studies have demonstrated that besides the classic canonical transient receptor potential channel family, Orai family and stromal interaction molecule 1 (STIM1) might also be involved in the regulation of store-operated calcium channels (SOCCs). An increase in cytosolic free Ca2+ concentration promoted by store-operated Ca2+ entry (SOCE) in pulmonary arterial smooth muscle cells (PASMCs) is a major trigger for pulmonary vasoconstriction and proliferation and migration of PASMCs. In this study, our data revealed the following: (1) in both rat distal pulmonary arteries and PASMCs, chronic hypoxia exposure upregulated the expression of Orai1 and Orai2, without affecting Orai3 and STIM1; (2) either heterozygous knockout of HIF-1α in mice or knockdown of HIF-1α in PASMCs abolished the hypoxic upregulation of Orai2, but not Orai1, suggesting the hypoxic upregulation of Orai2 depends on HIF-1α; and (3) using small interference RNA knockdown strategies, Orai1, 2, 3 and STIM1 were all shown to mediate SOCE in hypoxic PASMCs...
2017: Cell Death Discovery
Sunwang Xu, Ming Zhan, Jian Wang
Gallbladder cancer (GBC), with late diagnosis, rapid disease progression and early metastasis, is a highly aggressive malignant tumor found worldwide. Patients with GBC have poor survival, low curative resection rates and early recurrence. For such a lethal tumor, uncovering the mechanisms and exploring new strategies to prevent tumor progression and metastasis are critically important. Epithelial-to-mesenchymal transition (EMT) has a prominent role in the early steps of tumor progression and metastasis by initiating polarized epithelial cell transition into motile mesenchymal cells...
2017: Cell Death Discovery
Papri Nag, Pooja Rani Aggarwal, Sudip Ghosh, Kanika Narula, Rajul Tayal, Nidhi Maheshwari, Niranjan Chakraborty, Subhra Chakraborty
Although precisely controlled innate immune response is governed by conserved cellular events in phylogenetically diverse hosts, the underlying molecular mechanisms by which this process is regulated against a multi-host pathogen remain unknown. Fusarium oxysporum is a model multi-host pathogen, known to be associated with neuronal stress in humans and vascular wilt in plants. The interaction between innate immune and neuronal pathways is the basis of many diverse biological responses. How these processes are coordinated in response to fungal disease is not well understood...
2017: Cell Death Discovery
Matteo Cassandri, Artem Smirnov, Flavia Novelli, Consuelo Pitolli, Massimiliano Agostini, Michal Malewicz, Gerry Melino, Giuseppe Raschellà
Zinc-finger proteins (ZNFs) are one of the most abundant groups of proteins and have a wide range of molecular functions. Given the wide variety of zinc-finger domains, ZNFs are able to interact with DNA, RNA, PAR (poly-ADP-ribose) and other proteins. Thus, ZNFs are involved in the regulation of several cellular processes. In fact, ZNFs are implicated in transcriptional regulation, ubiquitin-mediated protein degradation, signal transduction, actin targeting, DNA repair, cell migration, and numerous other processes...
2017: Cell Death Discovery
Lucian DiPeso, Daisy X Ji, Russell E Vance, Jordan V Price
Although much insight has been gained into the mechanisms by which activation of the inflammasome can trigger pyroptosis in mammalian cells, the precise kinetics of the end stages of pyroptosis have not been well characterized. Using time-lapse fluorescent imaging to analyze the kinetics of pyroptosis in individual murine macrophages, we observed distinct stages of cell death and cell lysis. Our data demonstrate that cell membrane permeability resulting from gasdermin D pore formation is coincident with the cessation of cell movement, loss of mitochondrial activity, and cell swelling, events that can be uncoupled from cell lysis...
2017: Cell Death Discovery
Nidhi Srivastava, Asha Shelly, Manmohan Kumar, Archana Pant, Bhabatosh Das, Tanmay Majumdar, Shibnath Mazumder
Toll-like receptor 4 (TLR4) plays a critical role in host immunity against Gram-negative bacteria. It transduces signals through two distinct TIR-domain-containing adaptors, MyD88 and TRIF, which function at the plasma membrane and endosomes, respectively. Using zebrafish Aeromonas hydrophila infection model, we demonstrate that synchronization of MyD88 and TRIF dependent pathways is critical for determining the fate of infection. Zebrafish were infected with A. hydrophila, and bacterial recovery studies suggested its effective persistence inside the host...
2017: Cell Death Discovery
Masakazu Hamada, Hiroyasu Kameyama, Soichi Iwai, Yoshiaki Yura
Sphingosine kinase 1 (SphK1) overexpressed in head and neck squamous cell carcinoma (SCC) regulates tumor growth. The effects of PF-543, a specific SphK1 inhibitor, on human SCC cells were examined. The proportion of viable cells after PF-543 treatment decreased in a time- and dose-dependent manner, and cell death occurred in SphK1-expressing SCC cells. Flow cytometry analysis revealed that PF-543 induced both necrosis and apoptosis. PF-543 also induced granular accumulation of LC3 and conversion from LC3-I to LC3-II, which was blocked by autophagy inhibitors, wortmannin, 3-methyladenine (3-MA), and bafilomycin A1...
2017: Cell Death Discovery
Gianmaria Liccardi, Luca L Fava
No abstract text is available yet for this article.
2017: Cell Death Discovery
Amy C Flor, Don Wolfgeher, Ding Wu, Stephen J Kron
At their proliferative limit, normal cells arrest and undergo replicative senescence, displaying large cell size, flat morphology, and senescence-associated beta-galactosidase (SA-β-Gal) activity. Normal or tumor cells exposed to genotoxic stress undergo therapy-induced senescence (TIS), displaying a similar phenotype. Senescence is considered a DNA damage response, but cellular heterogeneity has frustrated identification of senescence-specific markers and targets. To explore the senescent cell proteome, we treated tumor cells with etoposide and enriched SA-β-Gal(HI) cells by fluorescence-activated cell sorting (FACS)...
2017: Cell Death Discovery
Mahmoud Toulany, Julia Maier, Mari Iida, Simone Rebholz, Marina Holler, Astrid Grottke, Manfred Jüker, Deric L Wheeler, Ulrich Rothbauer, H Peter Rodemann
Akt1 through the C-terminal domain interacts with the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and stimulates the repair of DNA double-strand breaks (DSBs) in K-RAS-mutated (K-RASmut) cells. We investigated the interactions of distinct domain(s) of DNA-PKcs in binding to full-length Akt1. Similarly, we analyzed potential interactions of DNA-PKcs with Akt2 and Akt3. Finally the effect of Akt isoforms in cell proliferation and tumor growth was tested. We demonstrated that Akt1 preferentially binds to the N-terminal domain of DNA-PKcs using pull-down studies with distinct eGFP-tagged DNA-PKcs fragments that were expressed by plasmids in combination with mCherry-tagged full-length Akt isoforms...
2017: Cell Death Discovery
Ruiwei Jiang, Lijun Ding, Jianjun Zhou, Chenyang Huang, Qun Zhang, Yue Jiang, Jingyu Liu, Qiang Yan, Xin Zhen, Jianxin Sun, Guijun Yan, Haixiang Sun
HOXA10 has emerged as an important molecular marker of endometrial receptivity. Recurrent implantation failure (RIF) after in vitro fertilization-embryo transplantation (IVF-ET) treatment is associated with impaired endometrial receptivity, but the exact underlying mechanism of this phenomenon remains elusive. Here we found that HOXA10 was modified by small ubiquitin like-modifier 1 (SUMO1) at the evolutionarily conserved lysine 164 residue. Sumoylation inhibited HOXA10 protein stability and transcriptional activity without affecting its subcellular localization...
2017: Cell Death Discovery
Han Han, Hui Zhou, Jing Li, Xiuyan Feng, Dan Zou, Weiqiang Zhou
To investigate the ability of SAHA-induced TRAIL DR5-CTSB crosstalk to initiate the breast cancer autophagy, RTCA assay was performed to assess the effect of SAHA on breast cancer cells, and western blot and ELISA were used to verify the inductive effects on expression of CTSB. Breast cancer cells were transfected with TRAIL DR5 siRNA to block the function of TRAIL DR5. Cell viability and apoptosis of breast cancer cells were analyzed using a muse cell analyzer. The distribution of LC3-II in TRAIL DR5-silenced breast cancer cells treated with SAHA was observed by immunofluorescence microscopy, the mRNA levels of autophagy-related genes were detected by RNA microarray, and the activity of autophagy-related signaling pathways was screened by MAPK antibody array...
2017: Cell Death Discovery
Vilma Dembitz, Hrvoje Lalic, Dora Visnjic
Pharmacological modulators of AMP-dependent kinase (AMPK) have been suggested in treatment of cancer. The biguanide metformin and 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) have been reported to inhibit proliferation of solid tumors and hematological malignancies, but their role in differentiation is less explored. Our previous study demonstrated that AICAR alone induced AMPK-independent expression of differentiation markers in monocytic U937 leukemia cells, and no such effects were observed in response to metformin...
2017: Cell Death Discovery
Yansong Xue, Min Du, Haiqing Sheng, Carolyn J Hovde, Mei-Jun Zhu
Autophagy is a pivotal innate immune response that not only degrades cytosolic components, but also serves as one of the critical antimicrobial mechanisms eliminating intracellular pathogens. However, its role in host defense against extracellular pathogens is largely unknown. Here we showed that E. coli O157:H7 altered autophagy to evade host defense and facilitate adhesion. Enhancing host cell autophagy with tumor necrosis factor (TNF), host starvation or rapamycin reduced the adherence of E. coli O157:H7 to HT-29 cells...
2017: Cell Death Discovery
Nina M Storey, David G Lambert
No abstract text is available yet for this article.
2017: Cell Death Discovery
Anju Singh, Sivakumar Periasamy, Meenakshi Malik, Chandra Shekhar Bakshi, Laurie Stephen, Jeffrey G Ault, Carmen A Mannella, Timothy J Sellati
Infection with Francisella tularensis ssp. tularensis (Ft) strain SchuS4 causes an often lethal disease known as tularemia in rodents, non-human primates, and humans. Ft subverts host cell death programs to facilitate their exponential replication within macrophages and other cell types during early respiratory infection (⩽72 h). The mechanism(s) by which cell death is triggered remains incompletely defined, as does the impact of Ft on mitochondria, the host cell's organellar 'canary in a coal mine'. Herein, we reveal that Ft infection of host cells, particularly macrophages and polymorphonuclear leukocytes, drives necroptosis via a receptor-interacting protein kinase 1/3-mediated mechanism...
2017: Cell Death Discovery
Rosamaria Lappano, Anna Sebastiani, Francesca Cirillo, Damiano Cosimo Rigiracciolo, Giulia Raffaella Galli, Rosita Curcio, Roberta Malaguarnera, Antonino Belfiore, Anna Rita Cappello, Marcello Maggiolini
The saturated medium-chain fatty-acid lauric acid (LA) has been associated to certain health-promoting benefits of coconut oil intake, including the improvement of the quality of life in breast cancer patients during chemotherapy. As it concerns the potential to hamper tumor growth, LA was shown to elicit inhibitory effects only in colon cancer cells. Here, we provide novel insights regarding the molecular mechanisms through which LA triggers antiproliferative and pro-apoptotic effects in both breast and endometrial cancer cells...
2017: Cell Death Discovery
Bhavana Chhunchha, Prerna Singh, W Daniel Stamer, Dhirendra P Singh
A progressive decline in antioxidant potential and accumulation of reactive oxygen species (ROS) are major causes of pathogenesis of several diseases, including glaucoma. Trabecular meshwork (TM) dysfunction resulting in higher intraocular pressure (IOP) is a hallmark of glaucoma, but its causes are unclear. Using human (h) TM cells derived from glaucomatous and normal subjects of different ages and cells facing oxidative-stress, we showed that specific loss of moonlighting antioxidant protein Peroxiredoxin (Prdx) 6 in aging or in glaucomatous TM cells caused ROS accumulation and pathobiological changes in TM cells...
2017: Cell Death Discovery
Xiaolan Zhu, Li Huang, Jie Gong, Chun Shi, Zhiming Wang, Bingkun Ye, Aiguo Xuan, Xiaosong He, Dahong Long, Xiao Zhu, Ningfang Ma, Shuilong Leng
Targeting endoplasmic reticulum (ER) stress is being investigated for its anticancer effect in various cancers, including cervical cancer. However, the molecular pathways whereby ER stress mediates cell death remain to be fully elucidated. In this study, we confirmed that ER stress triggered by compounds such as brefeldin A (BFA), tunicamycin (TM), and thapsigargin (TG) leads to the induction of the unfolded protein response (UPR) in cervical cancer cell lines, which is characterized by elevated levels of inositol-requiring kinase 1α, glucose-regulated protein-78, and C/EBP homologous protein, and swelling of the ER observed by transmission electron microscope (TEM)...
2017: Cell Death Discovery
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