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Cell Death & Disease

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https://www.readbyqxmd.com/read/28230866/oridonin-induces-autophagy-via-inhibition-of-glucose-metabolism-in-p53-mutated-colorectal-cancer-cells
#1
Zhuo Yao, Fuhua Xie, Min Li, Zirui Liang, Wenli Xu, Jianhua Yang, Chang Liu, Hongwangwang Li, Hui Zhou, Liang-Hu Qu
The Warburg effect is an important characteristic of tumor cells, making it an attractive therapeutic target. Current anticancer drug development strategies predominantly focus on inhibitors of the specific molecular effectors involved in tumor cell proliferation. These drugs or natural compounds, many of which target the Warburg effect and the underlying mechanisms, still need to be characterized. To elucidate the anticancer effects of a natural diterpenoid, oridonin, we first demonstrated the anticancer activity of oridonin both in vitro and in vivo in colorectal cancer (CRC) cells...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28230865/erbb4-signaling-stimulates-pro-inflammatory-macrophage-apoptosis-and-limits-colonic-inflammation
#2
Michael A Schumacher, Matija Hedl, Clara Abraham, Jessica K Bernard, Patricia R Lozano, Jonathan J Hsieh, Dana Almohazey, Edie B Bucar, Shivesh Punit, Peter J Dempsey, Mark R Frey
Efficient clearance of pro-inflammatory macrophages from tissues after resolution of a challenge is critical to prevent prolonged inflammation. Defects in clearance can contribute to conditions such as inflammatory bowel disease, and thus may be therapeutically targetable. However, the signaling pathways that induce termination of pro-inflammatory macrophages are incompletely defined. We tested whether the ErbB4 receptor tyrosine kinase, previously not known to have role in macrophage biology, is involved in this process...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28230864/dicer-promotes-tumorigenesis-by-translocating-to-nucleus-to-promote-sfrp1-promoter-methylation-in-cholangiocarcinoma-cells
#3
Wenlong Cheng, Yongqiang Qi, Li Tian, Bing Wang, Wenhua Huang, Yongjun Chen
Dicer, a member of the RNase III family of endoribonucleases, has an important role in regulating methylation of CpG islands in mammal cancer cells. However, the underlying mechanism of action remains unclear. In this study, we demonstrated that upregulation of Dicer in cholangiocarcinoma (CCA) cells and its translocation to nuclues to interact with heterochromatin protein 1α (HP1α). The nuclear Dicer/HP1α complex appeared to promote both H3K9 trimethylation and DNA methylation of the secreted frizzled-related protein 1 (SFRP1) promoter...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28230863/oncogenic-role-of-rab-escort-protein-1-through-egfr-and-stat3-pathway
#4
Un-Jung Yun, Jee Young Sung, Seog-Yun Park, Sang-Kyu Ye, Jaegal Shim, Jae-Seon Lee, Masahiko Hibi, Young-Ki Bae, Yong-Nyun Kim
Rab escort protein-1 (REP1) is linked to choroideremia (CHM), an X-linked degenerative disorder caused by mutations of the gene encoding REP1 (CHM). REP1 mutant zebrafish showed excessive cell death throughout the body, including the eyes, indicating that REP1 is critical for cell survival, a hallmark of cancer. In the present study, we found that REP1 is overexpressed in human tumor tissues from cervical, lung, and colorectal cancer patients, whereas it is expressed at relatively low levels in the normal tissue counterparts...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28230862/inactivation-of-lsd1-triggers-senescence-in-trophoblast-stem-cells-by-induction-of-sirt4
#5
Josefina Castex, Dominica Willmann, Toufike Kanouni, Laura Arrigoni, Yan Li, Marcel Friedrich, Michael Schleicher, Simon Wöhrle, Mark Pearson, Norbert Kraut, Michaël Méret, Thomas Manke, Eric Metzger, Roland Schüle, Thomas Günther
Coordination of energy metabolism is essential for homeostasis of stem cells, whereas an imbalance in energy homeostasis causes disease and accelerated aging. Here we show that deletion or enzymatic inactivation of lysine-specific demethylase 1 (Lsd1) triggers senescence in trophoblast stem cells (TSCs). Genome-wide transcriptional profiling of TSCs following Lsd1 inhibition shows gene set enrichment of aging and metabolic pathways. Consistently, global metabolomic and phenotypic analyses disclose an unbalanced redox status, decreased glutamine anaplerosis and mitochondrial function...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28230861/ripk3-interactions-with-mlkl-and-camkii-mediate-oligodendrocytes-death-in-the-developing-brain
#6
Yi Qu, Jun Tang, Huiqing Wang, Shiping Li, Fengyan Zhao, Li Zhang, Q Richard Lu, Dezhi Mu
Oligodendrocyte progenitor cells (OPCs) death is a key contributor to cerebral white matter injury (WMI) in the developing brain. A previous study by our group indicated that receptor-interacting proteins (RIPs) are crucial in mediating necroptosis in developing neurons. However, whether this mechanism is involved in OPCs death is unclear. We aimed to explore the mechanisms of RIP-mediated oligodendrocytes (OLs) death in the developing brain. Oligodendrocytes necroptosis was induced by oxygen-glucose deprivation plus caspase inhibitor zVAD treatment (OGD/zVAD) in vitro...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28230860/carma2sh-and-ulk2-control-pathogen-associated-molecular-patterns-recognition-in-human-keratinocytes-psoriasis-linked-carma2sh-mutants-escape-ulk2-censorship
#7
Ivan Scudiero, Pellegrino Mazzone, Luca E D'Andrea, Angela Ferravante, Tiziana Zotti, Gianluca Telesio, Gabriele De Rubis, Carla Reale, Maddalena Pizzulo, Shanmugakonar Muralitharan, Pasquale Vito, Romania Stilo
The molecular complexes formed by specific members of the family of CARMA proteins, the CARD domain-containing adapter molecule BCL10 and MALT1 (CBM complex) represent a central hub in regulating activation of the pleiotropic transcription factor NF-κB. Recently, missense mutations in CARMA2sh have been shown to cause psoriasis in a dominant manner and with high penetrancy. Here, we demonstrate that in human keratinocytes CARMA2sh plays an essential role in the signal transduction pathway that connects pathogen-associated molecular patterns recognition to NF-κB activation...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28230859/a-novel-proinflammatory-role-for-granzyme-a
#8
Jacqueline A van Eck, Liling Shan, Jan Meeldijk, C Erik Hack, Niels Bovenschen
No abstract text is available yet for this article.
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28230858/ngs-based-transcriptome-profiling-reveals-biomarkers-for-companion-diagnostics-of-the-tgf-%C3%AE-receptor-blocker-galunisertib-in-hcc
#9
Yuan Cao, Rahul Agarwal, Francesco Dituri, Luigi Lupo, Paolo Trerotoli, Serena Mancarella, Peter Winter, Gianluigi Giannelli
Transforming growth factor-beta (TGF-β) signaling has gained extensive interest in hepatocellular carcinoma (HCC). The small molecule kinase inhibitor galunisertib, targeting the TGF-β receptor I (TGF-βRI), blocks HCC progression in preclinical models and shows promising effects in ongoing clinical trials. As the drug is not similarly effective in all patients, this study was aimed at identifying new companion diagnostics biomarkers for patient stratification. Next-generation sequencing-based massive analysis of cDNA ends was used to investigate the transcriptome of an invasive HCC cell line responses to TGF-β1 and galunisertib...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28230857/protein-phosphatase-4-coordinates-glial-membrane-recruitment-and-phagocytic-clearance-of-degenerating-axons-in-drosophila
#10
Lilly M Winfree, Sean D Speese, Mary A Logan
Neuronal damage induced by injury, stroke, or neurodegenerative disease elicits swift immune responses from glial cells, including altered gene expression, directed migration to injury sites, and glial clearance of damaged neurons through phagocytic engulfment. Collectively, these responses hinder further cellular damage, but the mechanisms that underlie these important protective glial reactions are still unclear. Here, we show that the evolutionarily conserved trimeric protein phosphatase 4 (PP4) serine/threonine phosphatase complex is a novel set of factors required for proper glial responses to nerve injury in the adult Drosophila brain...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28230856/ginsenoside-rg5-increases-cardiomyocyte-resistance-to-ischemic-injury-through-regulation-of-mitochondrial-hexokinase-ii-and-dynamin-related-protein-1
#11
Yi-Lin Yang, Jia Li, Kang Liu, Lei Zhang, Qun Liu, Baolin Liu, Lian-Wen Qi
Hexokinase-II (HK-II) and dynamin-related protein 1 (Drp1) regulate mitochondrial function differently. This study was designed to investigate the cardioprotective effect of ginsenoside Rg5 (Rg5) with emphasis on the regulation of mitochondrial HK-II and Drp1. Saturated acid palmitate (PA) stimulation increased lactate accumulation and induced cellular acidification by impairing the activity of pyruvate dehydrogenase (PDH) in cardiomyocytes, leading to HK-II dissociation from mitochondria. Rg5 improved PDH activity and prevented cellular acidification by combating fatty-acid oxidation, contributing to protecting mitochondrial HK-II...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28230855/simvastatin-induced-cell-cycle-arrest-through-inhibition-of-stat3-skp2-axis-and-activation-of-ampk-to-promote-p27-and-p21-accumulation-in-hepatocellular-carcinoma-cells
#12
Sin-Ting Wang, Hsiu J Ho, Jaw-Town Lin, Jeng-Jer Shieh, Chun-Ying Wu
Hepatocellular carcinoma (HCC) is characterized by a poor prognosis and is one of the leading causes of cancer-related death worldwide. Simvastatin, an HMG-CoA reductase inhibitor, which decreases cholesterol synthesis by inhibiting mevalonate pathways and is widely used to treat cardiovascular diseases. Simvastatin exhibits anticancer effects against several malignancies. However, the molecular mechanisms underlying the anticancer effects of simvastatin on HCC are still not well understood. In this study, we demonstrated simvastatin-induced G0/G1 arrest by inducing p21 and p27 accumulation in HepG2 and Hep3B cells...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28230854/opposite-effects-of-hdac5-and-p300-on-mrtf-a-related-neuronal-apoptosis-during-ischemia-reperfusion-injury-in-rats
#13
Na Li, Qiong Yuan, Xiao-Lu Cao, Ying Zhang, Zhen-Li Min, Shi-Qiang Xu, Zhi-Jun Yu, Jing Cheng, Chunxiang Zhang, Xia-Min Hu
Our recent study has revealed that the myocardin-related transcription factor-A (MRTF-A) is involved in the apoptosis of cortical neurons induced by ischemia/reperfusion (I/R). Histone deacetylase 5 (HDAC5) and histone acetyltransferase p300 (P300) are two well-known regulators for transcription factors; however, their roles in MRTF-A-related effect on neuronal injuries during I/R are still unclear. In this study, in a model rat cerebral I/R injury via middle cerebral artery occlusion and reperfusion, we found that the expression and activity of HDAC5 was upregulated, whereas p300 and MRTF-A were downregulated both in expression and activity during I/R...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28230853/mesenchymal-stromal-cells-inhibit-cd25-expression-via-the-mtor-pathway-to-potentiate-t-cell-suppression
#14
Hyun Seung Yoo, Kyuheon Lee, Kwangmin Na, Yong Xu Zhang, Hyun-Ja Lim, TacGhee Yi, Sun U Song, Myung-Shin Jeon
Mesenchymal stromal cells (MSCs) are known to suppress T-cell activation and proliferation. Several studies have reported that MSCs suppress CD25 expression in T cells. However, the molecular mechanism underlying MSC-mediated suppression of CD25 expression has not been fully examined. Here, we investigated the mTOR pathway, which is involved in CD25 expression in T cells. We showed that MSCs inhibited CD25 expression, which was restored in the presence of an inducible nitric oxide synthase (iNOS) inhibitor...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28206988/inhibition-of-autophagy-blocks-cathepsins-tbid-mitochondrial-apoptotic-signaling-pathway-via-stabilization-of-lysosomal-membrane-in-ischemic-astrocytes
#15
Xian-Yong Zhou, Yu Luo, Yong-Ming Zhu, Zhi-He Liu, Thomas A Kent, Jia-Guo Rong, Wei Li, Shi-Gang Qiao, Min Li, Yong Ni, Kazumi Ishidoh, Hui-Ling Zhang
Our previous study and others have demonstrated that autophagy is activated in ischemic astrocytes and contributes to astrocytic cell death. However, the mechanisms of ischemia-induced autophagy remain largely unknown. In this study, we established a rat's model of permanent middle cerebral artery occlusion (pMCAO) and an in vitro oxygen and glucose deprivation (OGD) model. Autophagy was inhibited by either pharmacological treatment with 3-methyladenine (3-MA) and wortmannin (Wort) or genetic treatment with knockdown of Atg5 in primary cultured astrocytes and knockout of Atg5 in mouse embryonic fibroblast (MEF) cells, respectively...
February 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28206987/id2-promotes-survival-of-glioblastoma-cells-during-metabolic-stress-by-regulating-mitochondrial-function
#16
Zhonghua Zhang, Gilbert J Rahme, Pranam D Chatterjee, Matthew C Havrda, Mark A Israel
Tumor cells proliferate in cellular environments characterized by a lack of optimal tissue organization resulting oftentimes in compromised cellular metabolism affecting nutrition, respiration, and energetics. The response of tumor cells to adverse environmental conditions is a key feature affecting their pathogenicity. We found that inhibitor of DNA binding 2 (ID2) expression levels significantly correlate with the ability of glioblastoma (GBM)-derived cell lines to survive glucose deprivation. ID2 suppressed mitochondrial oxidative respiration and mitochondrial ATP production by regulating the function of mitochondrial electron transport chain (mETC) complexes, resulting in reduced superoxide and reactive oxygen species (ROS) production from mitochondria...
February 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28206986/in-situ-generated-d-peptidic-nanofibrils-as-multifaceted-apoptotic-inducers-to-target-cancer-cells
#17
Xuewen Du, Jie Zhou, Huainin Wang, Junfeng Shi, Yi Kuang, Wu Zeng, Zhimou Yang, Bing Xu
Nanofibrils of small molecules, as a new class of biofunctional entities, exhibit emergent properties for controlling cell fates, but the relevant mechanism remains to be elucidated and the in vivo effect has yet to be examined. Here, we show that D-peptide nanofibrils, generated by enzyme-instructed self-assembly (EISA), pleiotropically activate extrinsic death signaling for selectively killing cancer cells. Catalyzed by alkaline phosphatases and formed in situ on cancer cells, D-peptide nanofibrils present autocrine proapoptotic ligands to their cognate receptors in a juxtacrine manner, as well as directly cluster the death receptors...
February 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28182016/arginylation-a-new-regulator-of-mrna-stability-and-heat-stress-response
#18
Kamalakshi Deka, Sougata Saha
No abstract text is available yet for this article.
February 9, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28182015/mcm7-promotes-cancer-progression-through-cyclin-d1-dependent-signaling-and-serves-as-a-prognostic-marker-for-patients-with-hepatocellular-carcinoma
#19
Kai Qu, Zhixin Wang, Haining Fan, Juan Li, Jie Liu, Pingping Li, Zheyong Liang, Hongli An, Yina Jiang, Qiushi Lin, Xiaoqun Dong, Peijun Liu, Chang Liu
DNA replication is a central procedure of cell proliferation, whereas aberrant DNA replication is indicated to be a driving force of oncogenesis. Minichromosome maintenance complex component 7 (MCM7) plays an essential role in initiating DNA replication. To investigate the potential oncogenic properties and prognostic value of MCM7 in hepatocellular carcinoma (HCC), we conducted immunohistochemistry staining of MCM7 in 153 HCC samples and found that MCM7 high expression level was associated with worse overall survival (OS) of HCC patients...
February 9, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28182014/starvation-at-birth-impairs-germ-cell-cyst-breakdown-and-increases-autophagy-and-apoptosis-in-mouse-oocytes
#20
Yong-Yong Wang, Yuan-Chao Sun, Xiao-Feng Sun, Shun-Feng Cheng, Bo Li, Xi-Feng Zhang, Massimo De Felici, Wei Shen
The female reproductive lifespan is largely determined by the size of primordial follicle pool, which is established following germ cell cyst breakdown around birth. Almost two-third of oocytes are lost during germ cell cysts breakdown, following autophagic and apoptosis mechanisms. To investigate a possible relationship between germ cell cyst breakdown and nutrition supply, we established a starvation model in mouse pups at birth and evaluated the dynamics of cyst breakdown during nutrient deprivation. Our results showed that after 36 h of starvation between 1...
February 9, 2017: Cell Death & Disease
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