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https://www.readbyqxmd.com/read/28213497/mitochondrial-damage-elicits-a-tcdd-inducible-poly-adp-ribose-polymerase-mediated-antiviral-response
#1
Tatsuya Kozaki, Jun Komano, Daiki Kanbayashi, Michihiro Takahama, Takuma Misawa, Takashi Satoh, Osamu Takeuchi, Taro Kawai, Shigeomi Shimizu, Yoshiharu Matsuura, Shizuo Akira, Tatsuya Saitoh
The innate immune system senses RNA viruses by pattern recognition receptors (PRRs) and protects the host from virus infection. PRRs mediate the production of immune modulatory factors and direct the elimination of RNA viruses. Here, we show a unique PRR that mediates antiviral response. Tetrachlorodibenzo-p-dioxin (TCDD)-inducible poly(ADP ribose) polymerase (TIPARP), a Cysteine3 Histidine (CCCH)-type zinc finger-containing protein, binds to Sindbis virus (SINV) RNA via its zinc finger domain and recruits an exosome to induce viral RNA degradation...
February 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28211974/whole-exome-sequencing-identified-1-base-pair-novel-deletion-in-bcl2-associated-athanogene-3-bag3-gene-associated-with-severe-dilated-cardiomyopathy-dcm-requiring-heart-transplant-in-multiple-family-members
#2
Muhammad Arshad Rafiq, Ayeshah Chaudhry, Melanie Care, Danna A Spears, Chantal F Morel, Robert M Hamilton
Dilated cardiomyopathy (DCM) is characterized by dilation and impaired contraction of the left ventricle or both ventricles. Among hereditary DCM, the genetic causes are heterogeneous, and include mutations encoding cytoskeletal, nucleoskeletal, mitochondrial, and calcium-handling proteins. We report three severely affected males, in a four-generation pedigree, with DCM phenotype who underwent cardiac transplant. Cardiomegaly with marked biventricular dilation and fibrosis were noticeable histopathological findings...
March 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28182330/heat-shock-protein-27-hsp27-hspb1-is-synthetic-lethal-to-cells-with-oncogenic-activation-of-met-egfr-and-braf
#3
John David Konda, Martina Olivero, Daniele Musiani, Simona Lamba, Maria Flavia Di Renzo
The small Heat Shock Protein of 27 KDa (HSP27) is highly expressed in many cancers and is associated with aggressive tumor behaviour, metastasis, poor prognosis and resistance to chemotherapy. We aimed at assessing the role of HSP27 in modulating responses to target therapies. We selected several oncogene-addicted cancer cell lines, which undergo either cell cycle blockade or cell death in response to agents that target the specific oncogene. Surprisingly, HSP27 suppression alone resulted in the apoptotic death of MET-addicted EBC-1 lung cancer cells, EGFR-addicted colorectal carcinoma DiFi cells and BRAF-addicted colorectal carcinoma COLO205 and OXCO-1 and melanoma COLO741 cells, all of which also undergo death when treated with the specific targeted agent...
February 9, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28181540/hiv-related-proteins-prolong-macrophage-survival-through-induction-of-triggering-receptor-expressed-on-myeloid-cells-1
#4
Zhihong Yuan, Xian Fan, Bashar Staitieh, Chetna Bedi, Paul Spearman, David M Guidot, Ruxana T Sadikot
Triggering receptor expressed on myeloid cells-1(TREM-1) is a member of the superimmunoglobulin receptor family. We have previously shown that TREM-1 prolongs survival of macrophages treated with lipoolysaccharide through Egr2-Bcl2 signaling. Recent studies suggest a role for TREM-1 in viral immunity. Human immunodeficiency virus-1 (HIV) targets the monocyte/macrophage lineage at varying stages of infection. Emerging data suggest that macrophages are key reservoirs for latent HIV even in individuals on antiretroviral therapy...
February 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28164169/adeno-associated-virus-serotype-9-driven-expression-of-bag3-improves-left-ventricular-function-in-murine-hearts-with-left-ventricular-dysfunction-secondary-to-a-myocardial-infarction
#5
Tijana Knezevic, Valerie D Myers, Feifei Su, JuFang Wang, Jianliang Song, Xue-Qian Zhang, Erhe Gao, Guofeng Gao, Madesh Muniswamy, Manish K Gupta, Jennifer Gordon, Kristen N Weiner, Joseph Rabinowitz, Frederick V Ramsey, Douglas G Tilley, Kamel Khalili, Joseph Y Cheung, Arthur M Feldman
OBJECTIVES: The present study was undertaken to test the hypothesis that gene delivery of BCL2-Associated Athanogene 3 (BAG3) to the heart of mice with left ventricular dysfunction secondary to a myocardial infarction could enhance cardiac performance. BACKGROUND: BAG3 is a 575 amino acid protein that has pleotropic functions in the cell including pro-autophagy and anti-apoptosis. Mutations in BAG3 have been associated with both skeletal muscle dysfunction and familial dilated cardiomyopathy and BAG3 levels are diminished in non-familial heart failure...
December 2016: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/28144784/bag3-is-involved-in-neuronal-differentiation-and-migration
#6
Antonietta Santoro, Vanessa Nicolin, Fulvio Florenzano, Alessandra Rosati, Mario Capunzo, Stefania L Nori
Bcl2-associated athanogene 3 (BAG3) protein belongs to the family of co-chaperones interacting with several heat shock proteins. It plays a key role in protein quality control and mediates the clearance of misfolded proteins. Little is known about the expression and cellular localization of BAG3 during nervous system development and differentiation. Therefore, we analyze the subcellular distribution and expression of BAG3 in nerve-growth-factor-induced neurite outgrowth in PC12 cells and in developing and adult cortex of mouse brain...
February 1, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28134252/thz1-targeting-cdk7-suppresses-stat-transcriptional-activity-and-sensitizes-t-cell-lymphomas-to-bcl2-inhibitors
#7
Florencia Cayrol, Pannee Praditsuktavorn, Tharu M Fernando, Nicholas Kwiatkowski, Rosella Marullo, M Nieves Calvo-Vidal, Jude Phillip, Benet Pera, Shao Ning Yang, Kaipol Takpradit, Lidia Roman, Marcello Gaudiano, Ramona Crescenzo, Jia Ruan, Giorgio Inghirami, Tinghu Zhang, Graciela Cremaschi, Nathanael S Gray, Leandro Cerchietti
Peripheral T-cell lymphomas (PTCL) are aggressive diseases with poor response to chemotherapy and dismal survival. Identification of effective strategies to target PTCL biology represents an urgent need. Here we report that PTCL are sensitive to transcription-targeting drugs, and, in particular, to THZ1, a covalent inhibitor of cyclin-dependent kinase 7 (CDK7). The STAT-signalling pathway is highly vulnerable to THZ1 even in PTCL cells that carry the activating STAT3 mutation Y640F. In mutant cells, CDK7 inhibition decreases STAT3 chromatin binding and expression of highly transcribed target genes like MYC, PIM1, MCL1, CD30, IL2RA, CDC25A and IL4R...
January 30, 2017: Nature Communications
https://www.readbyqxmd.com/read/28087315/assessing-light-independent-effects-of-hypericin-on-cell-viability-ultrastructure-and-metabolism-in-human-glioma-and-endothelial-cells
#8
Veronika Huntosova, Marta Novotova, Zuzana Nichtova, Lucia Balogova, Maria Maslanakova, Dana Petrovajova, Katarina Stroffekova
Cell exposure to light-independent effects of photosensitizers (PS) used in PDT is clinically relevant when PS affect the pro-apoptotic cascade. In many malignant cells, Hypericin (Hyp) has PS displayed light-dependent anti-proliferative and cytotoxic effects with no cytotoxicity in the dark. Recent studies have shown that Hyp also exhibited light-independent cytotoxic effects in a wide range of concentrations. The molecular mechanisms underlying Hyp light-independent (dark) toxicity may be due to its interaction with different molecules at the Hyp accumulation sites including mitochondria, and these mechanisms are not understood in detail...
January 10, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28076420/chaperone-mediated-autophagy-protein-bag3-negatively-regulates-ebola-and-marburg-vp40-mediated-egress
#9
Jingjing Liang, Cari A Sagum, Mark T Bedford, Sachdev S Sidhu, Marius Sudol, Ziying Han, Ronald N Harty
Ebola (EBOV) and Marburg (MARV) viruses are members of the Filoviridae family which cause outbreaks of hemorrhagic fever. The filovirus VP40 matrix protein is essential for virus assembly and budding, and its PPxY L-domain motif interacts with WW-domains of specific host proteins, such as Nedd4 and ITCH, to facilitate the late stage of virus-cell separation. To identify additional WW-domain-bearing host proteins that interact with VP40, we used an EBOV PPxY-containing peptide to screen an array of 115 mammalian WW-domain-bearing proteins...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28070108/pathway-of-3-mcpd-induced-apoptosis-in-human-embryonic-kidney-cells
#10
Jian Ji, Pei Zhu, Chao Sun, Jiadi Sun, Lu An, Yinzhi Zhang, Xiulan Sun
3-Chloropropane-1,2-diol (3-MCPD) is a heat-produced contaminant formed during the preparation of soy sauce worldwide. The present investigation was conducted to determine the molecular aspects of 3-MCPD toxicity on human embryonic kidney cells (HEK293). Cell viability and apoptosis were assessed in response to exposure to 3-MCPD using the MTT assay and high-content screening (HCS). DNA damage, intracellular reactive oxygen species (ROS) and apoptosis-related proteins were evaluated. Genes related with apoptosis were detected by qPCR-array for further understanding the 3-MCPD induced cell apoptosis signaling pathway...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28064040/bax-to-basics-how-the-bcl2-gene-family-controls-the-death-of-retinal-ganglion-cells
#11
REVIEW
Margaret E Maes, Cassandra L Schlamp, Robert W Nickells
Retinal ganglion cell (RGC) death is the principal consequence of injury to the optic nerve. For several decades, we have understood that the RGC death process was executed by apoptosis, suggesting that there may be ways to therapeutically intervene in this cell death program and provide a more direct treatment to the cells and tissues affected in diseases like glaucoma. A major part of this endeavor has been to elucidate the molecular biological pathways active in RGCs from the point of axonal injury to the point of irreversible cell death...
January 4, 2017: Progress in Retinal and Eye Research
https://www.readbyqxmd.com/read/28053206/gsk3b-mediated-phosphorylation-of-mcl1-regulates-axonal-autophagy-to-promote-wallerian-degeneration
#12
Shuji Wakatsuki, Shinji Tokunaga, Megumi Shibata, Toshiyuki Araki
Macroautophagy is a catabolic process, in which portions of cytoplasm or organelles are delivered to lysosomes for degradation. Emerging evidence has indicated a pathological connection between axonal degeneration and autophagy. However, the physiological function and induction mechanism of autophagy in axons remain elusive. We herein show that, through activation of BECLIN1, glycogen synthase kinase 3B (GSK3B)-mediated phosphorylation of BCL2 family member MCL1 induces axonal autophagy and axonal degeneration...
February 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28049506/novel-derivative-of-aminobenzenesulfonamide-3c-induces-apoptosis-in-colorectal-cancer-cells-through-ros-generation-and-inhibits-cell-migration
#13
Khayal Al-Khayal, Ahmed Alafeefy, Mansoor-Ali Vaali-Mohammed, Amer Mahmood, Ahmed Zubaidi, Omar Al-Obeed, Zahid Khan, Maha Abdulla, Rehan Ahmad
BACKGROUND: Colorectal cancer (CRC) is the 3(rd) most common type of cancer worldwide. New anti-cancer agents are needed for treating late stage colorectal cancer as most of the deaths occur due to cancer metastasis. A recently developed compound, 3c has shown to have potent antitumor effect; however the mechanism underlying the antitumor effect remains unknown. METHODS: 3c-induced inhibition of proliferation was measured in the absence and presence NAC using MTT in HT-29 and SW620 cells and xCELLigence RTCA DP instrument...
January 3, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28040547/lemur-tyrosine-kinase-2-lmtk2-is-a-determinant-of-cell-sensitivity-to-apoptosis-by-regulating-the-levels-of-the-bcl2-family-members
#14
Annalisa Conti, Maria Teresa Majorini, Enrico Fontanella, Alberto Bardelli, Mauro Giacca, Domenico Delia, Miguel Mano, Daniele Lecis
Using a high-throughput approach, we identified lemur tyrosine kinase 2 (LMTK2) as a novel determinant of cell sensitivity to TRAIL. LMTK2 is a poorly characterized serine/threonine kinase believed to play a role in endosomal membrane trafficking and neuronal physiology, and recently found to be mutated in diverse tumor types. We show that LMTK2 silencing sensitizes immortalized epithelial cells and cancer cells to TRAIL, and this phenomenon is accompanied by changes in the expression of BCL2 family members...
December 29, 2016: Cancer Letters
https://www.readbyqxmd.com/read/28039357/key-survival-factor-mcl-1-correlates-with-sensitivity-to-combined-bcl-2-bcl-xl-blockade
#15
Michelle Williams, Linus Lee, Donna J Hicks, Meghan M Joly, David Elion, Bushra Rahman, Courtney McKernan, Violeta Sanchez, Justin M Balko, Thomas Stricker, Monica Valeria Estrada, Rebecca S Cook
: An estimated 40,000 deaths will be attributed to breast cancer in 2016, underscoring the need for improved therapies. Evading cell death is a major hallmark of cancer, driving tumor progression and therapeutic resistance. To evade apoptosis, cancers use anti-apoptotic Bcl-2 proteins to bind to and neutralize apoptotic activators, such as Bim. Investigation of anti-apoptotic Bcl-2 family members in clinical breast cancer datasets, revealed greater expression and more frequent gene amplification of MCL1 as compared to BCL2 or BCL2L1 (Bcl-xL) across three major molecular breast cancer subtypes, Luminal (A and B), HER2-enriched, and Basal-like...
December 30, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28035374/activation-of-oncogenic-pathways-in-classical-hodgkin-lymphoma-by-decitabine-a-rationale-for-combination-with-small-molecular-weight-inhibitors
#16
Tatjana Maria Swerev, Thomas Wirth, Alexey Ushmorov
DNA methylation is an epigenetic control mechanism that contributes to the specific phenotype and to the oncogenic program of virtually all tumor entities. Although efficacy of demethylating agents in classical Hodgkin lymphoma (cHL) was not specifically tested, a case of regression of relapsed metastatic cHL was described as a fortunate side‑effect of the demethylating agent 5‑azacytidine in a patient with myelodysplastic syndrome. We investigated molecular mechanisms of decitabine (5‑Aza‑dC) antitumor activity in cHL using gene expression profiling followed by gene set enrichment analysis...
February 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28018211/cistanche-tubulosa-protects-dopaminergic-neurons-through-regulation-of-apoptosis-and-glial-cell-derived-neurotrophic-factor-in-vivo-and-in-vitro
#17
Qian Xu, Wen Fan, Shui-Fen Ye, Yi-Bo Cong, Wei Qin, Shi-Ya Chen, Jing Cai
Parkinson's disease (PD) is a neurodegenerative disease with the pathological hallmark of reduced nigrostriatal dopamine. In traditional Chinese medicine (TCM) clinical practice, the nanopowder of Cistanche tubulosa has therapeutic effects on PD. To identify the therapeutic mechanism, this study tested the protective effect of different doses of MPP(+)-induced toxicity in MES23.5 cells using the MTT assay and in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice (vehicles). Immunohistochemistry was used to assess cytomorphology and tyrosine hydroxylase (TH) expression...
2016: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28012060/adipocyte-microenvironment-promotes-bclxl-expression-and-confers-chemoresistance-in-ovarian-cancer-cells
#18
Carlos Cardenas, Michele K Montagna, Mary Pitruzzello, Eydis Lima, Gil Mor, Ayesha B Alvero
Resistance to mitochondria-initiated apoptosis is a hallmark of chemoresistant cancer stem cells including CD44+/MyD88+ epithelial ovarian cancer (EOC) stem cells. This is controlled by members of the Bcl2 family of proteins, which function as rheostats of mitochondrial stability. We observed a differential expression profile of Bcl2 family members comparing the chemoresistant EOC stem cells and the chemosensitive CD44-/MyD88- EOC cells. Chemoresistant EOC stem cells surprisingly express higher levels of the pro-apoptotic members Bak and Bax compared to the chemosensitive EOC cells...
December 23, 2016: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/27990281/mitochondrial-apoptosis-and-bh3-mimetics
#19
REVIEW
Haiming Dai, X Wei Meng, Scott H Kaufmann
The BCL2-selective BH3 mimetic venetoclax was recently approved for the treatment of relapsed, chromosome 17p-deleted chronic lymphocytic leukemia (CLL) and is undergoing extensive testing, alone and in combination, in lymphomas, acute leukemias, and solid tumors. Here we summarize recent advances in understanding of the biology of BCL2 family members that shed light on the action of BH3 mimetics, review preclinical and clinical studies leading to the regulatory approval of venetoclax, and discuss future investigation of this new class of antineoplastic agent...
2016: F1000Research
https://www.readbyqxmd.com/read/27974319/microrna-30e-targets-bnip3l-to-protect-against-aldosterone-induced-podocyte-apoptosis-and-mitochondrial-dysfunction
#20
Yan Guo, Xu Deng, Shuang Chen, Lingyun Yang, Jiajia Ni, Rong Wang, Jiajuan Lin, Mi Bai, Zhanjun Jia, Songming Huang, Aihua Zhang
MicroRNAs (miRNAs) are essential for the maintenance of podocyte homeostasis. Emerging evidence demonstrated a protective role of miRNA-30a, a member of miR-30 family in podocyte injury. However, the role of other members of miR-30 family in podocyte injury is unclear. The present study was undertaken to investigate the contribution of miR-30e in the pathogenesis of podocyte injury induced by aldosterone (Aldo), as well as the underlying mechanism. Following Aldo treatment, miR-30e was dose-and time-dependently reduced...
December 14, 2016: American Journal of Physiology. Renal Physiology
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