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https://www.readbyqxmd.com/read/28713020/pneumolysin-induced-autophagy-contributes-to-inhibition-of-osteoblast-differentiation-through-downregulation-of-sp1-in-human-osteosarcoma-cells
#1
Jinwook Kim, Hee-Weon Lee, Dong Kwon Rhee, James C Paton, Suhkneung Pyo
BACKGROUND INFORMATION: The 53kDa protein pneumolysin (PLY) is the main virulence factor of Streptococcus pneumoniae, a leading cause of invasive pneumococcal diseases. PLY forms pores in cholesterol-containing membranes, thereby interfering with the function of cells. Bone destruction is a serious matter in chronic inflammatory diseases such as septic arthritis and osteomyelitis. S. pneumoniae is increasingly being recognized as a common cause of septic arthritis, but its pathogenesis is poorly defined...
July 13, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28703806/inhibition-of-autophagy-as-a-treatment-strategy-for-p53-wild-type-acute-myeloid-leukemia
#2
Hendrik Folkerts, Susan Hilgendorf, Albertus T J Wierenga, Jennifer Jaques, André B Mulder, Paul J Coffer, Jan Jacob Schuringa, Edo Vellenga
Here we have explored whether inhibition of autophagy can be used as a treatment strategy for acute myeloid leukemia (AML). Steady-state autophagy was measured in leukemic cell lines and primary human CD34(+) AML cells with a large variability in basal autophagy between AMLs observed. The autophagy flux was higher in AMLs classified as poor risk, which are frequently associated with TP53 mutations (TP53(mut)), compared with favorable- and intermediate-risk AMLs. In addition, the higher flux was associated with a higher expression level of several autophagy genes, but was not affected by alterations in p53 expression by knocking down p53 or overexpression of wild-type p53 or p53(R273H)...
July 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28703297/neither-eosinophils-nor-neutrophils-require-atg5-dependent-autophagy-for-extracellular-dna-trap-formation
#3
Nina Germic, Darko Stojkov, Kevin Oberson, Shida Yousefi, Hans-Uwe Simon
The importance of extracellular traps (ETs) in innate immunity is well established, but the molecular mechanisms responsible for their formation remain unclear and in scientific dispute. ETs have been defined as extracellular DNA scaffolds associated with the granule proteins of eosinophils or neutrophils. They are capable of killing bacteria extracellularly. Based mainly on results with phosphoinositide 3-kinase (PI3K) inhibitors such as 3-methyladenine (3-MA) and wortmannin which are commonly used to inhibit autophagy, several groups have reported that autophagy is required for neutrophil extracellular trap (NET) formation...
July 13, 2017: Immunology
https://www.readbyqxmd.com/read/28699257/effects-of-ochratoxin-a-on-er-stress-mapk-signaling-pathway-and-autophagy-of-kidney-and-spleen-in-pigs
#4
Fang Gan, Lili Hou, Yajiao Zhou, Yunhuan Liu, Da Huang, Xingxiang Chen, Kehe Huang
Ochratoxin A (OTA), a worldwide mycotoxin found in food and feeds, is a potent nephrotoxin and immunotoxin in animals and humans. This research was conducted to evaluate whether endoplasmic reticulum (ER) stress, MAPK signaling pathway and autophagy were induced by OTA in kidney and spleen of pigs. Twenty-seven crossbred pigs randomly allocated to 3 groups were fed for 42 days ad libitum a basal diet without (Con group, 0.00 μg OTA/kg) and with supplementation of OTA at 400 (OTA-L group) and 800 μg/kg (OTA-H group)...
July 12, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28696570/effects-of-combined-lysosomal-and-mitochondrial-photodamage-in-a-non-small-cell-lung-cancer-cell-line-the-role-of-paraptosis
#5
David Kessel, John J Reiners
We previously reported that a low-level of lysosomal photodamage potentiated the phototoxic effect of subsequent mitochondrial photodamage mediated by the benzoporphyrin derivative BPD in murine hepatoma 1c1c7 cells. This was attributed to release of Ca(2+) from damaged lysosomes and a calpain-mediated conversion of the autophagy-related protein ATG5 to a pro-apoptotic fragment. We now report a comparison of these results with those obtained with the human non small-cell lung cancer A549 cell line. A549 cells contained lower levels of ATG5 and were less responsive than 1c1c7 cultures to the PDT combination...
July 11, 2017: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/28696297/mtorc1-activates-srebp-2-by-suppressing-cholesterol-trafficking-to-lysosomes-in-mammalian-cells
#6
Walaa Eid, Kristin Dauner, Kevin C Courtney, AnneMarie Gagnon, Robin J Parks, Alexander Sorisky, Xiaohui Zha
mTORC1 is known to activate sterol regulatory element-binding proteins (SREBPs) including SREBP-2, a master regulator of cholesterol synthesis. Through incompletely understood mechanisms, activated mTORC1 triggers translocation of SREBP-2, an endoplasmic reticulum (ER) resident protein, to the Golgi where SREBP-2 is cleaved to translocate to the nucleus and activate gene expression for cholesterol synthesis. Low ER cholesterol is a well-established trigger for SREBP-2 activation. We thus investigated whether mTORC1 activates SREBP-2 by reducing cholesterol delivery to the ER...
July 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28695958/identification-and-characterization-of-the-autophagy-related-genes-atg12-and-atg5-in-hydra
#7
Nishikant S Dixit, Bhupendra V Shravage, Surendra Ghaskadbi
Autophagy is an evolutionarily conserved process in eukaryotic cells that is involved in the degradation of cytoplasmic contents including organelles via the lysosome. Hydra is an early metazoan which exhibits simple tissue grade organization, a primitive nervous system, and is one of the classical non-bilaterian models extensively used in evo-devo research. Here, we describe the characterization of two core autophagy genes, Atg12 and Atg5, from hydra. In silico analyses including sequence similarity, domain analysis, and phylogenetic analysis demonstrate the conservation of these genes across eukaryotes...
2017: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/28694294/bacteroides-fragilis-enterotoxin-induces-the-formation-of-autophagosomes-in-endothelial-cells-but-interferes-their-autophagosomal-fusion-with-lysosomes-for-complete-autophagic-flux-through-a-mitogen-activated-protein-kinase-ap-1-and-c-ebp-homologous-protein
#8
Su Hyuk Ko, Jong Ik Jeon, Hyun Soo Myung, Young-Jeon Kim, Jung Mogg Kim
Bacteroides fragilis enterotoxin (BFT), a virulence factor of enterotoxigenic B. fragilis (ETBF), plays an essential role in mucosal inflammation. Although autophagy contributes to the pathogenesis of diverse infectious diseases, little is known about autophagy in ETBF infection. This study was conducted to investigate the role of BFT in the autophagic process in endothelial cells (ECs). Stimulation of human umbilical vein ECs (HUVECs) with BFT increased LC3-II conversion from LC3-I and protein expression of p62, Atg5 and Atg12...
July 10, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28693471/spatial-pattern-analysis-of-nuclear-migration-in-remodelled-muscles-during-drosophila-metamorphosis
#9
Kuleesha, Lin Feng, Martin Wasser
BACKGROUND: Many human muscle wasting diseases are associated with abnormal nuclear localization. During metamorphosis in Drosophila melanogaster, multi-nucleated larval dorsal abdominal muscles either undergo cell death or are remodeled to temporary adult muscles. Muscle remodeling is associated with anti-polar nuclear migration and atrophy during early pupation followed by polar migration and muscle growth during late pupation. Muscle remodeling is a useful model to study genes involved in myonuclear migration...
July 10, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28692436/andrographolide-enhances-cisplatin-mediated-anticancer-effects-in-lung-cancer-cells-through-blockade-of-autophagy
#10
Daolu Yuwen, Shanwei Mi, Yuzhu Ma, Wenjie Guo, Qiang Xu, Yan Shen, Yongqian Shu
Lung cancer is the most common cause of cancer-related death worldwide and the platinum-based drugs such as cisplatin have been used as the first line of the treatment. However, the clinical effectiveness of such chemotherapy is limited by intrinsic or acquired resistance. In this study, we found that cisplatin induced autophagy that attenuated the sensitivity of both A549 and Lewis lung cancer (LLC) cells to cisplatin. In contrast, the clinical drug andrographolide (Andro) suppressed autophagy and enhanced cisplatin-mediated apoptosis in these cells...
July 7, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28690552/the-role-of-reactive-oxygen-species-and-autophagy-in-periodontitis-and-their-potential-linkage
#11
REVIEW
Chengcheng Liu, Longyi Mo, Yulong Niu, Xin Li, Xuedong Zhou, Xin Xu
Periodontitis is a chronic inflammatory disease that causes damage to periodontal tissues, which include the gingiva, periodontal ligament, and alveolar bone. The major cause of periodontal tissue destruction is an inappropriate host response to microorganisms and their products. Specifically, a homeostatic imbalance between reactive oxygen species (ROS) and antioxidant defense systems has been implicated in the pathogenesis of periodontitis. Elevated levels of ROS acting as intracellular signal transducers result in autophagy, which plays a dual role in periodontitis by promoting cell death or blocking apoptosis in infected cells...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28685931/structure-of-the-wd40-domain-of-human-atg16l1
#12
Milica Bajagic, Archna, Petra Büsing, Andrea Scrima
Autophagy-related protein ATG16L1 is a component of the mammalian ATG12∼ATG5/ATG16L1 complex, which acts as E3-ligase to catalyze lipidation of LC3 during autophagosome biogenesis. The N-terminal part of ATG16L1 comprises the ATG5-binding site and coiled-coil dimerization domain, both also present in yeast ATG16 and essential for bulk and starvation induced autophagy. While absent in yeast ATG16, mammalian ATG16L1 further contains a predicted C-terminal WD40-domain, which has been shown to be involved in mediating interaction with diverse factors in the context of alternative functions of autophagy, such as inflammatory control and xenophagy...
July 7, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28685385/exclusive-activation-of-caspase-3-in-mossy-fibers-and-altered-dynamics-of-autophagy-markers-in-the-mice-hippocampus-upon-status-epilepticus-induced-by-kainic-acid
#13
A Rami, A Benz
Epileptic seizures are generally associated with pathological changes in the hippocampus such as astrogliosis, mossy fiber sprouting, and neuronal damage. However, more than 30% of temporal lobe epilepsy in humans shows neither neuronal damage nor mossy fiber sprouting despite chronic epileptic seizures. A similar situation exists in certain commonly used strains of mice, specifically C57BL/6 and BALB/c, which exhibit epileptic seizures, but no neuronal damage upon kainic acid administration. This suggests that intrinsic factors may influence the pathological manifestations of epilepsy...
July 6, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28684853/downregulation-of-atg5-dependent-macroautophagy-by-chaperone-mediated-autophagy-promotes-breast-cancer-cell-metastasis
#14
Qi Han, Youcai Deng, Sha Chen, Rui Chen, Mingzhen Yang, Zhujun Zhang, Xiongshan Sun, Wei Wang, Ying He, Fangjie Wang, Xiaodong Pan, Peng Li, Wenjing Lai, Hongqin Luo, Pei Huang, Xiao Guan, Yafei Deng, Jun Yan, Xianjie Xu, Yan Wen, An Chen, Chuanmin Hu, Xiaohui Li, Shuhui Li
Recent data have shown that the expression of lysosome-associated membrane protein type 2 A (LAMP2A), the key protein in the chaperone-mediated autophagy (CMA) pathway, is elevated in breast tumor tissues. However, the exact effects and mechanisms of CMA during breast cancer metastasis remain largely unknown. In this study, we found that the LAMP2A protein level was significantly elevated in human breast cancer tissues, particularly in metastatic carcinoma. The increased LAMP2A level was also positively correlated with the histologic grade of ductal breast cancer...
July 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28679997/alternative-autophagy-plays-a-central-role-in-mitochondria-elimination-from-reticulocytes
#15
Shigeomi Shimizu
Mitophagy is a mitochondrial quality control mechanism where damaged and surplus mitochondria are degraded by macroautophagy. Mitophagy is associated with various physiological and pathological events such as mitochondrial clearance during the terminal differentiation of reticulocytes. There are two different mammalian autophagy pathways: the Atg5-dependent conventional pathway and Atg5-independent alternative pathway; the latter is involved in reticulocyte's mitophagy.
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28677782/nicd-inhibits-cell-proliferation-and-promotes-apoptosis-and-autophagy-in-pc12-cells
#16
Bo Li, Ping Duan, Xuefei Han, Wenhai Yan, Ying Xing
Pheochromocytoma is a tumor of the adrenal medulla for which surgical resection is the only therapy. Though the Notch1 signaling pathway has been suggested as a target for pheochromocytoma treatment, the effect of Notch1 intracellular domain (NICD) on pheochromocytoma cell growth remains unknown. In the present study, the effect of NICD on pheochromocytoma cell growth was examined, by use of a tetracycline‑inducible system for NICD overexpression in the PC12 pheochromocytoma cell line. Flow cytometry was used to determine the effect of NICD on cell cycle phase distribution and apoptosis in PC12 cells...
June 29, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28671312/anti-prostate-cancer-potential-of-gossypetin-via-inducing-apoptotic-and-autophagic-cell-death
#17
Ming-Shih Lee, Chia-Wen Tsai, Chi-Ping Wang, Jing-Hsien Chen, Hui-Hsuan Lin
Gossypetin (GTIN), a naturally occurring hexahydroxy flavone, has been shown to possess antimutagenic, antioxidant, antimicrobial, and antiatherosclerotic effects. Here, we investigated the mechanism(s) underlying the anticancer potential of GTIN. In this study investigations were showed that GTIN preferentially induces programmed cell death of prostate cancer (PCa) cells in vitro and in vivo. MTT data showed that GTIN exhibited the anti-proliferation effect on human PCa cells in a dose- and time-dependent manner...
July 3, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28669590/tranexamic-acid-inhibits-melanogenesis-by-activating-the-autophagy-system-in-cultured-melanoma-cells
#18
Yeong Hee Cho, Jung Eun Park, Do Sung Lim, Jung Sup Lee
BACKGROUND: As interest in skin beauty increases, the development of new skin whitening agents has attracted substantial attention; however, the action mechanism of the agents developed so far remains largely unknown. Tranexamic acid (TXA) is commonly being used to reduce melanin synthesis in patients with melasma and also used as a raw material for functional whitening cosmetics, although its action mechanism is poorly understood. Autophagy has been well known to be essential for tissue homeostasis, adaptation to starvation, and removal of dysfunctional organelles or pathogens...
June 7, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28665306/standard-immunohistochemical-assays-to-assess-autophagy-in-mammalian-tissue
#19
REVIEW
Wim Martinet, Lynn Roth, Guido R Y De Meyer
Autophagy is a highly conserved lysosomal degradation pathway with major impact on diverse human pathologies. Despite the development of different methodologies to detect autophagy both in vitro and in vivo, monitoring autophagy in tissue via immunohistochemical techniques is hampered due to the lack of biomarkers. Immunohistochemical detection of a punctate pattern of ATG8/MAP1LC3 proteins is currently the most frequently used approach to detect autophagy in situ, but it depends on a highly sensitive detection method and is prone to misinterpretation...
June 30, 2017: Cells
https://www.readbyqxmd.com/read/28661479/ochratoxin-a-induced-autophagy-in-vitro-and-in-vivo-promotes-porcine-circovirus-type-2-replication
#20
Gang Qian, Dandan Liu, Junfa Hu, Fang Gan, Lili Hou, Xingxiang Chen, Kehe Huang
Ochratoxin A (OTA) is a mycotoxin produced by Aspergillus and Penicillium. Porcine circovirus type 2 (PCV2) is recognized as the causative agent of porcine circovirus-associated diseases. Recently, we reported that low doses of OTA promoted PCV2 replication in vitro and in vivo, but the underlying mechanism needed further investigation. The present studies further confirmed OTA-induced PCV2 replication promotion as measured by cap protein expression, viral titer, viral DNA copies and the number of infected cells...
June 29, 2017: Cell Death & Disease
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