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https://www.readbyqxmd.com/read/28105281/n-1-benzyl-3-5-dimethyl-1h-pyrazol-4-yl-benzamides-antiproliferative-activity-and-effects-on-mtorc1-and-autophagy
#1
Teng Ai, Rose Willett, Jessica Williams, Rui Ding, Daniel J Wilson, Jiashu Xie, Do-Hyung Kim, Rosa Puertollano, Liqiang Chen
Guided by antiproliferative activity in MIA PaCa-2 cells, we have performed preliminary structure-activity relationship studies on N-(1-benzyl-3,5-dimethyl-1H-pyrazol-4-yl)benzamides. Two selected compounds showed submicromolar antiproliferative activity and good metabolic stability. Both compounds reduced mTORC1 activity and increased autophagy at the basal level. In addition, they disrupted autophagic flux by interfering with mTORC1 reactivation and clearance of LC3-II under starvation/refeed conditions, as evidenced by accumulation of LC3-II and abnormal LC3 labeled punctae...
January 12, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28103582/ampk-autophagy-inhibition-sensitizes-icaritin-induced-anti-colorectal-cancer-cell-activity
#2
Chunxian Zhou, Jun Gu, Gang Zhang, Da Dong, Qunying Yang, Min-Bin Chen, Dongfeng Xu
The current research studied the potential effect of autophagy on icaritin-induced anti-colorectal cancer (CRC) cell activity. Treatment of icaritin in both primary and established (HT-29) CRC cells induced feedback activation of autophagy, evidenced by p62 degradation, Beclin-1 and autophagy-related gene-5 (ATG-5) upregulation, as well as light chain 3B (LC3B)-GFP puncta formation. Pharmacological inhibiting of autophagy dramatically potentiated icaritin-induced CRC cell death and apoptosis. Meanwhile, shRNA-mediated knockdown of Beclin-1 or ATG-5 also sensitized icaritin-induced CRC cell death and apoptosis...
January 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28100648/multi-scale-structural-analysis-of-plant-er-pm-contact-sites
#3
Heather E McFarlane, Eun Kyoung Lee, Laura S van Bezouwen, Bradford Ross, Abel Rosado, A Lacey Samuels
Membrane contact sites (MCS) are recognized across eukaryotic systems as important nanostructures. Endoplasmic reticulum (ER)-plasma membrane (PM) contact sites (EPCS) are involved in excitation-contraction coupling, signalling, and plant responses to stress. In this report, we perform a multi-scale structural analysis of Arabidopsis EPCS that combine live cell imaging, quantitative transmission electron microscopy (TEM), and electron tomography over a developmental gradient. To place EPCS in the context of the entire cortical ER, we examined GFP-HDEL in living cells over a developmental gradient, then SYT1-GFP was used as a specific marker of EPCS...
January 18, 2017: Plant & Cell Physiology
https://www.readbyqxmd.com/read/28097654/melanopsin-expressing-ganglion-cells-in-human-retina-morphology-distribution-and-synaptic-connections
#4
Subha Nasir-Ahmad, Sammy C S Lee, Paul R Martin, Ulrike Grünert
Melanopsin-expressing retinal ganglion cells are intrinsically photosensitive cells that are involved in non-image forming visual processes such as the pupillary light reflex and circadian entrainment but also contribute to visual perception. Here we used immunohistochemistry to study the morphology, density, distribution and synaptic connectivity of melanopsin-expressing ganglion cells in four post mortem human donor retinas. Two types of melanopsin-expressing ganglion cells were distinguished based on their dendritic stratification near either the outer or the inner border of the inner plexiform layer...
January 18, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28095639/early-involvement-of-lysosome-dysfunction-in-the-degeneration-of-cerebral-cortical-neurons-caused-by-the-lipid-peroxidation-product-4-hydroxynonenal
#5
Shi Zhang, Erez Eitan, Mark P Mattson
Free radical-mediated oxidative damage to proteins, lipids and DNA occurs in neurons during acute brain injuries and in neurodegenerative disorders. Membrane lipid peroxidation contributes to neuronal dysfunction and death, in part by disrupting neuronal ion homeostasis and cellular bioenergetics. Emerging findings suggest that 4-hydroxynonenal (HNE), an aldehyde produced during lipid peroxidation, impairs the function of various proteins involved in neuronal homeostasis. Here we tested the hypothesis that HNE impairs the cellular system that removes damaged proteins and organelles, the autophagy - lysosome pathway in rat primary cortical neurons...
January 17, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28077712/changes-in-properties-of-auditory-nerve-synapses-following-conductive-hearing-loss
#6
Xiaowen Zhuang, Wei Sun, Matthew A Xu-Friedman
: Auditory activity plays an important role in the development of the auditory system. Decreased activity can result from conductive hearing loss (CHL) associated with otitis media, which may lead to long-term perceptual deficits. The effects of CHL have been mainly studied at later stages of the auditory pathway, but early stages remain less examined. However, changes in early stages could be important because they would affect how information about sounds is conveyed to higher-order areas for further processing and localization...
January 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28077445/human-antiviral-protein-ifix-suppresses-viral-gene-expression-during-hsv-1-infection-and-is-counteracted-by-virus-induced-proteasomal-degradation
#7
Marni S Crow, Ileana M Cristea
The interferon inducible protein X (IFIX), a member of the PYHIN family, was recently recognized as an antiviral factor against infection with herpes simplex virus 1 (HSV-1). IFIX binds viral DNA upon infection and promotes antiviral cytokines expression. How IFIX exerts its host defense functions and whether it is inhibited by the virus remains unknown. Here, we integrated live cell microscopy, proteomics, IFIX domain characterization, and molecular virology to investigate IFIX regulation and antiviral functions during HSV-1 infection...
January 11, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28077330/dehydropachymic-acid-decreases-bafilomycin-a1-induced-%C3%AE-amyloid-accumulation-in-pc12-cells
#8
Mengyao Yu, Xiaoyan Xu, Nan Jiang, Wei Wei, Fang Li, Liming He, Xia Luo
ETHNOPHARMACOLOGICAL RELEVANCE: Fuling, the sclerotium of Poria cocos, was frequently used in traditional Chinese medicine (TCM) formulae for Alzheimer's disease (AD) intervention over the past 10 centuries. And its extracts exhibited significant effects in both cellular and animal models of AD in previous studies. However, its mechanisms on prevention and treatment of AD have not been well elucidated yet. AIM OF THE STUDY: To investigate the effect and corresponding mechanisms of dehydropachymic acid, which is one of the major triterpenes in Poria cocos, on the clearance of β-Amyloid accumulation in bafilomycin A1 induced PC12 cells...
January 7, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28074037/developmental-pruning-of-excitatory-synaptic-inputs-to-parvalbumin-interneurons-in-monkey-prefrontal-cortex
#9
Daniel W Chung, Zachary P Wills, Kenneth N Fish, David A Lewis
Working memory requires efficient excitatory drive to parvalbumin-positive (PV) interneurons in the primate dorsolateral prefrontal cortex (DLPFC). Developmental pruning eliminates superfluous excitatory inputs, suggesting that working memory maturation during adolescence requires pruning of excitatory inputs to PV interneurons. Therefore, we tested the hypothesis that excitatory synapses on PV interneurons are pruned during adolescence. The density of excitatory synapses, defined by overlapping vesicular glutamate transporter 1-positive (VGlut1+) and postsynaptic density 95-positive (PSD95+) puncta, on PV interneurons was lower in postpubertal relative to prepubertal monkeys...
January 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28069429/the-nuclear-rna-binding-protein-rbp33-influences-mrna-and-spliced-leader-rna-abundance-in-trypanosoma-brucei
#10
Olivera Cirovic, Roman Trikin, Anneliese Hoffmann, Nicholas Doiron, Martin Jakob, Torsten Ochsenreiter
RNA recognition motif (RRM) containing proteins are important regulators of gene expression in trypanosomes. Here we expand our current knowledge on the exclusively nuclear localized RRM domain containing protein RBP33 of Trypanosoma brucei. Overexpression of RBP33 leads to a quick growth arrest in G2/M in bloodstream form cells likely due to an overall mRNA- and spliced leader abundance decrease while the ribosomal RNAs remain unaffected. The recombinant RBP33 binds to poly(A) and random sequence RNA in vitro confirming its role as a RNA binding protein...
January 6, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28063998/inhibiting-ros-nf-%C3%AE%C2%BAb-dependent-autophagy-enhanced-brazilin-induced-apoptosis-in-head-and-neck-squamous-cell-carcinoma
#11
Zhi-Jing He, Fei-Ya Zhu, Shi-Sheng Li, Liang Zhong, Hong-Yu Tan, Kai Wang
Autophagy modulation has been considered a potential therapeutic strategy for head and neck squamous cell carcinoma (HNSCC). A previous study confirmed that brazilin might possess significant anti-carcinogenic activity. However, whether brazilin induces autophagy and its roles in cell death in HNSCC are still unclear. In this study, we have shown that brazilin induced significant apoptosis in the Cal27 HNSCC cell line but not in oral keratinocyte cell line (OKC). In addition to showing apoptosis induction, we demonstrated the brazilin-induced autophagic response in the Cal27 cells, as evidenced by the formation of GFP-LC3 puncta, and also showed the upregulation of LC3-II and Beclin-1...
January 4, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28059587/metabolic-effects-of-fasting-on-human-and-mouse-blood-in-vivo
#12
Federico Pietrocola, Yohann Demont, Francesca Castoldi, David Enot, Sylvère Durand, Michaela Semeraro, Elisa Elena Baracco, Jonathan Pol, Jose Manuel Bravo-San Pedro, Chloé Bordenave, Sarah Levesque, Juliette Humeau, Alexis Chery, Didier Métivier, Frank Madeo, M Chiara Maiuri, Guido Kroemer
Starvation is a strong physiological stimulus of macroautophagy/autophagy. In this study, we addressed the question as to whether it would be possible to measure autophagy in blood cells after nutrient deprivation. Fasting of mice for 48 h (which causes ∼20% weight loss) or starvation of human volunteers for up to 4 days (which causes <2% weight loss) provokes major changes in the plasma metabolome, yet induces only relatively minor alterations in the intracellular metabolome of circulating leukocytes...
January 6, 2017: Autophagy
https://www.readbyqxmd.com/read/28058015/vitamin-d-differentially-regulates-salmonella-induced-intestine-epithelial-autophagy-and-interleukin-1%C3%AE-expression
#13
Fu-Chen Huang
AIM: To investigate the effects of active vitamin D3 on autophagy and interleukin (IL)-1β expression in Salmonella-infected intestinal epithelial cells (IECs). METHODS: Caco-2 cells, NOD2 siRNA-, Atg16L1 siRNA- or vitamin D receptor (VDR) siRNA-transfected Caco-2 cells were pretreated with 1,25-dihydroxyvitamin D3 (1,25D3), and then infected by wild-type S. typhimurium strain SL1344. The conversion of LC3-I to LC3-II was detected by Western blot analysis and LC3(+) autophagosome was analyzed by immunofluorescence...
December 21, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28055007/dysfunctional-autophagy-in-rpe-a-contributing-factor-in-age-related-macular-degeneration
#14
Nady Golestaneh, Yi Chu, Yang-Yu Xiao, Gianna L Stoleru, Alexander C Theos
Age-related macular degeneration (AMD) is a devastating neurodegenerative disease and a major cause of blindness in the developed world. Owing to its complexity and the lack of an adequate human model that recapitulates key aspects of the disease, the molecular mechanisms of AMD pathogenesis remain poorly understood. Here we show that cultured human retinal pigment epithelium (RPE) from AMD donors (AMD RPE) are functionally impaired and exhibit distinct phenotypes compared with RPE cultured from normal donors (normal RPE)...
January 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28050794/heterogeneity-in-synaptogenic-profile-of-astrocytes-from-different-brain-regions
#15
Andrea Schmidt Buosi, Isadora Matias, Ana Paula Bergamo Araujo, Carolina Batista, Flávia Carvalho Alcantara Gomes
Astrocytes, the most abundant glial cells in the central nervous system (CNS), comprise a heterogeneous population of cells. However, how this heterogeneity impacts their function within brain homeostasis and response to injury and disease is still largely unknown. Recently, astrocytes have been recognized as important regulators of synapse formation and maturation. Here, we analyzed the synaptogenic property of astrocytes from different regions of the CNS. The effect of conditioned medium derived from astrocytes (astrocyte-conditioned medium (ACM)) from cerebral cortex, hippocampus, midbrain and cerebellum, in synapse formation, was evaluated...
January 3, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28026004/ethanol-enhances-thymocyte-apoptosis-and-autophagy-in-macrophages-of-rat-thymi
#16
Tsubasa Betsuyaku, Nabil Eid, Yuko Ito, Yoshihisa Tanaka, Yoshinori Otsuki, Yoichi Kondo
Tingible body macrophages (TBMs) play essential roles in the phagocytosis of apoptotic lymphocytes, specifically under exposure to various stressors. Although excessive ethanol consumption may enhance thymocyte apoptosis, reports investigating the autophagic response of the thymus to ethanol toxicity are still lacking. We investigated apoptosis and autophagy in thymi of an animal model of binge ethanol exposure. Adult male Wistar rats were injected intraperitoneally either with 5 g/kg ethanol or phosphate buffer saline (for the control group) and sacrificed 0, 3, 6 and 24 hours after injection...
December 27, 2016: Histology and Histopathology
https://www.readbyqxmd.com/read/28007915/podosome-assembly-is-controlled-by-the-gtpase-arf1-and-its-nucleotide-exchange-factor-arno
#17
Nisha Bte Mohd Rafiq, Zi Zhao Lieu, Tingting Jiang, Cheng-Han Yu, Paul Matsudaira, Gareth E Jones, Alexander D Bershadsky
Podosomes represent a class of integrin-mediated cell-matrix adhesions formed by migrating and matrix-degrading cells. We demonstrate that in macrophage-like THP1 cells and fibroblasts stimulated to produce podosomes, down-regulation of the G-protein ARF1 or the ARF1 guanine nucleotide exchange factor, ARNO, by small, interfering RNA or pharmacological inhibitors led to striking podosome elimination. Concomitantly, treatments inducing podosome formation increased the level of guanosine triphosphate (GTP)-bound ARF1...
January 2, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/27997694/spatial-patterning-of-excitatory-and-inhibitory-neuropil-territories-during-spinal-circuit-development
#18
Qing Yan, Lu Zhai, Bo Zhang, Julia E Dallman
To generate rhythmic motor behaviors, both single neurons and neural circuits require a balance between excitatory inputs that trigger action potentials and inhibitory inputs that promote a stable resting potential (E/I balance). Previous studies have focused on individual neurons and have shown that, over a short spatial scale, excitatory and inhibitory (E/I) synapses tend to form structured territories with inhibitory inputs enriched on cell bodies and proximal dendrites and excitatory inputs on distal dendrites...
December 20, 2016: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/27994511/autophagy-activation-protects-shock-wave-induced-renal-tubular-epithelial-cell-apoptosis-may-through-modulation-of-akt-gsk-3%C3%AE-pathway
#19
Qingzhi Long, Xiang Li, Hui He, Dalin He
PURPOSE: Extracorporeal shock wave lithotripsy (ESWL) is well documented to exert destructive effect to renal cells and its mechanism is not clear. Autophagy is one of cell basic response for stressful conditions and it is important to determine cell's fate. The aim of this study is to elucidate the role of autophagy in the process of shock wave-induced renal cells injury. METHODS: NRK-52E cell, a rat renal tubular epithelial cell, was exposed to shock wave at the voltage of 14KV...
2016: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/27987205/mid-life-environmental-enrichment-increases-synaptic-density-in-ca1-in-a-mouse-model-of-a%C3%AE-associated-pathology-and-positively-influences-synaptic-and-cognitive-health-in-healthy-ageing
#20
Kimberley E Stuart, Anna E King, Carmen M Fernandez-Martos, Justin Dittmann, Mathew J Summers, James C Vickers
Early-life cognitive enrichment may reduce the risk of experiencing cognitive deterioration and dementia in later-life. However, an intervention to prevent or delay dementia is likely to be taken up in mid to later-life. Hence, we investigated the effects of environmental enrichment in wildtype mice and in a mouse model of Aβ neuropathology (APPSWE /PS1dE9 ) from 6 months of age. After 6 months of housing in standard laboratory cages, APPSWE /PS1dE9 (n = 27) and healthy wildtype (n = 21) mice were randomly assigned to either enriched or standard housing...
December 17, 2016: Journal of Comparative Neurology
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