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https://www.readbyqxmd.com/read/28231469/bassoon-controls-presynaptic-autophagy-through-atg5
#1
Nathan D Okerlund, Katharina Schneider, Sergio Leal-Ortiz, Carolina Montenegro-Venegas, Sally A Kim, Loren C Garner, Eckart D Gundelfinger, Richard J Reimer, Craig C Garner
Mechanisms regulating the surveillance and clearance of synaptic proteins are not well understood. Intriguingly, the loss of the presynaptic active zone proteins Piccolo and Bassoon triggers the loss of synaptic vesicles (SVs) and compromises synaptic integrity. Here we report that the destruction of SVs in boutons lacking Piccolo and Bassoon was associated with the induction of presynaptic autophagy, a process that depended on poly-ubiquitination, but not the E3 ubiquitin ligase Siah1. Surprisingly, gain or loss of function (LOF) of Bassoon alone suppressed or enhanced presynaptic autophagy, respectively, implying a fundamental role for Bassoon in the local regulation of presynaptic autophagy...
February 22, 2017: Neuron
https://www.readbyqxmd.com/read/28230866/oridonin-induces-autophagy-via-inhibition-of-glucose-metabolism-in-p53-mutated-colorectal-cancer-cells
#2
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/28230791/the-temporal-pattern-flux-and-function-of-autophagy-in-spinal-cord-injury
#3
REVIEW
Kailiang Zhou, Charles A Sansur, Huazi Xu, Xiaofeng Jia
Previous studies have indicated that autophagy plays a critical role in spinal cord injury (SCI), including traumatic spinal cord injury (TSCI) and ischemia-reperfusion spinal cord injury (IRSCI). However, while the understanding of mechanisms underlying autophagy in SCI has progressed, there remain several controversial points: (1) temporal pattern results of autophagic activation after SCI are not consistent across studies; (2) effect of accumulation of autophagosomes due to the blockade or enhancement of autophagic flux is uncertain; (3) overall effect of enhanced autophagy remains undefined, with both beneficial and detrimental outcomes reported in SCI literature...
February 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28230638/mtor-inhibition-cardiovascular-diseases-dyslipidemia-and-atherosclerosis
#4
Ammar Kurdi, Wim Martinet, Guido R Y De Meyer
Inhibitors of the mechanistic target of rapamycin (mTOR) have unique anti-atherosclerotic effects such as depletion of plaque macrophages, induction of autophagy and activation of cholesterol efflux. However, a common side effect of their use is dyslipidemia, a well-known risk factor for atherosclerosis. Indeed, mTOR inhibitors prevent lipid storage, increase LDL cholesterol levels and activate lipolysis. Although the net effect of mTOR inhibition seems favorable, the use of cholesterol lowering drugs to manage dyslipidemia remains the most recommended strategy...
February 23, 2017: Transplantation
https://www.readbyqxmd.com/read/28229934/novel-and-functional-atg12-gene-variants-in-sporadic-parkinson-s-disease
#5
Yuequn Li, Jian Huang, Shuchao Pang, Haihua Wang, Aimei Zhang, Robert G Hawley, Bo Yan
Parkinson's disease (PD) is a common and progressive neurodegenerative disease, including familial and sporadic cases. To date, genetic causes for sporadic PD, majority of PD cases, remain largely unknown. Accumulating evidence indicates that dysfunctional autophagy, a highly conserved cellular process, is involved in the PD pathogenesis. We speculated that changed expression levels of autophagy-related genes (ATG) may contribute to PD development. Previously, we have genetically analyzed ATG5 and ATG7 genes in sporadic PD patients and identified several functional DNA sequence variants (DSVs)...
February 13, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28229902/impact-of-high-glucose-and-ages-on-cultured-kidney-derived-cells-effects-on-cell-viability-lysosomal-enzymes-and-effectors-of-cell-signaling-pathways
#6
Giovani B Peres, Nestor Schor, Yara M Michelacci
We have previously reported decreased expression and activities of lysosomal cathepsins B and L in diabetic kidney. Relevant morphological changes were observed in proximal tubules, suggesting that these cells are implicated in the early stages of the disease. The aim of the present study was to investigate the mechanisms that lead to these changes. The effects of high glucose (HG) and advanced glycation end products (AGEs) on cell viability, lysosomal enzymes and other effectors of cell signaling of cultured kidney cells were studied...
February 13, 2017: Biochimie
https://www.readbyqxmd.com/read/28229532/n-butylidenephthalide-treatment-prolongs-life-span-and-attenuates-motor-neuron-loss-in-sod1-g93a-mouse-model-of-amyotrophic-lateral-sclerosis
#7
Qin-Ming Zhou, Jing-Jing Zhang, Song Li, Sheng Chen, Wei-Dong Le
AIMS: To evaluate the therapeutic effects of n-butylidenephthalide (BP) in SOD1(G93A) mouse model of amyotrophic lateral sclerosis and explore the possible mechanisms. METHODS: The SOD1(G93A) mice were treated by oral administration of BP (q.d., 400 mg/kg d) starting from 60 days of age and continuing until death. The rotarod test was performed to assess the disease onset. The expression levels of apoptosis-related proteins, inflammatory molecules, and autophagy-associated proteins were determined...
February 22, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28229418/measurement-of-autophagy-by-flow-cytometry
#8
Silvia Zappavigna, Angela Lombardi, Gabriella Misso, Anna Grimaldi, Michele Caraglia
Autophagy activation is characterized by the accumulation of double-membrane autophagic vesicles (autophagosomes) in the cytoplasm. The mere presence of autophagosomes in the cytoplasm does not necessarily indicate an increased level of autophagy, since the blockade of any step downstream of autophagosome formation increases the number of autophagosomes. Therefore, quantitative methods for the detection of cytoplasmic protein turnover should be employed in addition to autophagosome monitoring, to verify increased levels of autophagy...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28228415/reduced-skeletal-muscle-fiber-size-following-caloric-restriction-is-associated-with-calpain-mediated-proteolysis-and-attenuation-of-igf-1-signaling
#9
Yue Lu, Jennifer S Bradley, Sarah R McCoski, John M Gonzalez, Alan D Ealy, Sally E Johnson
Caloric restriction decreases skeletal muscle mass in mammals, principally due to a reduction in fiber size. The effect of suboptimal nutrient intake on skeletal muscle metabolic properties in neonatal calves was examined. The longissimus muscle (LM) was collected after 8 wks consuming a control (CON) or caloric restricted (CR) diet and muscle fiber size, gene expression and metabolic signal transduction activity was measured. Results revealed that CR animals had smaller (P < 0.05) LM fiber cross-sectional area than CON, as expected...
February 22, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28228351/autophagy-is-the-key-process-in-the-re-establishment-of-the-epitheloid-phenotype-during-mesenchymal-epithelial-transition-met
#10
Viktória Zsiros, Sándor Katz, Nikolett Dóczi, Anna L Kiss
In previous studies we showed that during Freund's adjuvant induced inflammation rat mesenteric mesothelial cells undergo epithelial-mesenchymal transition type II (EMT). This process was characterized by a dramatic increase of the number of cell organelles and volume of mesothelial cells. After the inflammation reached its maximum, the mesenchymal-like cells gradually regained their epithelial phenotype (mesenchymal-epithelial transition, MET). During the recovery process, the decrease of the number of cell organelles was accompanied by an increasing number of autophagic structures in the cytoplasm, indicating that autophagy might play crucial role in MET...
February 19, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28228270/torc1-inhibits-gsk3-mediated-elo2-phosphorylation-to-regulate-very-long-chain-fatty-acid-synthesis-and-autophagy
#11
Christine Zimmermann, Aline Santos, Kenneth Gable, Sharon Epstein, Charulatha Gururaj, Pierre Chymkowitch, Dennis Pultz, Steven V Rødkær, Lorena Clay, Magnar Bjørås, Yves Barral, Amy Chang, Nils J Færgeman, Teresa M Dunn, Howard Riezman, Jorrit M Enserink
No abstract text is available yet for this article.
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28225130/systematic-investigation-on-the-intracellular-trafficking-network-of-polymeric-nanoparticles
#12
Jinxie Zhang, Danfeng Chang, Yao Yang, Xudong Zhang, Wei Tao, Lijuan Jiang, Xin Liang, Hsiangi Tsai, Laiqiang Huang, Lin Mei
Polymeric nanoparticles such as PLGA-based nanoparticles are emerging as promising carriers for controlled drug delivery. However, little is known about the intracellular trafficking network of polymeric nanoparticles. Here, more than 30 Rab proteins were used as markers of multiple trafficking vesicles in endocytosis, exocytosis and autophagy to investigate in detail the intracellular trafficking pathways of PLGA nanoparticles. We observed that coumarin-6-loaded PLGA nanoparticles were internalized by the cells mainly through caveolin and clathrin-dependent endocytosis and Rab34-mediated macropinocytosis...
February 22, 2017: Nanoscale
https://www.readbyqxmd.com/read/28225086/uvrag-deficiency-exacerbates-doxorubicin-induced-cardiotoxicity
#13
Lin An, Xiao-Wen Hu, Shasha Zhang, Xiaowen Hu, Zongpei Song, Amber Naz, Zhenguo Zi, Jian Wu, Can Li, Yunzeng Zou, Lin He, Hongxin Zhu
Doxorubicin (DOX) is an effective chemotherapeutic drug in the treatment of various types of cancers. However, its clinical application has been largely limited by potential development of cardiotoxicity. Previously we have shown that ultra-violet radiation resistance-associated gene (UVRAG), an autophagy-related protein, is essential for the maintenance of autophagic flux in the heart under physiological conditions. Here, we sought to determine the role of UVRAG-mediated autophagy in DOX-induced cardiotoxicity...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28225005/autophagy-protects-against-palmitic-acid-induced-apoptosis-in-podocytes-in-vitro
#14
Xu-Shun Jiang, Xue-Mei Chen, Jiang-Min Wan, Hai-Bo Gui, Xiong-Zhong Ruan, Xiao-Gang Du
Autophagy is a highly conserved degradation process that is involved in the clearance of proteins and damaged organelles to maintain intracellular homeostasis and cell integrity. Type 2 diabetes is often accompanied by dyslipidemia with elevated levels of free fatty acids (FFAs). Podocytes, as an important component of the filtration barrier, are susceptible to lipid disorders. The loss of podocytes causes proteinuria, which is involved in the pathogenesis of diabetic nephropathy. In the present study, we demonstrated that palmitic acid (PA) promoted autophagy in podocytes...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28224747/why-do-lactobacilli-dominate-the-human-vaginal-microbiota
#15
REVIEW
S S Witkin, I M Linhares
: Lactobacilli are the most abundant vaginal bacteria in women. They inhibit binding of other bacteria to epithelial cells and produce lactic acid that kills or inhibits the growth of many other bacteria. Lactic acid blocks histone deacetylases, thereby enhancing gene transcription and DNA repair. Lactic acid induces autophagy in epithelial cells to degrade intracellular microorganisms and promote homeostasis. Lactobacilli are tolerated by vaginal epithelial cells and inhibit induction of pro-inflammatory cytokines...
March 2017: BJOG: An International Journal of Obstetrics and Gynaecology
https://www.readbyqxmd.com/read/28224619/fl-asparaginase-mediated-downregulation-of-c-myc-promotes-1-25-oh-2-d3-induced-myeloid-differentiation-in-acute-myeloid-leukemia-cells
#16
Ju Han Song, Eunchong Park, Myun Soo Kim, Kyung-Min Cho, Su-Ho Park, Arim Lee, Jiseon Song, Hyeoung-Joon Kim, Jeong-Tae Koh, Tae Sung Kim
Treatment of acute myeloid leukemia (AML) largely depends on chemotherapy, but current regimens have been unsatisfactory for long-term remission. Although differentiation induction therapy utilizing 1,25(OH)2 D3 (VD3) has shown great promise for the improvement of AML treatment efficacy, severe side effects caused by its supraphysiological dose limit its clinical application. Here we investigated the combinatorial effect of l-asparaginase (ASNase)-mediated amino acid depletion and the latent alternation of VD3 activity on the induction of myeloid differentiation...
February 22, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28224423/prognostic-significance-of-autophagy-related-proteins-expression-in-resected-human-gastric-adenocarcinoma
#17
Bing Qu, Lei Yao, Hua-Ling Ma, Hong-Lei Chen, Zhi Zhang, Jiang Xie
Gastric adenocarcinoma (GC) is one of the most common malignancies in the world and one of the most frequent causes of cancer-related death. Autophagy is a highly regulated catabolic pathway responsible for the degradation of long-lived proteins and damaged intracellular organelles. However, the mechanism and guiding significance of autophagy in the development and progression of GC have remained to be elucidated. This study aimed to explore the clinicopathological significances and prognostic values of autophagy-related proteins AMBRA1 and Beclin-1 in GC...
February 2017: Journal of Huazhong University of Science and Technology. Medical Sciences
https://www.readbyqxmd.com/read/28224118/heparin-binding-hemagglutinin-of-mycobacterium-tuberculosis-is-an-inhibitor-of-autophagy
#18
Qing Zheng, Zhi Li, Shan Zhou, Qian Zhang, Lei Zhou, Xiaorui Fu, Liu Yang, Yueyun Ma, Xiaoke Hao
Airway epithelial cell is often the initial site of attack by pathogens, and cell death is commonly caused by internalization of Mycobacterium tuberculosis (Mtb). However, the mechanism of interaction between epithelial cells and Mtb is not well understood. In this study, we investigated the role of the heparin-binding hemagglutinin (HBHA) protein of Mtb in the function of epithelial cells. In particular, the autophagy of A549 cells was determined based on microtubule-associated protein 1 light chain 3 alpha (LC3) activity...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28223936/two-pore-channels-catalyzers-of-endolysosomal-transport-and-function
#19
REVIEW
Christian Grimm, Cheng-Chang Chen, Christian Wahl-Schott, Martin Biel
Two-pore channels (TPCs) have recently emerged as a novel class of non-selective cation channels in the endolysosomal system. There are two members in the human genome, TPC1 and TPC2. Studies with TPC knockout and knockdown models have revealed that these channels participate in the regulation of multiple endolysosomal trafficking pathways which when dysregulated can lead to or influence the development of a range of different diseases such as lysosomal storage, metabolic, or infectious diseases. TPCs have been demonstrated to be activated by different endogenous stimuli, PI(3,5)P2 and NAADP, and ATP has been found to block TPC activation via mTOR...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28223514/selective-autophagy-limits-cauliflower-mosaic-virus-infection-by-nbr1-mediated-targeting-of-viral-capsid-protein-and-particles
#20
Anders Hafrén, Jean-Luc Macia, Andrew J Love, Joel J Milner, Martin Drucker, Daniel Hofius
Autophagy plays a paramount role in mammalian antiviral immunity including direct targeting of viruses and their individual components, and many viruses have evolved measures to antagonize or even exploit autophagy mechanisms for the benefit of infection. In plants, however, the functions of autophagy in host immunity and viral pathogenesis are poorly understood. In this study, we have identified both anti- and proviral roles of autophagy in the compatible interaction of cauliflower mosaic virus (CaMV), a double-stranded DNA pararetrovirus, with the model plant Arabidopsis thaliana We show that the autophagy cargo receptor NEIGHBOR OF BRCA1 (NBR1) targets nonassembled and virus particle-forming capsid proteins to mediate their autophagy-dependent degradation, thereby restricting the establishment of CaMV infection...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
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