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https://www.readbyqxmd.com/read/29444517/acetyl-coa-synthetase-2-promotes-cell-migration-and-invasion-of-renal-cell-carcinoma-by-upregulating-lysosomal-associated-membrane-protein-1-expression
#1
Lv Yao, Xiaoqiang Guo, Yaoting Gui
BACKGROUND/AIMS: Reprogramming energy metabolism is an emerging hallmark of many cancers, and this alteration is especially evident in renal cell carcinomas (RCCs). However, few studies have been conducted on lipid metabolism. This study investigated the function and mechanism of lipid metabolism-related acetyl-CoA synthetase 2 (ACSS2) in RCC development, cell migration and invasion. METHODS: Quantitative real-time PCR (qRT-PCR) was used to determine the expression of ACSS2 in cancer tissue and adjacent tissue...
2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29378795/small-gtpase-immunity-associated-proteins-mediate-resistance-to-toxoplasma-gondii-infection-in-lewis-rat
#2
Chi Yong Kim, Xuejin Zhang, William H Witola
Rats vary in their susceptibilities to Toxoplasma gondii infection depending on the rat strain. Compared to the T. gondii-susceptible Brown Norway (BN) rat, the Lewis (LEW) rat is extremely resistant to T. gondii Thus, these two rat strains are ideal models for elucidating host mechanisms that are important for host resistance to T. gondii infection. Therefore, in our efforts to unravel molecular factors directing the protective early innate immune response in the LEW rat, we performed RNA sequencing analysis of the LEW versus BN rat, with or without T...
January 29, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29367744/overexpression-of-parkin-protects-retinal-ganglion-cells-in-experimental-glaucoma
#3
Yi Dai, Xinxin Hu, Xinghuai Sun
Glaucoma is a leading cause of irreversible blindness and characterized by progressive damage of retinal ganglion cells (RGCs). Growing evidences have linked impaired mitophagy with neurodegenerative diseases, while the E3 ubiquitin ligase parkin may play a key role. However, the pathophysiological relationship between parkin and glaucoma remains largely unknown. Using chronic hypertensive glaucoma rats induced by translimbal laser photocoagulation, we show here that the protein level of parkin and its downstream optineurin proteins were increased in hypertensive retinas...
January 24, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29367433/n-glycome-of-the-lysosomal-glycocalyx-is-altered-in-niemann-pick-type-c-disease-model-cells
#4
Marko Kosicek, Ivan Gudelj, Anita Horvatic, Tanja Jovic, Frano Vuckovic, Gordan Lauc, Silva Hecimovic
Increasing evidence implicates lysosomal dysfunction in the pathogenesis of neurodegenerative diseases, including the rare inherited lysosomal storage disorders (LSDs) and the most common neurodegenerative diseases, such as Alzheimer's and Parkinson's disease (AD and PD). While the triggers of the lysosomal impairment may involve the accumulated macromolecules or dysfunction of the lysosomal enzymes, the role of the lysosomal glycocalyx in the lysosomal (dys)function has not been studied. The goal of this work was to analyze whether there are changes in the lysosomal glycocalyx in a cellular model of a LSD Niemann-Pick type C disease (NPC)...
January 24, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29348412/influence-of-autophagy-on-acute-kidney-injury-in-a-murine-cecal-ligation-and-puncture-sepsis-model
#5
Satoshi Sunahara, Eizo Watanabe, Masahiko Hatano, Paul E Swanson, Takehiko Oami, Lisa Fujimura, Youichi Teratake, Takashi Shimazui, Chiwei Lee, Shigeto Oda
The role of autophagy in the maintenance of renal homeostasis during sepsis is not well understood. We therefore aimed to determine the influence of autophagy on kidney during sepsis using a murine sepsis model, i.e. cecal ligation and puncture (CLP). In CLP treated animals, the number of autolysosomes observed by electron microscopy increased over time. The number of autophagosomes in CLP animals decreased relative sham operated controls at 24 hrs after CLP, indicating that autophagy flux is already diminishing by that time...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29307823/autophagy-mediated-upregulation-of-cytoplasmic-claudin-1-stimulates-the-degradation-of-sqstm1-p62-under-starvation
#6
Jaewhan Kim, Sunkyung Choi, Jong Ok Kim, Kee K Kim
Claudin 1, a major tight junction protein, is highly expressed in various types of tumors such as thyroid, breast, and colorectal cancers. Moreover, claudin 1 is frequently found in the cytoplasm in various types of tumor cells. However, the cytoplasmic function of claudin 1 in tumors still remains largely unknown. Here, we investigated the novel function of cytoplasmic claudin 1 in autophagy. The mRNA expression level of claudin 1 was higher in several types of tumors than in normal tissues. Furthermore, colon tumor tissues showed increased autophagy compared with the adjacent normal tissues...
January 4, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29306553/knockout-of-autophagy-gene-atg5-in-mice-vaginal-cells-abrogates-cytokine-response-and-pathogen-clearance-during-vaginal-infection-of-candida-albicans
#7
Ankit Shroff, Roicy Sequeira, Vainav Patel, K V R Reddy
The female reproductive tract (FRT) presents a unique challenge to the mucosal immune system as it needs to monitor constantly for the presence of opportunistic pathogens amidst its commensal flora. During infection, autophagy plays a critical role in pathogen clearance, presentation of antigens and production of pro-inflammatory cytokines. However, no information is available that describes the role of autophagy in mouse vaginal infection of Candida albicans. The objective of our study is to evaluate the effect of autophagy gene, ATG5 knockout in vaginal cells in response to vaginal C...
December 28, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/29295909/lamp1-increases-the-efficiency-of-lassa-virus-infection-by-promoting-fusion-in-less-acidic-endosomal-compartments
#8
Christine E Hulseberg, Lucie Fénéant, Katarzyna M Szymańska, Judith M White
Lassa virus (LASV) is an arenavirus whose entry into host cells is mediated by a glycoprotein complex (GPC) comprised of a receptor binding subunit, GP1, a fusogenic transmembrane subunit, GP2, and a stable signal peptide. After receptor-mediated internalization, arenaviruses converge in the endocytic pathway, where they are thought to undergo low-pH-triggered, GPC-mediated fusion with a late endosome membrane. A unique feature of LASV entry is a pH-dependent switch from a primary cell surface receptor (α-dystroglycan) to an endosomal receptor, lysosomal-associated membrane protein (Lamp1)...
January 2, 2018: MBio
https://www.readbyqxmd.com/read/29286619/comparison-of-diagnostic-yield-of-a-fish-panel-against-conventional-cytogenetic-studies-for-hematological-malignancies-a-south-indian-referral-laboratory-analysis-of-201-cases
#9
Vishal Ashok, Ramya Ranganathan, Smitha Chander, Sharat Damodar, Sunil Bhat, Nataraj K S, Satish Kumar A, Sachin Suresh Jadav, Mahesh Rajashekaraiah, Sundareshan T S
Objectives: Genetic markers are crucial fort diagnostic and prognostic investigation of hematological malignancies (HM). The conventional cytogenetic study (CCS) has been the gold standard for more than five decades. However, FISH (Fluorescence in Situ Hybridization) testing has become a popular modality owing to its targeted approach and the ability to detect abnormalities in non-mitotic cells. We here aimed to compare the diagnostic yields of a FISH panel against CCS in HMs. Methods: Samples of bone marrow and peripheral blood for a total of 201 HMs were tested for specific gene rearrangements using multi-target FISH and the results were compared with those from CCS...
December 29, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/29277005/landmarks-of-endosomal-remodeling-in-the-early-phase-of-cytomegalovirus-infection
#10
Ljerka Karleuša, Hana Mahmutefendić, Maja Ilić Tomaš, Gordana Blagojević Zagorac, Pero Lučin
Cytomegaloviruses (CMVs) extensively rearrange the cellular membrane system to develop assembly compartment (AC), but the earliest events in this process are poorly characterized. Here, we demonstrate that murine CMV (MCMV) infection restrains endosomal trafficking of cargo molecules that travel along the recycling (TfR and MHC-I) and the late endosomal (EGFR, M6PR, Lamp1) circuit. Internalized cargo accumulates in Arf6-, Rab5-, Rab22A-, and Rab11-positive and Rab35-, Rab8-, and Rab10-negative juxtanuclear endosomes, suggesting the disruption of Arf/Rab regulatory cascade at the stage of sorting endosomes and the endosomal recycling compartment...
December 22, 2017: Virology
https://www.readbyqxmd.com/read/29274721/cpg-odn-exerts-a-neuroprotective-effect-via-the-tlr9-pampk-signaling-pathway-by-activation-of-autophagy-in-a-neonatal-hie-rat-model
#11
Lan Ye, Zhanhui Feng, Desislava Doycheva, Jay Malaguit, Brandon Dixon, Ningbo Xu, John H Zhang, Jiping Tang
Hypoxic Ischemic Encephalopathy (HIE) is an injury caused to the brain due to prolonged lack of oxygen and blood supply which results in death or long-term disabilities. The main aim of this study was to investigate the role of Cytosine-phospho-guanine oligodeoxynucleotide (CpG-ODN) in autophagy after HIE. Ten-day old (P10) rat pups underwent right common carotid artery ligation followed by 2.5h of hypoxia as previously described by Rice-Vannucci. At 1h post HIE, rats were intranasally administered with recombinant CpG-ODN...
December 21, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/29274360/disulfiram-with-or-without-metformin-inhibits-oesophageal-squamous-cell-carcinoma-in%C3%A2-vivo
#12
Rupal Jivan, Jade Peres, Leonard Howard Damelin, Reubina Wadee, Robin Bruce Veale, Sharon Prince, Demetra Mavri-Damelin
Oesophageal squamous cell carcinoma (OSCC) is highly prevalent in developing countries but there has been little recent progress into efficacious yet affordable treatment strategies. Drug repurposing is one attractive approach for cancer therapy. Disulfiram (DSF), used to treat alcoholism, inhibits cancer growth and we previously found that DSF perturbs protein degradation/turnover pathways in vitro. This was enhanced by combining DSF with the anti-diabetic drug metformin (Met). Here, we investigated DSF with/without Met, against OSCC in vivo...
March 28, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29273568/hantavirus-gc-induces-long-term-immune-protection-via-lamp-targeting-dna-vaccine-strategy
#13
Dong-Bo Jiang, Jin-Peng Zhang, Lin-Feng Cheng, Guan-Wen Zhang, Yun Li, Zi-Chao Li, Zhen-Hua Lu, Zi-Xin Zhang, Yu-Chen Lu, Lian-He Zheng, Fang-Lin Zhang, Kun Yang
Hemorrhagic fever with renal syndrome (HFRS) occurs widely throughout Eurasia. Unfortunately, there is no effective treatment, and prophylaxis remains the best option against the major pathogenic agent, hantaan virus (HTNV), which is an Old World hantavirus. However, the absence of cellular immune responses and immunological memory hampers acceptance of the current inactivated HFRS vaccine. Previous studies revealed that a lysosome-associated membrane protein 1 (LAMP1)-targeting strategy involving a DNA vaccine based on the HTNV glycoprotein Gn successfully conferred long-term immunity, and indicated that further research on Gc, another HTNV antigen, was warranted...
December 19, 2017: Antiviral Research
https://www.readbyqxmd.com/read/29258566/5-fu-resistant-emt-like-pancreatic-cancer-cells-are-hypersensitive-to-photochemical-internalization-of-the-novel-endoglin-targeting-immunotoxin-cd105-saporin
#14
Kaja Lund, Cathrine Elisabeth Olsen, Judith Jing Wen Wong, Petter Angell Olsen, Nina Therese Solberg, Anders Høgset, Stefan Krauss, Pål Kristian Selbo
BACKGROUND: Development of resistance to 5-fluorouracil (5-FU) is a major problem in treatment of various cancers including pancreatic cancer. In this study, we reveal important resistance mechanisms and photochemical strategies to overcome 5-FU resistance in pancreatic adenocarcinoma. METHODS: 5-FU resistant (5-FUR), epithelial-to-mesenchymal-like sub-clones of the wild type pancreatic cancer cell line Panc03.27 were previously generated in our lab. We investigated the cytotoxic effect of the endosomal/lysosomal-localizing photosensitizer TPCS2a (fimaporfin) combined with light (photochemical treatment, PCT) using MTS viability assay, and used fluorescence microscopy to show localization of TPCS2a and to investigate the effect of photodamage of lysosomes...
December 19, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29246495/elevated-peripheral-myelin-protein-22-reduced-mitotic-potential-and-proteasome-impairment-in-dermal-fibroblasts-from-charcot-marie-tooth-disease-type-1a-patients
#15
Sooyeon Lee, Hannah Bazick, Vinita Chittoor-Vinod, Mohammed Omar Al Salihi, Guangbin Xia, Lucia Notterpek
A common form of hereditary autosomal dominant demyelinating neuropathy known as Charcot-Marie-Tooth disease type 1A (CMT1A) is linked with duplication of the peripheral myelin protein 22 (PMP22) gene. Although studies from animal models have led to better understanding of the pathobiology of these neuropathies, there continues to be a gap in the translation of findings from rodents to humans. As PMP22 was originally identified in fibroblasts as growth arrest specific gene 3 (gas3) and is expressed broadly in the body, it was tested whether skin cells from neuropathic patients would display the cellular pathology observed in Schwann cells from rodent models...
December 12, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/29237927/distinct-rab7-related-endosomal-autophagic-lysosomal-dysregulation-observed-in-cortex-and-hippocampus-in-appswe-psen1de9-mouse-model-of-alzheimer-s-disease
#16
Li Ba, Xiao-Hua Chen, Yan-Lin Chen, Qing Nie, Zhi-Jun Li, Feng-Fei Ding, Min Zhang
BACKGROUND: Amyloid-β deposition and accumulation of autophagic vacuoles are pathologic features of Alzheimer's disease (AD). Dysregulation of the endosomal-autophagic-lysosomal (EAL) pathway, which impairs amyloid precursor protein processing, is one of the earliest changes in AD. However, the precise role of EAL pathway in neurodegeneration remains unclear. This study aimed to investigate the role of EAL pathway in AD and further study the mechanism of EAL dysfunction. METHODS: We used 3-, 7-, and 12-month-old APPswe/PSEN1dE9 (APP/PS1) mice to model different stages of AD with age- and gender-matched wild-type littermates as controls (4-7 mice per group) and detected the changes of EAL markers, endosomal organizers Rab5 and Rab7, autophagosome marker LC3B, and lysosomal proteins Lamp1/2 in cortex and hippocampus by immunohistochemistry and Western blotting analysis...
December 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/29227302/the-target-invites-a-foe-antibody-drug-conjugates-in-gynecologic-oncology
#17
Maira P Campos, Gottfried E Konecny
PURPOSE OF REVIEW: Antibody-drug conjugates (ADCs) represent a promising new class of cancer therapeutics. Currently more than 60 ADCs are in clinical development, however, only very few trials focus on gynecologic malignancies. In this review, we summarize the most recent advances in ADC drug development with an emphasis on how this progress relates to patients diagnosed with gynecologic malignancies and breast cancer. RECENT FINDINGS: The cytotoxic payloads of the majority of the ADCs that are currently in clinical trials for gynecologic malignancies or breast cancer are auristatins (MMAE, MMAF), maytansinoids (DM1, DM4), calicheamicin, pyrrolobenzodiazepines and SN-38...
December 8, 2017: Current Opinion in Obstetrics & Gynecology
https://www.readbyqxmd.com/read/29209172/the-role-of-netrin-1-in-improving-functional-recovery-through-autophagy-stimulation-following-spinal-cord-injury-in-rats
#18
Liangjie Bai, Xifan Mei, Yanfeng Wang, Yajiang Yuan, Yunlong Bi, Gang Li, Hongyu Wang, Peng Yan, Gang Lv
Our previous findings indicated that treatment with Netrin-1 could improve functional recovery through the stimulation of autophagy, by activating the AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) signaling pathway in rats following spinal cord injury (SCI). However, the underlying mechanisms were not elucidated. The purpose of this study was to investigate the underlying mechanisms by which Netrin-1 promotes autophagy and improves functional recovery after SCI. Following controlled SCI in Sprague-Dawley rats, we observed that the autophagic flux in neurons was impaired, as reflected by the accumulation of light chain 3-II (LC3-II)-positive and LC3-positive autophagosomes (APs), accompanied by the accumulation of the autophagic substrate, Sequestosome 1 (SQSTM1; also known as p62)...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29170033/6-hydroxydopamine-induces-autophagic-flux-dysfunction-by-impairing-transcription-factor-eb-activation-and-lysosomal-function-in-dopaminergic-neurons-and-sh-sy5y-cells
#19
Xin He, Wei Yuan, Zijian Li, Yang Hou, Liu Fei, Juan Feng
Autophagy deregulation has been implicated in Parkinson's disease (PD), yet the role of autophagy in neuronal survival remains controversial. In this study, we comprehensively investigated the time-course of autophagy-related markers in 6-OHDA-induced Parkinsonian rat models and assessed its effect on the state of autophagic flux both in vivo and in vitro. We observed an early activation of autophagy followed by autophagic flux impairment, which was confirmed with autophagy inhibitor chloroquine in vivo and Ad-GFP-mCherry-LC3-infected SH-SY5Y cells in vitro...
November 20, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29158485/cytoplasmic-cleavage-of-dppa3-is-required-for-intracellular-trafficking-and-cleavage-stage-development-in-mice
#20
Seung-Wook Shin, Edgar John Vogt, Maria Jimenez-Movilla, Boris Baibakov, Jurrien Dean
Degradation of maternal proteins by the ubiquitin-proteasome system (UPS) accompanies the maternal-to-zygotic transition. DPPA3/Stella/PGC7, encoded by a maternal effect gene, is present in the nucleus and cytoplasm of zygotes and has been associated with protecting the female pronucleus from TET3-mediated demethylation. We now report that cytoplasmic DPPA3 is partially cleaved by the ubiquitin-proteasome system and an N-terminus fragment remains in the cytoplasm where it associates with early and re-cycling endosomes...
November 21, 2017: Nature Communications
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