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https://www.readbyqxmd.com/read/29052596/t-6-11-renal-cell-carcinoma-a-study-of-seven-cases-including-two-with-aggressive-behavior-and-utility-of-cd68-pg-m1-in-the-differential-diagnosis-with-pure-epithelioid-pecoma-epithelioid-angiomyolipoma
#1
Anna Caliò, Matteo Brunelli, Diego Segala, Serena Pedron, Regina Tardanico, Andrea Remo, Stefano Gobbo, Emanuela Meneghelli, Claudio Doglioni, Ondrej Hes, Claudia Zampini, Pedram Argani, Guido Martignoni
Renal cell carcinomas with t(6;11) chromosome translocation involving the TFEB gene are indolent neoplasms which often occur in young patients. In this study, we report seven cases of renal cell carcinoma with TFEB rearrangement, two of whom had histologically proven metastasis. Patients (4F, 3M) ranged in age from 19 to 55 years (mean 37). One patient developed paratracheal and pleural metastases 24 months after surgery and died of disease after 46 months; another one recurred with neoplastic nodules in the perinephric fat and pelvic soft tissue...
October 20, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29046293/exercise-induces-tfeb-expression-and-activity-in-skeletal-muscle-in-a-pgc-1%C3%AE-dependent-manner
#2
Avigail T Erlich, Diane M Brownlee, Kaitlyn Beyfuss, David A Hood
The mitochondrial network in muscle is controlled by the opposing processes of mitochondrial biogenesis and mitophagy. The coactivator PGC-1α regulates biogenesis, while the transcription of mitophagy-related genes is controlled by transcription factor EB (TFEB). PGC-1α activation is induced with exercise, however the effect of exercise on TFEB is not fully known. We investigated the interplay between PGC-1α and TFEB on mitochondria in response to acute contractile activity in C2C12 myotubes, and following exercise in WT and PGC-1α KO mice...
October 18, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29036198/the-homeodomain-interacting-protein-kinase-hpk-1-preserves-protein-homeostasis-and-longevity-through-master-regulatory-control-of-the-hsf-1-chaperone-network-and-torc1-restricted-autophagy-in-caenorhabditis-elegans
#3
Ritika Das, Justine A Melo, Manjunatha Thondamal, Elizabeth A Morton, Adam B Cornwell, Beresford Crick, Joung Heon Kim, Elliot W Swartz, Todd Lamitina, Peter M Douglas, Andrew V Samuelson
An extensive proteostatic network comprised of molecular chaperones and protein clearance mechanisms functions collectively to preserve the integrity and resiliency of the proteome. The efficacy of this network deteriorates during aging, coinciding with many clinical manifestations, including protein aggregation diseases of the nervous system. A decline in proteostasis can be delayed through the activation of cytoprotective transcriptional responses, which are sensitive to environmental stress and internal metabolic and physiological cues...
October 16, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29035891/inhibiting-ros-tfeb-dependent-autophagy-enhances-salidroside-induced-apoptosis-in-human-chondrosarcoma-cells
#4
Wei Zeng, Tao Xiao, Anlie Cai, Weiliang Cai, Huanhuan Liu, Jingling Liu, Jie Li, Miduo Tan, Li Xie, Ying Liu, Xiangcheng Yang, Yi Long
BACKGROUND/AIMS: Autophagy modulation has been considered a potential therapeutic strategy for human chondrosarcoma, and a previous study indicated that salidroside exhibits significant anti-carcinogenic activity. However, the ability of salidroside to induce autophagy and its role in human chondrosarcoma cell death remains unclear. METHODS: We exposed SW1353 cells to different concentrations of salidroside (0.5, 1 and 2 mM) for 24 h. RT-PCR, Western-blotting, Immunocytofluorescence, and Luciferase Reporter Assays were used to evaluate whether salidroside activated the TFEB-dependent autophagy...
October 16, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29030472/erratum-for-salma-et-al-tfe3-and-tfeb-transcriptionally-regulate-peroxisome-proliferator-activated-receptor-%C3%AE-2-expression-in-adipocytes-and-mediate-adiponectin-and-glucose-levels-in-mice
#5
Nunciada Salma, Jun S Song, Akinori Kawakami, Suprabha P Devi, Mehdi Khaled, José M Cacicedo, David E Fisher
No abstract text is available yet for this article.
November 1, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/29025968/activation-of-ampk-mtorc1-mediated-autophagy-by-metformin-reverses-clk1-deficiency-sensitized-dopaminergic-neuronal-death
#6
Qiuting Yan, Chaojun Han, Guanghui Wang, John L Waddington, Longtai Zheng, Xuechu Zhen
The autophagy-lysosome pathway (ALP) plays a critical role in the pathology of Parkinson's disease (PD). Clk1 (coq7) is a mitochondrial hydroxylase that is essential for Coenzyme Q (ubiquinone) biosynthesis. We have reported previously that Clk1 regulates microglia activation via modulating microglia metabolic reprogramming, which contributes to dopaminergic neuronal survival. This study explored the direct effect of Clk1 on dopaminergic neuronal survival. We demonstrated that Clk1 deficiency inhibited dopaminergic neuronal autophagy in cultured MN9D dopaminergic neurons and in SNc of Clk+/- mutant mice and consequently sensitized dopaminergic neuron damage and behavioral defects...
October 12, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28993518/naringenin-ameliorates-acute-inflammation-by-regulating-intracellular-cytokine-degradation
#7
Lingtao Jin, Wenfeng Zeng, Fayun Zhang, Chunling Zhang, Wei Liang
Ungoverned activation of innate and adaptive immunity results in acute inflammatory disease, such as bacteria-induced endotoxemia and fulminant hepatitis by virus infection. Thus, therapeutic control of inflammation is crucial for clinical management of many human diseases. In murine models of LPS- and Con A-induced liver injury, we found that naringenin, a natural predominant flavanone, is capable of protecting against lethality induced by LPS and preventing inflammation-induced organ injury. The protective effect of naringenin is mediated by reducing the levels of several inflammatory cytokines...
October 9, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28993455/ehrlichia-activation-of-wnt-pi3k-mtor-signaling-inhibits-autolysosome-generation-and-autophagic-destruction-by-the-mononuclear-phagocyte
#8
Taslima T Lina, Tian Luo, Thangam-Sudha Velayutham, Seema Das, Jere W McBride
In multicellular organisms, autophagy is induced as an innate defense mechanism. Notably, the obligate intracellular bacterium, Ehrlichia chaffeensis, resides in early endosome-like vacuoles and circumvents lysosomal fusion through an unknown mechanism, thereby avoiding destruction in the autophagolysosome. In this study, we reveal that Wnt signaling plays a crucial role in inhibition of lysosomal fusion and autolysosomal destruction of ehrlichiae. During early infection, autophagosomes fuse with ehrlichial vacuoles to form an amphisome indicated by presence of autophagy markers such as LC3, Beclin-1 and p62...
October 9, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28993153/tfeb-activation-protects-against-cardiac-proteotoxicity-via-increasing-autophagic-flux
#9
Bo Pan, Hanming Zhang, Taixing Cui, Xuejun Wang
Insufficient lysosomal removal of autophagic cargoes in cardiomyocytes has been suggested as a main cause for the impairment of the autophagic-lysosomal pathway (ALP) in many forms of heart disease including cardiac proteinopathy and may play an important pathogenic role; however, the molecular basis and the correcting strategy for the cardiac ALP insufficiency require further investigation. The present study was sought to determine whether myocardial expression and activity of TFEB, the recently identified ALP master regulator, are impaired in a cardiac proteinopathy mouse model and to determine the effect of genetic manipulation of TFEB expression on autophagy and proteotoxicity in a cardiomyocyte model of proteinopathy...
October 7, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28987793/silver-nanoparticles-induce-lysosomal-autophagic-defects-and-decreased-expression-of-transcription-factor-eb-in-a549-human-lung-adenocarcinoma-cells
#10
Takamitsu Miyayama, Kota Fujiki, Masato Matsuoka
Although silver nanoparticles (AgNPs) are widely used in consumer and medical products, the mechanism by which AgNPs cause pulmonary damage is unclear. AgNPs are incorporated into cells and processed via the autophagy pathway. We examined the effects of AgNP exposure on autophagic flux and expression of transcription factor EB (TFEB) in A549 lung adenocarcinoma cells. In cells exposed to citrate-coated 60-nm AgNPs, confocal laser microscopic examination showed a decrease in the LysoTracker fluorescence signal and an increase in that of Cyto-ID, indicating lysosomal pH alkalization and autophagosome formation, respectively...
October 5, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28971552/tor-mediated-regulation-of-metabolism-in-aging
#11
REVIEW
Henri Antikainen, Monica Driscoll, Gal Haspel, Radek Dobrowolski
Cellular metabolism is regulated by the mTOR kinase, a key component of the molecular nutrient sensor pathway that plays a central role in cellular survival and aging. The mTOR pathway promotes protein and lipid synthesis and inhibits autophagy, a process known for its contribution to longevity in several model organisms. The nutrient-sensing pathway is regulated at the lysosomal membrane by a number of proteins for which deficiency triggers widespread aging phenotypes in tested animal models. In response to environmental cues, this recently discovered lysosomal nutrient-sensing complex regulates autophagy transcriptionally through conserved factors, such as the transcription factors TFEB and FOXO, associated with lifespan extension...
October 2, 2017: Aging Cell
https://www.readbyqxmd.com/read/28970837/lysosomal-ca-2-signaling-regulates-high-glucose-mediated-interleukin-1%C3%AE-secretion-via-transcription-factor-eb-in-human-monocytic-cells
#12
Hisa Hui Ling Tseng, Chi Teng Vong, Yiu Wa Kwan, Simon Ming-Yuen Lee, Maggie Pui Man Hoi
Aberrant activation of the innate immune system, including NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome-dependent interleukin-1β (IL-1β) secretion, has been implicated in the pathogenesis of type 2 diabetes mellitus (T2DM) and its complication. Our previous study demonstrated that hyperglycemia, a hallmark characteristic of T2DM, induced NLRP3 inflammasome-dependent caspase-1 activation and IL-1β maturation in human monocytic cells. In this study, we examined the underlying mechanisms of secreting IL-1β during hyperglycemia, with a focus on the alteration of Ca(2+) homeostasis and lysosomal exocytosis...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28970150/flcn-the-causative-gene-for-birt-hogg-dub%C3%A3-syndrome
#13
REVIEW
Laura S Schmidt, W Marston Linehan
Germline mutations in the novel tumor suppressor gene FLCN are responsible for the autosomal dominant inherited disorder Birt-Hogg-Dubé (BHD) syndrome that predisposes to fibrofolliculomas, lung cysts and spontaneous pneumothorax, and an increased risk for developing kidney tumors. Although the encoded protein, folliculin (FLCN), has no sequence homology to known functional domains, x-ray crystallographic studies have shown that the C-terminus of FLCN has structural similarity to DENN (differentially expressed in normal cells and neoplasia) domain proteins that act as guanine nucleotide exchange factors (GEFs) for small Rab GTPases...
September 29, 2017: Gene
https://www.readbyqxmd.com/read/28969862/melanotic-mit-family-translocation-neoplasms-expanding-the-clinical-and-molecular-spectrum-of-this-unique-entity-of-tumors
#14
Rola M Saleeb, John R Srigley, Joan Sweet, Cedric Doucet, Virginie Royal, Ying-Bei Chen, Fadi Brimo, Andrew Evans
MiT family translocation tumors are a group of neoplasms characterized by translocations involving MiT family transcription factors. The translocation renal cell carcinomas, TFE3 (Xp11.2) and TFEB (t6;11) are known members of this family. Melanotic Xp11 translocation renal cancer is a more recently described entity. To date only 14 cases have been described. It is characterized by a distinct set of features including a nested epithelioid morphology, melanin pigmentation, labeling for markers of melanocytic differentiation, lack of labeling for markers of renal tubular differentiation, predominance in a younger age population and association with aggressive clinical behavior...
August 25, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28945989/apolipoprotein-e4-inhibits-autophagy-gene-products-through-direct-specific-binding-to-clear-motifs
#15
Paul A Parcon, Meenakshisundaram Balasubramaniam, Srinivas Ayyadevara, Richard A Jones, Ling Liu, Robert J Shmookler Reis, Steven W Barger, Robert E Mrak, W Sue T Griffin
INTRODUCTION: Alzheimer apolipoprotein E (APOE) ε4,4 carriers have earlier disease onset and more protein aggregates than patients with other APOE genotypes. Autophagy opposes aggregation, and important autophagy genes are coordinately regulated by transcription factor EB (TFEB) binding to "coordinated lysosomal expression and regulation" (CLEAR) DNA motifs. METHODS: Autophagic gene expression was assessed in brains of controls and Alzheimer's disease (AD) patients parsed by APOE genotype and in a glioblastoma cell line expressing either ApoE3 or ApoE4...
September 22, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28933629/ezetimibe-ameliorates-steatohepatitis-via-amp-activated-protein-kinase-tfeb-mediated-activation-of-autophagy-and-nlrp3-inflammasome-inhibition
#16
Soo Hyun Kim, Gyuri Kim, Dai Hoon Han, Milim Lee, Irene Kim, Bohkyung Kim, Kook Hwan Kim, Young-Mi Song, Jeong Eun Yoo, Hye Jin Wang, Soo Han Bae, Yong-Ho Lee, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha, Myung-Shik Lee
Impairment in macroautophagy/autophagy flux and inflammasome activation are common characteristics of nonalcoholic steatohepatitis (NASH). Considering the lack of approved agents for treating NASH, drugs that can enhance autophagy and modulate inflammasome pathways may be beneficial. Here, we investigated the novel mechanism of ezetimibe, a widely prescribed drug for hypercholesterolemia, as a therapeutic option for ameliorating NASH. Human liver samples with steatosis and NASH were analyzed. For in vitro studies of autophagy and inflammasomes, primary mouse hepatocytes, human hepatoma cells, mouse embryonic fibroblasts with Ampk or Tsc2 knockout, and human or primary mouse macrophages were treated with ezetimibe and palmitate...
October 3, 2017: Autophagy
https://www.readbyqxmd.com/read/28891980/sinomenine-hydrochloride-inhibits-human-glioblastoma-cell-growth-through-reactive-oxygen-species-generation-and-autophagy-lysosome-pathway-activation-an-in-vitro-and-in-vivo-study
#17
Yumao Jiang, Yue Jiao, Zhiguo Wang, Tao Li, Yang Liu, Yujuan Li, Xiaoliang Zhao, Danqiao Wang
Glioblastoma is the most common malignant primary brain tumor, and it is one of the causes of cancer fatality in both adult and pediatric populations. Patients with glioblastoma require chemotherapy after surgical resection and radiotherapy. Therefore, chemotherapy constitutes a viable approach for the eradication of glioblastoma cells. In this study, the anti-tumor activity of sinomenine hydrochloride (SH) was evaluated in U87 and SF767 cells in vitro and in vivo. The results showed that SH potently inhibited U87 and SF767 cell viability and did not cause caspase-dependent cell death, as demonstrated by the absence of significant early apoptosis and caspase-3 cleavage...
September 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28890387/peptides-derived-from-transcription-factor-eb-bind-to-calcineurin-at-a-similar-region-as-the-nfat-type-motif
#18
Ruiwen Song, Jing Li, Jin Zhang, Lu Wang, Li Tong, Ping Wang, Huan Yang, Qun Wei, Huaibin Cai, Jing Luo
Calcineurin (CN) is involved in many physiological processes and interacts with multiple substrates. Most of the substrates contain similar motifs recognized by CN. Recent studies revealed a new CN substrate, transcription factor EB (TFEB), which is involved in autophagy. We showed that a 15-mer QSYLENPTSYHLQQS peptide from TFEB (TFEB-YLENP) bound to CN. When the TFEB-YLENP peptide was changed to YLAVP, its affinity for CN increased and it had stronger CN inhibitory activity. Molecular dynamics simulations revealed that the TFEB-YLENP peptide has the same docking sites in CN as the 15-mer DQYLAVPQHPYQWAK motif of the nuclear factor of activated T cells, cytoplasmic 1 (NFATc1-YLAVP)...
September 7, 2017: Biochimie
https://www.readbyqxmd.com/read/28861278/comparing-structural-and-transcriptional-drug-networks-reveals-signatures-of-drug-activity-and-toxicity-in-transcriptional-responses
#19
Francesco Sirci, Francesco Napolitano, Sandra Pisonero-Vaquero, Diego Carrella, Diego L Medina, Diego di Bernardo
We performed an integrated analysis of drug chemical structures and drug-induced transcriptional responses. We demonstrated that a network representing three-dimensional structural similarities among 5452 compounds can be used to automatically group together drugs with similar scaffolds, physicochemical parameters and mode-of-action. We compared the structural network to a network representing transcriptional similarities among a subset of 1309 drugs for which transcriptional response were available in the Connectivity Map data set...
2017: NPJ Systems Biology and Applications
https://www.readbyqxmd.com/read/28851811/the-mitf-tfe-family-of-transcription-factors-master-regulators-of-organelle-signaling-metabolism-and-stress-adaptation
#20
Logan Slade, Thomas Pulinilkunnil
The microphthalmia family (MITF, TFEB, TFE3, and TFEC) of transcription factors are emerging global regulators of cancer cell survival and energy metabolism, both through the promotion of lysosomal genes as well as newly characterized targets such as oxidative metabolism and the oxidative stress response. Additionally, MiT/TFE factors can regulate lysosomal signaling which includes the mTORC1 and Wnt/β-Catenin pathways, which are both substantial contributors to oncogenic signaling. This review describes recent discoveries in MiT/TFE research and how they impact multiple cancer subtypes...
August 29, 2017: Molecular Cancer Research: MCR
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