Read by QxMD icon Read


Longhua Liu, Zhipeng Tao, Louise D Zheng, Joseph P Brooke, Cayleen M Smith, Dongmin Liu, Yun Chau Long, Zhiyong Cheng
Mitochondrial uncoupling proteins (UCPs) are inducible and play an important role in metabolic and redox homeostasis. Recent studies have suggested that FoxO1 controls mitochondrial biogenesis and morphology, but it remains largely unknown how FoxO1 may regulate mitochondrial UCPs. Here we show that FoxO1 interacted with transcription factor EB (Tfeb), a key regulator of autophagosome and lysosome, and mediated the expression of UCP1, UCP2 and UCP3 differentially via autophagy in adipocytes. UCP1 was down-regulated but UCP2 and UCP3 were upregulated during adipocyte differentiation, which was associated with increased Tfeb and autophagy activity...
2016: Cell Death Discovery
Santosh Chauhan, Suresh Kumar, Ashish Jain, Marisa Ponpuak, Michal H Mudd, Tomonori Kimura, Seong Won Choi, Ryan Peters, Michael Mandell, Jack-Ansgar Bruun, Terje Johansen, Vojo Deretic
Selective autophagy performs an array of tasks to maintain intracellular homeostasis, sterility, and organellar and cellular functionality. The fidelity of these processes depends on precise target recognition and limited activation of the autophagy apparatus in a localized fashion. Here we describe cooperation in such processes between the TRIM family and Galectin family of proteins. TRIMs, which are E3 ubiquitin ligases, displayed propensity to associate with Galectins. One specific TRIM, TRIM16, interacted with Galectin-3 in a ULK1-dependent manner...
October 10, 2016: Developmental Cell
Petr Vodicka, Kathryn Chase, Maria Iuliano, Adelaide Tousley, Dana T Valentine, Ellen Sapp, Kimberly B Kegel-Gleason, Miguel Sena-Esteves, Neil Aronin, Marian DiFiglia
BACKGROUND: Mutant huntingtin (mHTT) is encoded by the Huntington's disease (HD) gene and its accumulation in the brain contributes to HD pathogenesis. Reducing mHTT levels through activation of the autophagosome-lysosomal pathway may have therapeutic benefit. Transcription factor EB (TFEB) regulates lysosome biogenesis and autophagy. OBJECTIVE: To examine if increasing TFEB protein levels in HD mouse striatum induces autophagy and influences mHTT levels. METHODS: We introduced cDNA encoding TFEB with an HA tag (TFEB-HA) under the control of neuron specific synapsin 1 promoter into the striatum of 3 month old HDQ175/Q7 mice using adeno-associated virus AAV2/9...
October 1, 2016: Journal of Huntington's Disease
Jianbin Zhang, Jigang Wang, Jian Xu, Yuanqiang Lu, Jiukun Jiang, Liming Wang, Han-Ming Shen, Dajing Xia
Curcumin is a hydrophobic polyphenol derived from the herb Curcumalonga and its wide spectrum of pharmacological activities has been widely studied. It has been reported that Curcumin can induce autophagy through inhibition of the Akt-mTOR pathway. However, the effect of Curcumin on lysosome remains largely elusive. In this study, we first found that Curcumin treatment enhances autophagic flux in both human colon cancer HCT116 cells and mouse embryonic fibroblasts (MEFs). Moreover, Curcumin treatment promotes lysosomal function, evidenced by the increased lysosomal acidification and enzyme activity...
September 28, 2016: Oncotarget
Paul Saftig, Albert Haas
Lysosomes are digestive organelles of the endocytic and autophagic pathways. Increasing lysosome enzyme activities could help to clear pathological cellular waste. A recent study shows that lysosomal digestive functions can be promoted in isolated cells and mice by pharmacologically stimulating the autophagy- and lysosome-regulating transcription factors TFEB and ZKSCAN3 through previously unrecognized mTORC1-independent pathways acting via PKC.
September 28, 2016: Nature Cell Biology
William J Smiles, Evelyn B Parr, Vernon G Coffey, Orly Lacham-Kaplan, John A Hawley, Donny M Camera
Alcohol ingestion decreases post-exercise rates of muscle protein synthesis, but the mechanism(s) (e.g., increased protein breakdown) underlying this observation are unknown. Autophagy is an intracellular "recycling" system required for homeostatic substrate and organelle turnover; its dysregulation may provoke apoptosis and lead to muscle atrophy. We investigated the acute effects of alcohol ingestion on autophagic cell signaling responses to a bout of concurrent (combined resistance- and endurance-based) exercise...
September 27, 2016: American Journal of Physiology. Endocrinology and Metabolism
Alessia Calcagnì, Lotte Kors, Eric Verschuren, Rossella De Cegli, Nicolina Zampelli, Edoardo Nusco, Stefano Confalonieri, Giovanni Bertalot, Salvatore Pece, Carmine Settembre, Gabriel G Malouf, Jaklien C Leemans, Emile de Heer, Marco Salvatore, Dorien Jm Peters, Pier Paolo Di Fiore, Andrea Ballabio
TFE-fusion renal cell carcinomas (TFE-fusion RCCs) are caused by chromosomal translocations that lead to overexpression of the TFEB and TFE3 genes (Kauffman et al., 2014). The mechanisms leading to kidney tumor development remain uncharacterized and effective therapies are yet to be identified. Hence, the need to model these diseases in an experimental animal system (Kauffman et al., 2014). Here, we show that kidney-specific TFEB overexpression in transgenic mice, resulted in renal clear cells, multi-layered basement membranes, severe cystic pathology, and ultimately papillary carcinomas with hepatic metastases...
2016: ELife
Jason J Kwon, Jeffrey A Willy, Kayla A Quirin, Ronald C Wek, Murray Korc, Xiao-Ming Yin, Janaiah Kota
Pancreatic Ductal Adenocarcinoma (PDAC) is a highly lethal malignancy that responds poorly to current therapeutic modalities. In an effort to develop novel therapeutic strategies, we found downregulation of miR-29 in pancreatic cancer cells, and overexpression of miR-29a sensitized chemotherapeutic resistant pancreatic cancer cells to gemcitabine, reduced cancer cell viability, and increased cytotoxicity. Furthermore, miR-29a blocked autophagy flux, as evidenced by an accumulation of autophagosomes and autophagy markers, LC3B and p62, and a decrease in autophagosome-lysosome fusion...
September 10, 2016: Oncotarget
Purvi C Trivedi, Jordan J Bartlett, Lester J Perez, Keith R Brunt, Jean Francois Legare, Ansar Hassan, Petra C Kienesberger, Thomas Pulinilkunnil
Impaired cardiac metabolism in the obese and diabetic heart leads to glucolipotoxicity and ensuing cardiomyopathy. Glucolipotoxicity causes cardiomyocyte injury by increasing energy insufficiency, impairing proteasomal-mediated protein degradation and inducing apoptosis. Proteasome-evading proteins are degraded by autophagy in the lysosome, whose metabolism and function are regulated by master regulator transcription factor EB (TFEB). Limited studies have examined the impact of glucolipotoxicity on intra-lysosomal signaling proteins and their regulators...
September 9, 2016: Biochimica et Biophysica Acta
Yang Li, Meng Xu, Xiao Ding, Chen Yan, Zhiqin Song, Lianwan Chen, Xiahe Huang, Xin Wang, Youli Jian, Guihua Tang, Changyong Tang, Yingtong Di, Shuzhen Mu, Xuezhao Liu, Kai Liu, Ting Li, Yingchun Wang, Long Miao, Weixiang Guo, Xiaojiang Hao, Chonglin Yang
Lysosomes respond to environmental cues by controlling their own biogenesis, but the underlying mechanisms are poorly understood. Here we describe a protein kinase C (PKC)-dependent and mTORC1-independent mechanism for regulating lysosome biogenesis, which provides insights into previously reported effects of PKC on lysosomes. By identifying lysosome-inducing compounds we show that PKC couples activation of the TFEB transcription factor with inactivation of the ZKSCAN3 transcriptional repressor through two parallel signalling cascades...
October 2016: Nature Cell Biology
Jun Lin, Shan-Shan Shi, Ji-Qian Zhang, Yun-Jiao Zhang, Li Zhang, Yun Liu, Pei-Pei Jin, Peng-Fei Wei, Rong-Hua Shi, Wei Zhou, Long-Ping Wen
Many nanomaterials are reported to disrupt lysosomal function and homeostasis, but how cells sense and then respond to nanomaterial-elicited lysosome stress is poorly understood. Nucleus translocation of transcription factor EB (TFEB) plays critical roles in lysosome biogenesis following lysosome stress induced by starvation. The authors previously reported massive cellular vacuolization, along with autophagy induction, in cells treated with rare earth oxide (REO) nanoparticles. Here, the authors identify these giant cellular vacuoles as abnormally enlarged and alkalinized endo/lysosomes whose formation is dependent on macropinocytosis...
September 4, 2016: Small
Owen A Brady, Heba I Diab, Rosa Puertollano
The Rags represent a unique family of evolutionarily conserved, heterodimeric, lysosome-localized small GTPases that play an indispensible role in regulating cellular metabolism in response to various amino acid signaling mechanisms. Rapid progress in the field has begun to unveil a picture in which Rags act as central players in translating information regarding cellular amino acid levels by modulating their nucleotide binding status through an ensemble of support proteins localized in and around the lysosomes...
August 31, 2016: Small GTPases
Ji-Young Choi, Sangmee Ahn Jo
Intercellular adhesion molecule1 (ICAM1) is involved in adhesion and transmigration of leukocytes across endothelium, promoting brain inflammation and leading to brain diseases. Here, we studied the mechanism that regulates ICAM expression in response to proinflammatory cytokine tumor necrosis factor alpha (TNF-α). ICAM1 mRNA and protein levels in human brain microvascular endothelial cells dramatically increased after TNF-α treatment. TNF-α also upregulated histone demethylases KDM1B and KDM7A responsible for demethylation of H3K9me2, a well-known repression marker...
September 23, 2016: Biochemical and Biophysical Research Communications
Pedram Argani, Victor E Reuter, Lei Zhang, Yun-Shao Sung, Yi Ning, Jonathan I Epstein, George J Netto, Cristina R Antonescu
Renal cell carcinomas (RCCs) with the t(6;11)(p21;q12) chromosome translocation are low-grade RCC which often occur in young patients. They typically feature an unusual biphasic morphology characterized by nests of larger epithelioid cells surrounding intraluminal collections of smaller cells clustered around basement membrane material. The t(6;11)(p21;q12) translocation fuses the Alpha (MALAT1) gene with the TFEB transcription factor gene, resulting in upregulated expression of intact native TFEB that drives the aberrant expression of melanocytic markers which is a hallmark of this distinctive neoplasm...
November 2016: American Journal of Surgical Pathology
Matteo Brunelli, Francesco Erdini, Luca Cima, Albino Eccher, Adele Fioravanzo, Stefano Gobbo, Diego Segala, Claudio Ghimenton, Guido Mazzoleni, Enrico Munari, Rodolfo Carella, Guido Martignoni
Little is known about the aminopeptidase CD13 in renal neoplasia according to the new 2016 World Health Organization renal tumor classification. We selected 175 cases, including 79 clear cell, 31 papillary, 24 chromophobe, 8 clear cell papillary renal cell carcinomas (RCCs), 21 oncoytomas, and 12 microphthalmia transcription factor family translocation RCCs: 4 t(6;11)/transcription factor EB (TFEB), 7 t(Xp11) with 2 cystic variants and 1 t(X;17). GATA binding protein 3 (GATA-3) was inserted as control. Expression of proximal antigen CD13 was observed in 63/79 (80%) clear cell, 25/31 (81%) papillary, 3/8 (37%) clear cell papillary, 1/4 (25%) t(6;11)/TFEB, 2/7 (28%) cystic t(Xp11), and in 1/1 t(X;17) RCCs...
August 23, 2016: Applied Immunohistochemistry & Molecular Morphology: AIMM
Yohei Sato, Hiroshi Kobayashi, Takashi Higuchi, Yohta Shimada, Hiroyuki Ida, Toya Ohashi
Pompe disease (PD) is a lysosomal disorder caused by acid α-glucosidase (GAA) deficiency. Progressive muscular weakness is the major symptom of PD, and enzyme replacement therapy can improve the clinical outcome. However, to achieve a better clinical outcome, alternative therapeutic strategies are being investigated, including gene therapy and pharmacological chaperones. We previously used lentiviral vector-mediated GAA gene transfer in PD patient-specific induced pluripotent stem cells. Some therapeutic efficacy was observed, although glycogen accumulation was not normalized...
2016: Molecular Therapy. Methods & Clinical Development
Zahida Khan, Shinichiro Yokota, Yoshihiro Ono, Aaron W Bell, Michael Oertel, Donna B Stolz, George K Michalopoulos
BACKGROUND: Alpha-1 antitrypsin deficiency (A1ATD) can progress to cirrhosis and hepatocellular carcinoma; however, not all patients are susceptible to severe liver disease. In A1ATD, a toxic gain-of-function mutation generates insoluble ATZ "globules" in hepatocytes, overwhelming protein clearance mechanisms. The relationship between bile acids and hepatocytic autophagy is less clear, but may involve altered gene expression pathways. Based on previous findings that bile duct ligation (BDL) induces autophagy, we hypothesized that retained bile acids may have hepatoprotective effects in PiZZ transgenic mice, which model A1ATD...
August 18, 2016: Gene Expression
Jordan J Bartlett, Purvi C Trivedi, Pollen Yeung, Petra C Kienesberger, Thomas Pulinilkunnil
Doxorubicin (DOX) is an effective anti-cancer agent. However, DOX treatment increases patient susceptibility to dilated cardiomyopathy. DOX predisposes cardiomyocytes to insult by suppressing mitochondrial energy metabolism, altering calcium flux, and disrupting proteolysis and proteostasis. Prior studies have assessed the role of macroautophagy in DOX cardiotoxicity; however, limited studies have examined whether DOX mediates cardiac injury through dysfunctions in inter- and/or intra-lysosomal signaling events...
August 3, 2016: Biochemical Journal
Hi-Jai R Shin, Hyunkyung Kim, Keun Il Kim, Sung Hee Baek
Macroautophagy (hereafter referred to as autophagy) is an essential self-digestion process to maintain homeostasis and promote survival in response to starvation. Although the components of autophagy in the cytoplasm have been well-studied, little has been known about the fine-tuning mechanism of autophagy through epigenetic regulations. Recently, we identified the histone arginine methyltransferase CARM1 as a new component and followed histone H3R17 dimethylation as a critical epigenetic mark in starvation-induced autophagy...
August 3, 2016: Autophagy
Matthew Gruner, Jeremy Grubbs, Aja McDonagh, Dominic Valdes, Ari Winbush, Alexander M van der Linden
Food and feeding-state dependent changes in chemoreceptor gene expression may allow Caenorhabditis elegans to modify their chemosensory behavior, but the mechanisms essential for these expression changes remain poorly characterized. We had previously shown that expression of a feeding state-dependent chemoreceptor gene, srh-234, in the ADL sensory neuron of C. elegans is regulated via the MEF-2 transcription factor. Here, we show that MEF-2 acts together with basic helix-loop-helix (bHLH) transcription factors to regulate srh-234 expression as a function of feeding state...
August 2016: PLoS Genetics
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"