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https://www.readbyqxmd.com/read/28213823/long-term-resistance-exercise-induced-muscular-hypertrophy-is-associated-with-autophagy-modulation-in-rats
#1
Insu Kwon, Yongchul Jang, Joon-Yong Cho, Young C Jang, Youngil Lee
Elevation of anabolism and concurrent suppression of catabolism are critical metabolic adaptations for muscular hypertrophy in response to resistance exercise (RE). Here, we investigated if RE-induced muscular hypertrophy is acquired by modulating a critical catabolic process autophagy. Male Wistar Hannover rats (14 weeks old) were randomly assigned to either sedentary control (SC, n = 10) or resistance exercise (RE, n = 10). RE elicited significant hypertrophy of flexor digitorum profundus (FDP) muscles in parallel with enhancement in anabolic signaling pathways (phosphorylation of AKT, mTOR, and p70S6K)...
February 17, 2017: Journal of Physiological Sciences: JPS
https://www.readbyqxmd.com/read/28195531/-strong-strong-multiplex-image-based-autophagy-rnai-screening-identifies-smcr8-as-ulk1-kinase-activity-and-gene-expression-regulator
#2
Jennifer Jung, Arnab Nayak, Véronique Schaeffer, Tatjana Starzetz, Achim Klaus Kirsch, Stefan Müller, Ivan Dikic, Michel Mittelbronn, Christian Behrends
Autophagy is an intracellular recycling and degradation pathway that depends on membrane trafficking. Rab GTPases are central for autophagy but their regulation especially through the activity of Rab GEFs remains largely elusive. We employed a RNAi screen simultaneously monitoring different populations of autophagosomes and identified 34 out of 186 Rab GTPase, GAP and GEF family members as potential autophagy regulators, amongst them SMCR8. SMCR8 uses overlapping binding regions to associate with C9ORF72 or with a C9ORF72-ULK1 kinase complex holo-assembly, which function in maturation and formation of autophagosomes, respectively...
February 14, 2017: ELife
https://www.readbyqxmd.com/read/28165887/a-small-molecule-activator-induces-ulk1-modulating-autophagy-associated-cell-death-in-triple-negative-breast-cancer
#3
Liang Ouyang, Lan Zhang, Leilei Fu, Bo Liu
ULK1 (unc-51 like autophagy activating kinase 1) is well known to be required to initiate the macroautophagy/autophagy process, and thus activation of ULK1-modulating autophagy/autophagy-associated cell death (ACD) may be a possible therapeutic strategy in triple negative breast cancer (TNBC). Here, our integrated The Cancer Genome Atlas (TCGA) dataset, tissue microarray-based analyses and multiple biological evaluations together demonstrate a new small-molecule activator of ULK1 for better understanding of how ULK1, the mammalian homolog of yeast Atg1, as a potential drug target can regulate ACD by the ULK complex (ULK1-ATG13-RB1CC1/FIP200-ATG101), as well as other possible ULK1 interactors, including ATF3, RAD21 and CASP3/caspase3 in TNBC...
February 6, 2017: Autophagy
https://www.readbyqxmd.com/read/28160489/sec16-in-conventional-and-unconventional-exocytosis-working-at-the-interface-of-membrane-traffic-and-secretory-autophagy
#4
REVIEW
Bor Luen Tang
Sec16 is classically perceived to be a scaffolding protein localized to the transitional endoplasmic reticulum (tER) or the ER exit sites (ERES), and has a conserved function in facilitating coat protein II (COPII) complex-mediated ER exit. Recent findings have however pointed towards a role for Sec16 in unconventional exocytosis of certain membrane proteins, such as the Cystic fibrosis transmembrane conductance regulator (CFTR) in mammalian cells, and possibly also α-integrin in certain contexts of Drosophila development...
February 4, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28124127/acute-low-intensity-cycling-with-blood-flow-restriction-has-no-effect-on-metabolic-signaling-in-human-skeletal-muscle-compared-to-traditional-exercise
#5
William J Smiles, Miguel S Conceição, Guilherme D Telles, Mara P T Chacon-Mikahil, Cláudia R Cavaglieri, Felipe C Vechin, Cleiton A Libardi, John A Hawley, Donny M Camera
PURPOSE: Autophagy is an intracellular degradative system sensitive to hypoxia and exercise-induced perturbations to cellular bioenergetics. We determined the effects of low-intensity endurance-based exercise performed with blood-flow restriction (BFR) on cell signaling adaptive responses regulating autophagy and substrate metabolism in human skeletal muscle. METHODS: In a randomized cross-over design, nine young, healthy but physically inactive males completed three experimental trials separated by 1 week of recovery consisting of either a resistance exercise bout (REX: 4 × 10 leg press repetitions, 70% 1-RM), endurance exercise (END: 30 min cycling, 70% VO2peak), or low-intensity cycling with BFR (15 min, 40% VO2peak)...
January 25, 2017: European Journal of Applied Physiology
https://www.readbyqxmd.com/read/28118076/targeting-ampk-ulk1-mediated-autophagy-for-combating-bet-inhibitor-resistance-in-acute-myeloid-leukemia-stem-cells
#6
Ji Eun Jang, Ju-In Eom, Hoi-Kyung Jeung, June-Won Cheong, Jung Yeon Lee, Jin Seok Kim, Yoo Hong Min
Bromodomain and extraterminal domain (BET) inhibitors are promising epigenetic agents for the treatment of various subsets of acute myeloid leukemia (AML). However, the resistance of leukemia stem cells (LSCs) to BET inhibitors remains a major challenge. In this study, we evaluated the mechanisms underlying LSC resistance to the BET inhibitor JQ1. We evaluated the levels of apoptosis and macroautophagy/autophagy induced by JQ1 in LSC-like leukemia cell lines and primary CD34(+) CD38(-) leukemic blasts obtained from AML cases with normal karyotype without recurrent mutations...
January 24, 2017: Autophagy
https://www.readbyqxmd.com/read/28118060/the-molecular-mechanism-of-atg13-function-in-autophagy-induction-what-is-hidden-behind-the-data
#7
Hana Popelka, Daniel J Klionsky
Atg13 is an essential subunit of the Atg1 autophagy initiation complex in yeast and its mammalian counterpart, ATG13, is indispensable for autophagy induction by the ULK1 complex. The N terminus of the protein folds into a HORMA domain, an architecture that has been revealed by crystallography. (1-4) In human cells, the ATG13 HORMA domain interacts directly with ATG14, a subunit of the class III phosphatidylinositol 3-kinase complex. (5) In budding yeast, the HORMA of Atg13 recruits Atg14, but a direct interaction remains to be proven...
January 24, 2017: Autophagy
https://www.readbyqxmd.com/read/28115361/selective-reversible-inhibition-of-autophagy-in-hypoxic-breast-cancer-cells-promotes-pulmonary-metastasis
#8
Christopher M Dower, Neema Bhat, Edward W Wang, Hong-Gang Wang
Autophagy influences how cancer cells respond to nutrient deprivation and hypoxic stress, two hallmarks of the tumor microenvironment (TME). In this study, we explored the impact of autophagy on the pathophysiology of breast cancer cells using a novel hypoxia-dependent, reversible dominant-negative strategy to regulate autophagy at the cellular level within the TME. Suppression of autophagy via hypoxia-induced expression of the kinase-dead unc-51-like autophagy-activating kinase (ULK1) mutant K46N increased lung metastases in MDA-MB-231 xenograft mouse models...
February 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28109268/gastrin-activates-autophagy-and-increases-migration-and-survival-of-gastric-adenocarcinoma-cells
#9
Shalini V Rao, Guri Solum, Barbara Niederdorfer, Kristin G Nørsett, Geir Bjørkøy, Liv Thommesen
BACKGROUND: The peptide hormone gastrin exerts a growth-promoting effect in both normal and malignant gastrointestinal tissue. Gastrin mediates its effect via the cholecystokinin 2 receptor (CCKBR/CCK2R). Although a substantial part of the gastric adenocarcinomas express gastrin and CCKBR, the role of gastrin in tumor development is not completely understood. Autophagy has been implicated in mechanisms governing cytoprotection, tumor growth, and contributes to chemoresistance. This study explores the role of autophagy in response to gastrin in gastric adenocarcinoma cell lines...
January 21, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28105213/wogonin-induces-beclin-1-pi3k-and-reactive-oxygen-species-mediated-autophagy-in-human-pancreatic-cancer-cells
#10
Shao-Jun Li, Shi-Jie Sun, Jie Gao, Fu-Bo Sun
Wogonin is considered to be an inhibitor of myeloid cell leukemia 1 and B-cell lymphoma 2, and a potential antitumor drug due to its ability to induce apoptosis in certain cancer cells; however, few previous studies have reported on wogonin-induced autophagy. The aim of the present study was to investigate the influence of wogonin on autophagy in human pancreatic cancer cells (HPCCs), elucidate its mechanism, and identify strategies to increase its effectiveness as an anti-cancer treatment. HPCCs were treated with wogonin and autophagy was detected in the cells...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28100477/inability-to-replete-white-adipose-tissue-during-the-recovery-phase-of-sepsis-is-associated-with-increased-autophagy-apoptosis-and-proteasome-activity
#11
Kristen T Crowell, David I Soybel, Charles H Lang
Adipose tissue is an important energy depot and endocrine organ, and the degree of adiposity impacts the host response to infection. However, little is known regarding the mechanisms by which white adipose tissue (WAT) is lost acutely and then restored after resolution of sepsis. Therefore, signaling pathways governing protein synthesis, autophagy, apoptosis and the ubiquitin-proteasome were investigated to identify potential mechanisms mediating the acute (24 h) loss of WAT after cecal ligation and puncture (CLP) as well as the failure to replenish WAT during recovery (day 10)...
January 18, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28079894/mir-26-enhances-chemosensitivity-and-promotes-apoptosis-of-hepatocellular-carcinoma-cells-through-inhibiting-autophagy
#12
Fangfang Jin, Yanbo Wang, Mingzhen Li, Yanan Zhu, Hongwei Liang, Chen Wang, Feng Wang, Chen-Yu Zhang, Ke Zen, Limin Li
Hepatocellular carcinoma (HCC) generally possesses a high resistance to chemotherapy. Given that autophagy is an important factor promoting tumor chemoresistance and HCC express low level of miR-26, we aim to investigate the functional role of miR-26 in autophagy-mediated chemoresistance of HCC. We found that chemotherapeutic drug doxorubicin (Dox) induced autophagy but decreased the level of miR-26a/b in HCC cells. Activating autophagy using rapamycin can directly downregulate the level of miR-26a/b in HCC cells...
January 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28073914/serine-threonine-kinase-unc-51-like-kinase-1-ulk1-phosphorylates-the-co-chaperone-cdc37-and-thereby-disrupts-the-stability-of-cdc37-client-proteins
#13
Ran Li, Fengjie Yuan, Wan Fu, Luyao Zhang, Nan Zhang, Yanan Wang, Ke Ma, Xue Li, Lina Wang, Wei-Guo Zhu, Ying Zhao
The serine/threonine kinase Unc-51 like kinase-1 (Ulk1) is thought to be essential for induction of autophagy, an intracellular bulk degradation process that is activated by various stresses. Although several proteins have been suggested as Ulk1 substrates during autophagic process, it still remains largely unknown about Ulk1's physiological substrates. Here, by performing in vitro and in vivo phosphorylation assay, we report that the co-chaperone cell division cycle protein 37 (Cdc37) is an Ulk1 substrate...
January 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28072404/autophagic-membrane-delivery-through-atg9
#14
Yuchen Feng, Daniel J Klionsky
One of the key questions regarding macroautophagy/autophagy is the mechanism through which the transmembrane protein ATG9 functions in delivering membrane to the expanding phagophore, the sequestering compartment that matures into an autophagosome. In a recent study, Zhou et al. identified a novel mechanism that regulates ATG9 trafficking from the plasma membrane and trans-Golgi network, which involves two conserved sorting signals required for ATG9 interaction with the AP1/2 adaptor complex and phosphorylation of ATG9 at Tyr8 by SRC kinase and at Ser14 by ULK1 for proper function during basal and starvation-induced autophagy...
January 10, 2017: Cell Research
https://www.readbyqxmd.com/read/28069524/atg14-facilitated-lipophagy-in-cancer-cells-induce-er-stress-mediated-mitoptosis-through-a-ros-dependent-pathway
#15
Subhadip Mukhopadhyay, Isabel R Schlaepfer, Bryan C Bergman, Prashanta Kumar Panda, Prakash Priyadarshi Praharaj, Prajna Paramita Naik, Rajesh Agarwal, Sujit Kumar Bhutia
Understanding the dynamics of autophagy and apoptosis crosstalk in cancer progression remains a challenging task. Here, we reported how the autophagy protein ATG14 induces lipophagy-mediated mitochondrial apoptosis. The overexpression of ATG14 in HeLa cells inhibited cell viability and increased mitochondrial apoptosis and endoplasmic reticulum (ER) stress. Furthermore, inhibition of this ATG14-induced autophagy promoted apoptosis. ATG14 overexpression resulted in the accumulation of free fatty acids (FFA), with a concomitant decrease in the number of lipid droplets...
January 6, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28059666/mtorc1-mediated-nrbf2-phosphorylation-functions-as-a-switch-for-the-class-iii-ptdins3k-and-autophagy
#16
Xi Ma, Shen Zhang, Long He, Yueguang Rong, Livia Wilz Brier, Qiming Sun, Rong Liu, Weiliang Fan, She Chen, Zhenyu Yue, Joungmok Kim, Kun-Liang Guan, Defa Li, Qing Zhong
NRBF2/Atg38 has been identified as the fifth subunit of the macroautophagic/autophagic class III phosphatidylinositol 3-kinase (PtdIns3K) complex, along with ATG14/Barkor, BECN1/Vps30, PIK3R4/p150/Vps15 and PIK3C3/Vps34. However, its functional mechanism and regulation are not fully understood. Here, we report that NRBF2 is a fine tuning regulator of PtdIns3K controlled by phosphorylation. Human NRBF2 is phosphorylated by MTORC1 at S113 and S120. Upon nutrient starvation or MTORC1 inhibition, NRBF2 phosphorylation is diminished...
January 6, 2017: Autophagy
https://www.readbyqxmd.com/read/28059583/mir7-3hg-a-myc-dependent-modulator-of-cell-proliferation-inhibits-autophagy-by-a-regulatory-loop-involving-ambra1
#17
Mariacristina Capizzi, Flavie Strappazzon, Valentina Cianfanelli, Elena Papaleo, Francesco Cecconi
Macroautophagy/autophagy is a tightly regulated intracellular catabolic pathway involving the lysosomal degradation of cytoplasmic organelles and proteins to be recycled into metabolic precursors. AMBRA1 (autophagy and Beclin 1 regulator 1) has a central role in the autophagy signaling network; it acts upstream of MTORC1-dependent autophagy by stabilizing the kinase ULK1 (unc-51 like autophagy activating kinase 1) and by favoring autophagosome core complex formation. AMBRA1 also regulates the cell cycle by modulating the activity of the phosphatase PPP2/PP2A (protein phosphatase 2) and degradation of MYC...
January 6, 2017: Autophagy
https://www.readbyqxmd.com/read/28059582/prkcd-pkc%C3%AE-contributes-to-nephrotoxicity-during-cisplatin-chemotherapy-by-suppressing-autophagy
#18
Dongshan Zhang, Xuan Xu, Zheng Dong
Nephrotoxicity is a major side effect during chemotherapy with cisplatin and related platinum compounds. Previous work unveiled a role of PRKCD/PKCδ (protein kinase C delta) in cisplatin-induced nephrotoxicity; however, the underlying mechanism was largely unknown. Our recent work showed that PRKCD may suppress macroautophagy/autophagy, a cytoprotective mechanism, to promote kidney tubule cell death during cisplatin treatment. Interestingly, PRKCD may do so by phosphorylating AKT, which further phosphorylates MTOR to repress ULK1...
January 6, 2017: Autophagy
https://www.readbyqxmd.com/read/28035578/the-bax-gene-as-a-candidate-for-negative-autophagy-related-genes-regulator-on-mrna-levels-in-colorectal-cancer
#19
Justyna Gil, David Ramsey, Elzbieta Szmida, Przemyslaw Leszczynski, Pawel Pawlowski, Marek Bebenek, Maria M Sasiadek
Autophagy is a catabolic process, which is involved in the maintenance of intracellular homeostasis by degrading redundant molecules and organelles. Autophagy begins with the formation of a double-membrane phagophore, followed by its enclosure, thus leading to the appearance of an autophagosome which fuses with lysosome. This process is highly conserved, precisely orchestrated and regulated by autophagy-related genes. Recently, autophagy has been widely studied in different types of cancers, including colorectal cancer...
February 2017: Medical Oncology
https://www.readbyqxmd.com/read/28032867/regulation-of-er-stress-induced-autophagy-by-gsk3%C3%AE-tip60-ulk1-pathway
#20
Tiejian Nie, Shaosong Yang, Hongwei Ma, Lei Zhang, Fangfang Lu, Kai Tao, Ronglin Wang, Ruixin Yang, Lu Huang, Zixu Mao, Qian Yang
Endoplasmic reticulum (ER) stress is involved in many cellular processes. Emerging evidence suggests that ER stress can trigger autophagy; however, the mechanisms by which ER stress regulates autophagy and its role in this condition are not fully understood. HIV Tat-interactive protein, 60 kDa (TIP60) is a newly discovered acetyltransferase that can modulate autophagy flux by activating ULK1 upon growth factor deprivation. In this study, we investigated the mechanisms by which ER stress induces autophagy...
December 29, 2016: Cell Death & Disease
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