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https://www.readbyqxmd.com/read/27911840/multistep-regulation-of-autophagy-by-wnk1
#1
Sachith Gallolu Kankanamalage, A-Young Lee, Chonlarat Wichaidit, Andres Lorente-Rodriguez, Akansha M Shah, Steve Stippec, Angelique W Whitehurst, Melanie H Cobb
The with-no-lysine (K) (WNK) kinases are an atypical family of protein kinases that regulate ion transport across cell membranes. Mutations that result in their overexpression cause hypertension-related disorders in humans. Of the four mammalian WNKs, only WNK1 is expressed throughout the body. We report that WNK1 inhibits autophagy, an intracellular degradation pathway implicated in several human diseases. Using small-interfering RNA-mediated WNK1 knockdown, we show autophagosome formation and autophagic flux are accelerated...
November 28, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27909227/castration-alters-protein-balance-following-high-frequency-muscle-contraction
#2
Jennifer L Steiner, David H Fukuda, Michael L Rossetti, Jay R Hoffman, Bradley S Gordon
Resistance exercise increases muscle mass by shifting protein balance in favor of protein accretion. Androgens independently alter protein balance, but it is unknown whether androgens alter this measure following resistance exercise. To answer this, male mice were subjected to sham or castration surgery 7-8 weeks prior to undergoing a bout of unilateral, high frequency, electrically induced muscle contractions in the fasted or refed state. Puromycin was injected 30 min prior to sacrifice to measure protein synthesis...
December 1, 2016: Journal of Applied Physiology
https://www.readbyqxmd.com/read/27887947/berberine-enhances-the-ampk-activation-and-autophagy-and-mitigates-high-glucose-induced-apoptosis-of-mouse-podocytes
#3
Yingli Jin, Shuping Liu, Qingshan Ma, Dong Xiao, Li Chen
High glucose concentration can induce injury of podocytes and berberine has a potent activity against diabetic nephropathy. However, whether and how berberine can inhibit high glucose-mediated injury of podocytes have not been clarified. This study tested the effect of berberine on high glucose-mediated apoptosis and the AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR) activation and autophagy in podocytes. The results indicated that berberine significantly mitigated high glucose-decreased cell viability, and nephrin and podocin expression as well as apoptosis in mouse podocytes...
November 22, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27886437/the-microrna-99-family-modulates-hepatitis-b-virus-replication-by-promoting-igf-1r-pi3k-akt-mtor-ulk1-signaling-induced-autophagy
#4
Yong Lin, Wanyu Deng, Jinke Pang, Thekla Kemper, Jing Hu, Jian Yin, Jiming Zhang, Mengji Lu
MicroRNAs (miRNAs) are small highly conserved noncoding RNAs that are widely expressed in multicellular organisms and participate in the regulation of various cellular processes including autophagy and viral replication. Evidently, miRNAs are able to modulate host gene expression and thereby inhibit or enhance hepatitis B virus (HBV) replication. The miR-99 family members are highly expressed in the liver. Interestingly, the plasma levels of miR-99 family in the peripheral blood correspond with HBV DNA loads...
November 25, 2016: Cellular Microbiology
https://www.readbyqxmd.com/read/27879319/amp-activated-kinase-ampk-promotes-innate-immunity-and-antiviral-defense-through-modulation-of-stimulator-of-interferon-genes-sting-signaling
#5
Daniel Prantner, Darren J Perkins, Stefanie N Vogel
The host protein Stimulator of Interferon Genes (STING) has been shown to be essential for recognition of both viral and intracellular bacterial pathogens, but its regulation remains unclear. Previously, we reported that mitochondrial membrane potential regulates STING-dependent IFN-beta induction independently of ATP synthesis. Since mitochondrial membrane potential controls calcium homeostasis, and AMP-activated protein kinase (AMPK) is regulated, in part, by intracellular calcium, we postulated that AMPK participates in STING activation; however, its role has yet to be been defined...
November 22, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27871932/s100a10-regulates-ulk1-localization-to-er-mitochondria-contact-sites-in-ifn-%C3%AE-triggered-autophagy
#6
Ying-Da Chen, Yi-Ting Fang, Chih-Peng Chang, Chiou-Feng Lin, Li-Jin Hsu, Shang-Rung Wu, Yen-Chi Chiu, Robert Anderson, Yee-Shin Lin
During the process of autophagy, the autophagy-related (ATG) proteins are translocated to autophagosome formation sites. Here, we demonstrate that S100A10 is required for ULK1 localization to autophagosome formation sites. Silencing of S100A10 reduces IFN-γ-induced autophagosome formation. We also determined the role of annexin A2 (ANXA2), a binding partner of S100A10, which has been reported to promote phagophore assembly. Silencing of ANXA2 reduced S100A10 expression. However, overexpression of S100A10 in ANXA2-silenced cells was still able to enhance autophagosome formation, suggesting that ANXA2 regulates IFN-γ-induced autophagy through S100A10...
November 18, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/27870268/digesting-cytotoxic-stressors-an-unconventional-mechanism-to-induce-autophagy
#7
Christine R Langlois, Thomas Wollert
Autophagy is an essential and fundamental pathway that clears unwanted or damaged material from the cell. Initiation of autophagy was previously shown to be dependent on the Ulk1/2 kinase complex. In this issue of The FEBS Journal, Braden and Neufeld investigated the Ulk3 homolog in Drosophila, and proposed a novel, Ulk1/2 independent pathway for autophagy initiation.
November 2016: FEBS Journal
https://www.readbyqxmd.com/read/27869123/a-systems-study-reveals-concurrent-activation-of-ampk-and-mtor-by-amino-acids
#8
Piero Dalle Pezze, Stefanie Ruf, Annika G Sonntag, Miriam Langelaar-Makkinje, Philip Hall, Alexander M Heberle, Patricia Razquin Navas, Karen van Eunen, Regine C Tölle, Jennifer J Schwarz, Heike Wiese, Bettina Warscheid, Jana Deitersen, Björn Stork, Erik Fäßler, Sascha Schäuble, Udo Hahn, Peter Horvatovich, Daryl P Shanley, Kathrin Thedieck
Amino acids (aa) are not only building blocks for proteins, but also signalling molecules, with the mammalian target of rapamycin complex 1 (mTORC1) acting as a key mediator. However, little is known about whether aa, independently of mTORC1, activate other kinases of the mTOR signalling network. To delineate aa-stimulated mTOR network dynamics, we here combine a computational-experimental approach with text mining-enhanced quantitative proteomics. We report that AMP-activated protein kinase (AMPK), phosphatidylinositide 3-kinase (PI3K) and mTOR complex 2 (mTORC2) are acutely activated by aa-readdition in an mTORC1-independent manner...
November 21, 2016: Nature Communications
https://www.readbyqxmd.com/read/27864418/ampk-ulk1-mediated-autophagy-confers-resistance-to-bet-inhibitor-jq1-in-acute-myeloid-leukemia-stem-cells
#9
Ji Eun Jang, Ju In Eom, Hoi Kyung Jeung, June-Won Cheong, Jung Yeon Lee, Jin Seok Kim, Yoo Hong Min
PURPOSE: 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. EXPERIMENTAL DESIGN: We evaluated the levels of apoptosis and 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...
November 18, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27846905/rapamycin-regulates-autophagy-and-cell-adhesion-in-induced-pluripotent-stem-cells
#10
Areechun Sotthibundhu, Katya McDonagh, Alexander von Kriegsheim, Amaya Garcia-Munoz, Agnieszka Klawiter, Kerry Thompson, Kapil Dev Chauhan, Janusz Krawczyk, Veronica McInerney, Peter Dockery, Michael J Devine, Tilo Kunath, Frank Barry, Timothy O'Brien, Sanbing Shen
BACKGROUND: Cellular reprogramming is a stressful process, which requires cells to engulf somatic features and produce and maintain stemness machineries. Autophagy is a process to degrade unwanted proteins and is required for the derivation of induced pluripotent stem cells (iPSCs). However, the role of autophagy during iPSC maintenance remains undefined. METHODS: Human iPSCs were investigated by microscopy, immunofluorescence, and immunoblotting to detect autophagy machinery...
November 15, 2016: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27846372/loss-of-ulk1-increases-rps6kb1-ncor1-repression-of-nr1h-lxr-mediated-scd1-transcription-and-augments-lipotoxicity-in-hepatic-cells
#11
Rohit Anthony Sinha, Brijesh K Singh, Jin Zhou, Sherwin Xie, Benjamin L Farah, Ronny Lesmana, Kenji Ohba, Madhulika Tripathi, Sujoy Ghosh, Anthony N Hollenberg, Paul M Yen
Lipotoxicity caused by saturated fatty acids (SFAs) induces tissue damage and inflammation in metabolic disorders. SCD1 (stearoyl-Coenzyme A desaturase 1) converts SFAs to mono-unsaturated fatty acids (MUFAs) that are incorporated into triglycerides and stored in lipid droplets. SCD1 thus helps protect hepatocytes from lipotoxicity and its reduced expression is associated with increased lipotoxic injury in cultured hepatic cells and mouse models. To further understand the role of SCD1 in lipotoxicity, we examined the regulation of Scd1 in hepatic cells treated with palmitate, and found that NR1H/LXR (nuclear receptor subfamily 1 group H) ligand, GW3965, induced Scd1 expression and lipid droplet formation to improve cell survival...
November 15, 2016: Autophagy
https://www.readbyqxmd.com/read/27837193/intact-initiation-of-autophagy-and-mitochondrial-fission-by-acute-exercise-in-skeletal-muscle-of-patientswith-type-2-diabetes
#12
Rikke Kruse, Andreas J T Pedersen, Jonas M Kristensen, Stine J Petersson, Jørgen F P Wojtaszewski, Kurt Højlund
AIMS: Type 2 diabetes (T2D) is characterized by insulin resistance, mitochondrial dysregulation, and, in some studies, exercise resistance in skeletal muscle. Regulation of autophagy and mitochondrial dynamics during exercise and recovery is important for skeletal muscle homeostasis, and these responses may be altered in T2D. MATERIALS AND METHODS: We examined the effect of acute exercise on markers of autophagy and mitochondrial fusion and fission in skeletal muscle biopsies from patients with T2D (n=13) and weight-matched controls (n=14) before, immediately after and 3h after an acute bout of exercise...
November 11, 2016: Clinical Science (1979-)
https://www.readbyqxmd.com/read/27800610/lipocalin-2-ngal-attenuates-autophagy-to-exacerbate-cardiac-apoptosis-induced-by-myocardial-ischemia
#13
Hye Kyoung Sung, Yee Kwan Chan, Meng Han, James Won Suk Jahng, Erfei Song, Danielson Eric, Thorsten Berger, Tak W Mak, Gary Sweeney
Lipocalin-2 (Lcn2; also termed neutrophil gelatinase-associated lipocalin (NGAL)) levels correlate positively with heart failure (HF) yet mechanisms via which Lcn2 contributes to the pathogenesis of HF remian unclear. In this study we used coronary artery ligation surgery to induce ischemia in wild type (wt) mice and this induced a significant increase in myocardial Lcn2. We then compared wt and Lcn2 knockout (KO) mice and observed that wt mice showed greater ischemia-induced caspase-3 activation and DNA damage measured by TUNEL than Lcn2KO mice...
November 1, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27799485/protein-kinase-c%C3%AE-suppresses-autophagy-to-induce-kidney-cell-apoptosis-in-cisplatin-nephrotoxicity
#14
Dongshan Zhang, Jian Pan, Xudong Xiang, Yu Liu, Guie Dong, Man J Livingston, Jian-Kang Chen, Xiao-Ming Yin, Zheng Dong
Nephrotoxicity is a major adverse effect in cisplatin chemotherapy, and renoprotective approaches are unavailable. Recent work unveiled a critical role of protein kinase Cδ (PKCδ) in cisplatin nephrotoxicity and further demonstrated that inhibition of PKCδ not only protects kidneys but enhances the chemotherapeutic effect of cisplatin in tumors; however, the underlying mechanisms remain elusive. Here, we show that cisplatin induced rapid activation of autophagy in cultured kidney tubular cells and in the kidneys of injected mice...
October 31, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27791467/identification-of-natural-products-with-neuronal-and-metabolic-benefits-through-autophagy-induction
#15
Yuying Fan, Nan Wang, Altea Rocchi, Weiran Zhang, Robert Vassar, Yifa Zhou, Congcong He
Autophagy is a housekeeping lysosomal degradation pathway important for cellular survival, homeostasis and function. Various disease models have shown that upregulation of autophagy may be beneficial to combat disease pathogenesis. However, despite several recently reported small-molecule screens for synthetic autophagy inducers, natural chemicals of diverse structures and functions have not been included in the synthetic libraries, and characterization of their roles in autophagy has been lacking. To discover novel autophagy-regulating compounds and study their therapeutic mechanisms, we used analytic chemistry approaches to isolate natural phytochemicals from a reservoir of medicinal plants used in traditional remedies...
October 28, 2016: Autophagy
https://www.readbyqxmd.com/read/27783190/a-novel-tetra-primer-arms-pcr-based-assay-for-genotyping-snp-rs12303764-g-t-of-human-unc-51-like-kinase-1-gene
#16
Rohit Randhawa, Ajay Duseja, Harish Changotra
Various case-control studies have shown association of single nucleotide polymorphism rs12303764(G/T) in ULK1 with crohn's disease. The techniques used in these studies were time consuming, complicated and require sophisticated/expensive instruments. Therefore, in order to overcome these problems, we have developed a new, rapid and cost effective Tetra-primer ARMS-PCR assay to genotype single nucleotide polymorphism rs12303764(G/T) of ULK1 gene. We manually designed allele specific primers. DNA fragment amplified using outer primers was sequenced to obtain samples with known genotypes (GG, GT and TT) for further use in the development of T-ARMS-PCR assay...
October 25, 2016: Molecular Biology Reports
https://www.readbyqxmd.com/read/27774051/c9orf72-s-interaction-with-rab-gtpases-modulation-of-membrane-traffic-and-autophagy
#17
Bor L Tang
Hexanucleotide repeat expansion in an intron of Chromosome 9 open reading frame 72 (C9orf72) is the most common genetic cause of Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD). While functional haploinsufficiency of C9orf72 resulting from the mutation may play a role in ALS/FTD, the actual cellular role of the protein has been unclear. Recent findings have now shown that C9orf72 physically and functionally interacts with multiple members of the Rab small GTPases family, consequently exerting important influences on cellular membrane traffic and the process of autophagy...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27768524/c9orf72-plays-a-central-role-in-rab-gtpase-dependent-regulation-of-autophagy
#18
Christopher P Webster, Emma F Smith, Andrew J Grierson, Kurt J De Vos
A GGGGCC hexanucleotide repeat expansion in the first intron of the C9orf72 gene is the most common genetic defect associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (C9ALS/FTD). Haploinsufficiency and a resulting loss of C9orf72 protein function has been suggested as a possible pathogenic mechanism in C9ALS/FTD. C9ALS/FTD patients exhibit specific ubiquitin and p62/sequestosome-1 positive but TDP-43 negative inclusions in the cerebellum and hippocampus, indicating possible autophagy deficits in these patients...
October 21, 2016: Small GTPases
https://www.readbyqxmd.com/read/27742708/a-new-molecular-link-between-defective-autophagy-and-erythroid-abnormalities-in-chorea-acanthocytosis
#19
Francesca Lupo, Elena Tibaldi, Alessandro Matte, Alok K Sharma, Anna Maria Brunati, Seth L Alper, Carlo Zancanaro, Donatella Benati, Angela Siciliano, Mariarita Bertoldi, Francesca Zonti, Alexander Storch, Ruth H Walker, Adrian Danek, Benedikt Bader, Andreas Hermann, Lucia De Franceschi
Chorea-acanthocytosis is one of the hereditary neurodegenerative disorders known as the neuroacanthocytoses. Chorea-acanthocytosis is characterized by circulating acanthocytes deficient in chorein, a protein of unknown function. We report here for the first time that chorea-acanthocytosis red-cells are characterized by impaired autophagy, with cytoplasmic accumulation of active Lyn and of autophagy-related proteins Ulk1, Atg7. In chorea-acanthocytosis erythrocytes, active Lyn is sequestered by HSP90-70 to form high-molecular-weight complexes that stabilize and protect Lyn from its proteasomal degradation, contributing to toxic Lyn accumulation...
October 14, 2016: Blood
https://www.readbyqxmd.com/read/27740626/the-lncrna-hotairm1-regulates-the-degradation-of-pml-rara-oncoprotein-and-myeloid-cell-differentiation-by-enhancing-the-autophagy-pathway
#20
Zhen-Hua Chen, Wen-Tao Wang, Wei Huang, Ke Fang, Yu-Meng Sun, Shu-Rong Liu, Xue-Qun Luo, Yue-Qin Chen
Increasing evidence has indicated that long noncoding RNAs (lncRNAs) are of great importance in different cell contexts. However, only a very small number of lncRNAs have been experimentally validated and functionally annotated during human hematopoiesis. Here, we report an lncRNA, HOTAIRM1, which is associated with myeloid differentiation and has pivotal roles in the degradation of oncoprotein PML-RARA and in myeloid cell differentiation by regulating autophagy pathways. We first revealed that HOTAIRM1 has different variants that are expressed at different levels in cells and that the expression pattern of HOTAIRM1 is closely related to that of the PML-RARA oncoprotein in acute promyelocytic leukemia (APL) patients...
October 14, 2016: Cell Death and Differentiation
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