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https://www.readbyqxmd.com/read/28109823/divergent-regulation-of-insulin-like-growth-factor-binding-protein-genes-in-cultured-atlantic-salmon-myotubes-under-different-models-of-catabolism-and-anabolism
#1
Daniel Garcia de la Serrana, Eduardo N Fuentes, Samuel A M Martin, Ian A Johnston, Daniel J Macqueen
Much attention has been given to insulin-like growth factor (Igf) pathways that regulate the balance of skeletal muscle protein synthesis and breakdown in response to a range of extrinsic and intrinsic signals. However, we have a less complete understanding of how the same signals modulate muscle mass upstream of such signalling, through a family of functionally-diverse Igf-binding proteins (Igfbps) that modify the availability of Igfs to the cell receptor Igf1r. We exposed cultured myotubes from Atlantic salmon (Salmo salar L...
January 18, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28107776/activity-based-probes-for-the-multicatalytic-proteasome
#2
REVIEW
David S Hewings, John A Flygare, Ingrid E Wertz, Matthew Bogyo
Proteasomes are multisubunit protease complexes responsible for degrading most intracellular proteins. In addition to removing damaged proteins, they regulate many important cellular processes through the controlled degradation of transcription factors, cell cycle regulators and enzymes. Eukaryotic proteasomes have three catalytic subunits, β1, β2 and β5, that each have different substrate specificities. Additionally, although we know that diverse cell types express proteasome variants with distinct activity and specificity profiles, the functions of these different pools of proteasomes are not fully understood...
January 20, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28107521/differential-roles-of-axin1-and-axin2-in-tankyrase-inhibitor-induced-formation-of-degradasomes-and-%C3%AE-catenin-degradation
#3
Tor Espen Thorvaldsen, Nina Marie Pedersen, Eva Maria Wenzel, Harald Stenmark
Inhibition of the tankyrase enzymes (TNKS1 and TNKS2) has recently been shown to induce highly dynamic assemblies of β-catenin destruction complex components known as degradasomes, which promote degradation of β-catenin and reduced Wnt signaling activity in colorectal cancer cells. AXIN1 and AXIN2/Conductin, the rate-limiting factors for the stability and function of endogenous destruction complexes, are stabilized upon TNKS inhibition due to abrogated degradation of AXIN by the proteasome. Since the role of AXIN1 versus AXIN2 as scaffolding proteins in the Wnt signaling pathway still remains incompletely understood, we sought to elucidate their relative contribution in the formation of degradasomes, as these protein assemblies most likely represent the morphological and functional correlates of endogenous β-catenin destruction complexes...
2017: PloS One
https://www.readbyqxmd.com/read/28106854/the-effect-of-polyphenols-on-protein-degradation-pathways-implications-for-neuroprotection
#4
REVIEW
Parvana Hajieva
Human neurodegenerative diseases are accompanied by accumulation of heavily oxidized and aggregated proteins. However, the exact molecular reason is not fully elucidated yet. Insufficient cellular protein quality control is thought to play an important role in accumulating covalently oxidized misfolded proteins. Pharmacologically active polyphenols and their derivatives exhibit potential for preventive and therapeutic purposes against protein aggregation during neurodegeneration. Although these compounds act on various biochemical pathways, their role in stabilizing the protein degradation machinery at different stages may be an attractive therapeutical strategy to halt the accumulation of misfolded proteins...
January 19, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28106301/uxt-is-a-lox-pp-interacting-protein-that-modulates-estrogen-receptor-alpha-activity-in-breast-cancer-cells
#5
Nuria Sánchez-Morgan, Kathrin H Kirsch, Philip C Trackman, Gail E Sonenshein
The lysyl oxidase proenzyme propeptide region (LOX-PP) is a tumor suppressor protein whose mechanism of action is not completely understood. Here, the Ubiquitously eXpressed Transcript (UXT) was identified in a yeast two-hybrid assay with LOX-PP as bait and confirmed as a novel LOX-PP associating protein. UXT, a prefoldin-like protein, is ubiquitous in human and mouse. Since UXT modulates androgen receptor transcriptional activity in prostate cancer, we studied its role in breast cancer. Breast tumors and derived cell lines overexpressed UXT...
January 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28106073/high-resolution-cryo-em-structure-of-the-proteasome-in-complex-with-adp-alfx
#6
Zhanyu Ding, Zhenglin Fu, Cong Xu, Yifan Wang, Yanxing Wang, Junrui Li, Liangliang Kong, Jinhuan Chen, Na Li, Rongguang Zhang, Yao Cong
The 26S proteasome is an ATP-dependent dynamic 2.5 MDa protease that regulates numerous essential cellular functions through degradation of ubiquitinated substrates. Here we present a near-atomic-resolution cryo-EM map of the S. cerevisiae 26S proteasome in complex with ADP-AlFx. Our biochemical and structural data reveal that the proteasome-ADP-AlFx is in an activated state, displaying a distinct conformational configuration especially in the AAA-ATPase motor region. Noteworthy, this map demonstrates an asymmetric nucleotide binding pattern with four consecutive AAA-ATPase subunits bound with nucleotide...
January 20, 2017: Cell Research
https://www.readbyqxmd.com/read/28105938/the-influence-of-pro-longevity-gene-gclc-overexpression-on-the-age-dependent-changes-in-drosophila-transcriptome-and-biological-functions
#7
Alexey Moskalev, Mikhail Shaposhnikov, Ekaterina Proshkina, Alexey Belyi, Alexander Fedintsev, Svetlana Zhikrivetskaya, Zulfiya Guvatova, Asiya Sadritdinova, Anastasia Snezhkina, George Krasnov, Anna Kudryavtseva
BACKGROUND: Transcriptional changes that contribute to the organism's longevity and prevent the age-dependent decline of biological functions are not well understood. Here, we overexpressed pro-longevity gene encoding glutamate-cysteine ligase catalytic subunit (Gclc) and analyzed age-dependent changes in transcriptome that associated with the longevity, stress resistance, locomotor activity, circadian rhythmicity, and fertility. RESULTS: Here we reproduced the life extension effect of neuronal overexpression of the Gclc gene and investigated its influence on the age-depended dynamics of transcriptome and biological functions such as fecundity, spontaneous locomotor activity and circadian rhythmicity, as well as on the resistance to oxidative, proteotoxic and osmotic stresses...
December 28, 2016: BMC Genomics
https://www.readbyqxmd.com/read/28105936/pathways-of-aging-comparative-analysis-of-gene-signatures-in-replicative-senescence-and-stress-induced-premature-senescence
#8
Kamil C Kural, Neetu Tandon, Mikhail Skoblov, Olga V Kel-Margoulis, Ancha V Baranova
BACKGROUND: In culturing normal diploid cells, senescence may either happen naturally, in the form of replicative senescence, or it may be a consequence of external challenges such as oxidative stress. Here we present a comparative analysis aimed at reconstruction of molecular cascades specific for replicative (RS) and stressinduced senescence (SIPS) in human fibroblasts. RESULTS: An involvement of caspase-3/keratin-18 pathway and serine/threonine kinase Aurora A/ MDM2 pathway was shared between RS and SIPS...
December 28, 2016: BMC Genomics
https://www.readbyqxmd.com/read/28104914/docosahexaenoic-acid-mediated-protein-aggregates-may-reduce-proteasome-activity-and-delay-myotube-degradation-during-muscle-atrophy-in-vitro
#9
Seung Kyun Shin, Ji Hyeon Kim, Jung Hoon Lee, Young Hoon Son, Min Wook Lee, Hak Joong Kim, Sue Ah Noh, Kwang Pyo Kim, In-Gyu Kim, Min Jae Lee
Proteasomes are the primary degradation machinery for oxidatively damaged proteins that compose a class of misfolded protein substrates. Cellular levels of reactive oxygen species increase with age and this cellular propensity is particularly harmful when combined with the age-associated development of various human disorders including cancer, neurodegenerative disease and muscle atrophy. Proteasome activity is reportedly downregulated in these disease conditions. Herein, we report that docosahexaenoic acid (DHA), a major dietary omega-3 polyunsaturated fatty acid, mediates intermolecular protein cross-linkages through oxidation, and the resulting protein aggregates potently reduce proteasomal activity both in vitro and in cultured cells...
January 20, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28104755/n-glycosylation-of-human-sphingomyelin-phosphodiesterase-acid-like-3a-smpdl3a-is-essential-for-stability-secretion-and-activity
#10
Mathew Traini, Raani Kumaran, Morten Thaysen-Andersen, Maaike Kockx, Wendy Jessup, Leonard Kritharides
Sphingomyelin phosphodiesterase acid-like 3A (SMPDL3A) is a recently identified phosphodiesterase, which is a secreted N -linked glycoprotein. SMPDL3A is highly homologous to acid sphingomyelinase (aSMase), but unlike aSMase can not cleave sphingomyelin. Rather, SMPDL3A hydrolyzes nucleotide tri- and diphosphates and their derivatives. While recent structural studies have shed light on these unexpected substrate preferences, many other aspects of SMPDL3A biology which may give insight into its function in vivo remain obscure...
January 19, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28104751/exercise-training-decreases-nadph-oxidase-activity-and-restores-skeletal-muscle-mass-in-heart-failure-rats
#11
Telma F Cunha, Luiz Roberto Grassman Bechara, Aline V N Bacurau, Paulo R Jannig, Vanessa Azevedo Voltarelli, Paulo M Dourado, Andrea R Vasconcelos, Cristóforo Scavone, Julio C B Ferreira, Patricia C Brum
We have recently demonstrated that NADPH oxidase hyperactivity, NF-κB activation and increased p38 phosphorylation lead to atrophy of glycolytic muscle in heart failure (HF). Aerobic exercise training (AET) is an efficient strategy to counteract skeletal muscle atrophy in this syndrome. Therefore, we tested whether AET would regulate muscle redox balance and protein degradation by decreasing NADPH oxidase hyperactivity, reestablishing NF-κB signaling, p38 phosphorylation and proteasome activity in plantaris muscle of myocardial infarcted-induced HF (MI) rats...
January 19, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28104575/modulation-of-proteostasis-by-transcription-factor-nrf2-and-impact-in-neurodegenerative-diseases
#12
REVIEW
Marta Pajares, Antonio Cuadrado, Ana I Rojo
Neurodegenerative diseases are linked to the accumulation of specific protein aggregates, suggesting an intimate connection between injured brain and loss of proteostasis. Proteostasis refers to all the processes by which cells control the abundance and folding of the proteome thanks to a wide network that integrates the regulation of signaling pathways, gene expression and protein degradation systems. This review attempts to summarize the most relevant findings about the transcriptional modulation of proteostasis exerted by the transcription factor NRF2 (nuclear factor (erythroid-derived 2)-like 2)...
January 10, 2017: Redox Biology
https://www.readbyqxmd.com/read/28104499/methylene-blue-increases-the-amount-of-hsf1-through-promotion-of-pka-mediated-increase-in-hsf1-p300-interaction
#13
Chao Huang, Wenfeng Hu, Jili Wang, Lijuan Tong, Xu Lu, Feng Wu, Yong Ling, Bo Jiang, Wei Zhang, Zhuo Chen, Yibin Qin, Rongrong Yang
Heat shock factor 1 (HSF1) critically contributes to the host defense, and its amount determines the mobilization efficiency of HSF1 under stress conditions. To date, how HSF1 amount is regulated remains largely unknown. We found that methylene blue (MB), an anti-oxidative and anti-inflammatory agent, increased the amount of HSF1 in BV-2 microglia, primary microglia, astrocytes, neurons and vital organs. The increased HSF1 contributed to a more increase in nuclear translocation of HSF1, association of HSF1 with heat shock protein 70 (Hsp70) promoters and Hsp70 expression levels, and also induced a synergistic protection against oxidative stress-induced injuries in MB and heat shock-treated cells...
January 16, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28104457/genetic-deletion-of-soluble-epoxide-hydrolase-provides-cardioprotective-responses-following-myocardial-infarction-in-aged-mice
#14
REVIEW
K Lockhart Jamieson, Victor Samokhvalov, Maria Akhnokh, Kyra Lee, Woo Jung Cho, Abhijit Takawale, Xiuhua Wang, Zamaneh Kassiri, John M Seubert
BACKGROUND: Pathophysiological responses, including cardiovascular complications, often alter with age. Cardioprotective effects of epoxyeicosatrienoic acids (EETs) toward acute myocardial ischemia-reperfusion injury have been well documented. However, biological relevance of EET-evoked cardioprotection in the ageing myocardium remains unknown. EETs are metabolized to less active metabolites by the enzyme soluble epoxide hydrolase (sEH). This study uses permanent occlusion of the left anterior descending artery (LAD) in young and aged sEH null and WT mice to compare cardiac and mitochondrial function following ischemic injury...
January 16, 2017: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/28102523/the-effect-of-superparamagnetic-iron-oxide-nanoparticle-surface-charge-on-antigen-cross-presentation
#15
Yongbin Mou, Yun Xing, Hongyan Ren, Zhihua Cui, Yu Zhang, Guangjie Yu, Walter J Urba, Qingang Hu, Hongming Hu
Magnetic nanoparticles (NPs) of superparamagnetic iron oxide (SPIO) have been explored for different kinds of applications in biomedicine, mechanics, and information. Here, we explored the synthetic SPIO NPs as an adjuvant on antigen cross-presentation ability by enhancing the intracellular delivery of antigens into antigen presenting cells (APCs). Particles with different chemical modifications and surface charges were used to study the mechanism of action of antigen delivery. Specifically, two types of magnetic NPs, γFe2O3/APTS (3-aminopropyltrimethoxysilane) NPs and γFe2O3/DMSA (meso-2, 3-Dimercaptosuccinic acid) NPs, with the same crystal structure, magnetic properties, and size distribution were prepared...
December 2017: Nanoscale Research Letters
https://www.readbyqxmd.com/read/28102468/mutation-of-the-herc-1-ubiquitin-ligase-impairs-associative-learning-in-the-lateral-amygdala
#16
Eva Mª Pérez-Villegas, José V Negrete-Díaz, Mª Elena Porras-García, Rocío Ruiz, Angel M Carrión, Antonio Rodríguez-Moreno, José A Armengol
Tambaleante (tbl/tbl) is a mutant mouse that carries a spontaneous Gly483Glu substitution in the HERC1 (HECT domain and RCC1 domain) E3 ubiquitin ligase protein (HERC1). The tbl/tbl mutant suffers an ataxic syndrome given the almost complete loss of cerebellar Purkinje cells during adult life. More recent analyses have identified alterations at neuromuscular junctions in these mice, as well as in other neurons of the central nervous system, such as motor neurons in the spinal cord, or pyramidal neurons in the hippocampal CA3 region and the neocortex...
January 19, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28102346/human-p53-interacts-with-the-elongating-rnapii-complex-and-is-required-for-the-release-of-actinomycin-d-induced-transcription-blockage
#17
Barbara N Borsos, Ildikó Huliák, Hajnalka Majoros, Zsuzsanna Ujfaludi, Ákos Gyenis, Peter Pukler, Imre M Boros, Tibor Pankotai
The p53 tumour suppressor regulates the transcription initiation of selected genes by binding to specific DNA sequences at their promoters. Here we report a novel role of p53 in transcription elongation in human cells. Our data demonstrate that upon transcription elongation blockage, p53 is associated with genes that have not been reported as its direct targets. p53 could be co-immunoprecipitated with active forms of DNA-directed RNA polymerase II subunit 1 (RPB1), highlighting its association with the elongating RNA polymerase II...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28101649/molecular-mechanism-of-sarcopenia-and-cachexia-recent-research-advances
#18
REVIEW
Kunihiro Sakuma, Wataru Aoi, Akihiko Yamaguchi
Skeletal muscle provides a fundamental basis for human function, enabling locomotion and respiration. Muscle loss occurs as a consequence of several chronic diseases (cachexia) and normal aging (sarcopenia). Although many negative regulators (atrogin-1, muscle ring finger-1, nuclear factor-kappaB (NF-κB), myostatin, etc.) have been proposed to enhance protein degradation during both sarcopenia and cachexia, the adaptation of these mediators markedly differs within both conditions. Sarcopenia and cachectic muscles have been demonstrated to be abundant in myostatin-linked molecules...
January 19, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28101210/ube2t-silencing-suppresses-proliferation-and-induces-cell-cycle-arrest-and-apoptosis-in-bladder-cancer-cells
#19
Yan Qing Gong, Ding Peng, Xiang Hui Ning, Xin Yu Yang, Xue Song Li, Li Qun Zhou, Ying Lu Guo
Ubiquitin-conjugating enzyme E2T (UBE2T), a member of the ubiquitin-conjugating E2 family in the ubiquitin-proteasome pathway, has been reported to be overexpressed in certain tumor types and to have an important role in the Fanconi anemia pathway. In the present study, the expression of UBE2T and its association with bladder cancer were investigated; to the best of our knowledge, this has not been reported previously. Immunohistochemistry and western blot analysis demonstrated that UBE2T was significantly upregulated in bladder cancer tissues and cell lines compared with adjacent normal bladder tissues and a normal human urinary tract epithelial cell line, respectively...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28101194/inhibition-of-nedd8-and-fat10-ligase-activities-through-the-degrading-enzyme-nedd8-ultimate-buster-1-a-potential-anticancer-approach
#20
Ka-Liong Tan, Francesco Pezzella
The capabilities of tumour cells to survive through deregulated cell cycles and evade apoptosis are hallmarks of cancer. The ubiquitin-like proteins (UBL) proteasome system is important in regulating cell cycles via signaling proteins. Deregulation of the proteasomal system can lead to uncontrolled cell proliferation. The Skp, Cullin, F-box containing complex (SCF complex) is the predominant E3 ubiquitin ligase, and has diverse substrates. The ubiquitin ligase activity of the SCF complexes requires the conjugation of neural precursor cell expressed, developmentally down-regulated 8 (NEDD8) to cullin proteins...
December 2016: Oncology Letters
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