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https://www.readbyqxmd.com/read/28449094/hepatic-tm6sf2-overexpression-affects-cellular-apob-trafficking-plasma-lipid-levels-hepatic-steatosis-and-atherosclerosis
#1
Nicole Ehrhardt, Michael E Doche, Shuang Chen, Hui Z Mao, Meghan T Walsh, Candy Bedoya, Maha Guindi, Weidong Xiong, Joseph Ignatius Irudayam, Jahangir Iqbal, Sebastien Fuchs, Samuel W French, M Mahmood Hussain, Moshe Arditi, Vaithilingaraja Arumugaswami, Miklós Péterfy
The human TM6SF2 gene has been implicated in plasma lipoprotein metabolism, alcoholic and non-alcoholic fatty liver disease and myocardial infarction in multiple genome-wide association studies. To investigate the role of Tm6sf2 in metabolic homeostasis, we generated mice with elevated expression using adeno-associated virus (AAV)-mediated gene delivery. Hepatic overexpression of mouse Tm6sf2 resulted in phenotypes previously observed in Tm6sf2-deficient mice including reduced plasma lipid levels, diminished hepatic TG secretion and increased hepatosteatosis...
April 25, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28448529/a-genome-wide-analysis-of-the-rna-guided-silencing-pathway-in-coffee-reveals-insights-into-its-regulatory-mechanisms
#2
Christiane Noronha Fernandes-Brum, Pâmela Marinho Rezende, Thales Henrique Cherubino Ribeiro, Raphael Ricon de Oliveira, Thaís Cunha de Sousa Cardoso, Laurence Rodrigues do Amaral, Matheus de Souza Gomes, Antonio Chalfun-Junior
microRNAs (miRNAs) are derived from self-complementary hairpin structures, while small-interfering RNAs (siRNAs) are derived from double-stranded RNA (dsRNA) or hairpin precursors. The core mechanism of sRNA production involves DICER-like (DCL) in processing the smallRNAs (sRNAs) and ARGONAUTE (AGO) as effectors of silencing, and siRNA biogenesis also involves action of RNA-Dependent RNA Polymerase (RDR), Pol IV and Pol V in biogenesis. Several other proteins interact with the core proteins to guide sRNA biogenesis, action, and turnover...
2017: PloS One
https://www.readbyqxmd.com/read/28447215/interplay-between-recombinant-hsp70-and-proteasomes-proteasome-activity-modulation-and-ubiquitin-independent-cleavage-of-hsp70
#3
Alexey V Morozov, Tatiana M Astakhova, David G Garbuz, George S Krasnov, Natalia V Bobkova, Olga G Zatsepina, Vadim L Karpov, Michail B Evgen'ev
The heat shock protein 70 (Hsp70, human HSPA1A) plays indispensable roles in cellular stress responses and protein quality control (PQC). In the framework of PQC, it cooperates with the ubiquitin-proteasome system (UPS) to clear damaged and dysfunctional proteins in the cell. Moreover, Hsp70 itself is rapidly degraded following the recovery from stress. It was demonstrated that its fast turnover is mediated via ubiquitination and subsequent degradation by the 26S proteasome. At the same time, the effect of Hsp70 on the functional state of proteasomes has been insufficiently investigated...
April 26, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28445477/mitochondrial-respiration-in-highly-aerobic-canines-in-the-non-raced-state-and-after-a-1600-km-sled-dog-race
#4
Benjamin Miller, Karyn Hamilton, Robert Boushel, Katherine Williamson, Verena Laner, Erich Gnaiger, Michael Davis
At the annual Iditarod Race, Alaskan Huskies repeatedly run for up to 8 hours at 16 km/h to complete 1600 km. We previously demonstrated high rates of mitochondrial protein synthesis in Alaskan Huskies, which we suspected allowed rapid remodeling of mitochondrial proteins in response to energetic stress. The purpose of this study was to examine mitochondrial respiration in permeabilized skeletal muscle fibers of Alaskan Huskies in the offseason (Non-raced) and following the 1600 km Iditarod Sled Dog Race (Raced)...
2017: PloS One
https://www.readbyqxmd.com/read/28443661/engineering-of-rumb-toward-a-green-catalyst-for-carbene-insertion-reactions
#5
Matthew W Wolf, David A Vargas, Nicolai Lehnert
The small, stable heme protein myoglobin (Mb) was modified through cofactor substitution and mutagenesis to develop a new catalyst for carbene transfer reactions. The native heme was removed from wild-type Mb and several Mb His64 mutants (H64D, H64A, H64V), and the resulting apoproteins were reconstituted with ruthenium mesoporphyrin IX (RuMpIX). The reconstituted proteins (RuMb) were characterized by UV-vis and circular dichroism spectroscopy and were used as catalysts for the N-H insertion of aniline derivatives and the cyclopropanation of styrene derivatives...
April 26, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28443117/seed-biology-updates-highlights-and-new-discoveries-in-seed-dormancy-and-germination-research
#6
REVIEW
Hiroyuki Nonogaki
An understanding of the biology of seeds has been greatly advanced in recent years. The progresses, particularly in the field of seed dormancy and germination research, have been made at a remarkable speed. Some of the possible epigenetic mechanisms, including an involvement of non-coding RNA, which were predicted for DELAY OF GERMINATION1 just a few years ago, have now been demonstrated with strong molecular and genetic evidence. Imprinting, or parent-of-origin-specific gene silencing/expression, which was characterized particularly for developing seeds, was also found in imbibed seeds and suggested for dormancy mechanisms...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28442264/mitochondrial-lon-protease-dependent-degradation-of-cytochrome-c-oxidase-subunits-under-hypoxia-and-myocardial-ischemia
#7
Naresh B V Sepuri, Rajesh Angireddy, Satish Srinivasan, Manti Guha, Joseph Spear, Bin Lu, Hindupur K Anandatheerthavarada, Carolyn K Suzuki, Narayan G Avadhani
The mitochondrial ATP dependent matrix protease, Lon, is involved in the maintenance of mitochondrial DNA nucleoids and degradation of abnormal or misfolded proteins. The Lon protease regulates mitochondrial Tfam (mitochondrial transcription factor A) level and thus modulates mitochondrial DNA (mtDNA) content. We have previously shown that hypoxic stress induces the PKA-dependent phosphorylation of cytochrome c oxidase (CcO) subunits I, IVi1, and Vb and a time-dependent reduction of these subunits in RAW 264...
April 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28441527/proteostasis-or-aging-let-the-chips-fall-where-they-may
#8
Robyn Branicky, Siegfried Hekimi
The conserved E3 ubiquitin ligase CHIP/CHN-1 contributes to proteostasis by ubiquitylating HSP70 and HSP90-interacting proteins. In a recent issue of Cell,Tawo et al. (2017) show that CHIP/CHN-1 also directly ubiquitylates the insulin receptor INSR/DAF-2 to regulate its turnover. These findings suggest an unexpected interpretation of the effects of altered proteostasis on survival.
April 24, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28440947/regulation-of-the-turnover-of-acc-synthases-by-phytohormones-and-heterodimerization-in-arabidopsis
#9
Han Yong Lee, Yi-Chun Chen, Joseph J Kieber, Gyeong Mee Yoon
Ethylene influences many aspects of plant growth and development. The biosynthesis of ethylene is highly regulated by a variety of internal and external cues. A key target of this regulation is 1-aminocyclopropane-1-carboxylic acid (ACC) synthases (ACS), generally the rate-limiting step in ethylene biosynthesis, which is regulated both transcriptionally and post-transcriptionally. Prior studies have demonstrated that cytokinin and brassinosteroid (BR) act as regulatory inputs to elevate ethylene biosynthesis by increasing the stability of ACS proteins...
April 25, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28440480/palmitate-impairs-angiogenesis-via-suppression-of-cathepsin-activity
#10
Jin Zhang, Ying Shan, Yong Li, Xinping Luo, Haiming Shi
Angiogenesis requires the interaction of multiple variable factors to promote endothelial cell adhesion, migration and survival. Palmitate, a free fatty acid, exhibits an anti‑angiogenic effect via interference with endothelial cell function, whereas cysteine proteases are important in protein turnover and are termed positive modulators of neovascularization. However, the association between these two factors regarding the regulation of human endothelial cell function remains to be elucidated. By using cell counting kit‑8, the Transwell method and an annexin V‑fluorescein isothiocyanate/propidium iodide apoptosis detection kit, the present study reported that high levels of palmitate result in a significant decrease in endothelial cell proliferation and invasion, and induced cell apoptosis; cathepsin L and S inhibitors may suppress palmitate‑induced apoptosis...
April 12, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28440186/the-double-roles-of-the-prostaglandin-e2-ep2-receptor-in-intracerebral-hemorrhage
#11
Xu Luo, Qiquan Zhu, Jie Zhang, Qin Huang, Zongyi Xie, Yuan Cheng
Intracerebral hemorrhage (ICH), a subtype of stroke, brings high morbidity and mortality to human beings. Multiple studies indicate that neuroinflammation, excitotoxicity, oxidative stress, cytotoxicity resulted from the degradation products of blood clot play vital roles in ICH-induced secondary brain injury, which contributes to deterioration of neurological outcome. Prostaglandin E2 (PGE2), a type of prostanoids commonly up-regulated in these progresses, is known to modulate numerous cellular and molecular processes and involve in various diseases, including ICH, cerebral ischemic, Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS) etc...
April 24, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28437460/an-aggregation-removal-model-for-the-formation-and-size-determination-of-post-synaptic-scaffold-domains
#12
Jonas Ranft, Leandro G Almeida, Pamela C Rodriguez, Antoine Triller, Vincent Hakim
The formation and stability of synapses are key questions in neuroscience. Post-synaptic domains have been classically conceived as resulting from local insertion and turnover of proteins at the synapse. However, insertion is likely to occur outside the post-synaptic domains and advances in single-molecule imaging have shown that proteins diffuse in the plane of the membrane prior to their accumulation at synapses. We quantitatively investigated this scenario using computer simulations and mathematical analysis, taking for definiteness the specific case of inhibitory synapse components, i...
April 24, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28436394/sarcomere-dysfunction-in-nemaline-myopathy
#13
Josine M de Winter, Coen A C Ottenheijm
Nemaline myopathy (NM) is among the most common non-dystrophic congenital myopathies (incidence 1:50.000). Hallmark features of NM are skeletal muscle weakness and the presence of nemaline bodies in the muscle fiber. The clinical phenotype of NM patients is quite diverse, ranging from neonatal death to normal lifespan with almost normal motor function. As the respiratory muscles are involved as well, severely affected patients are ventilator-dependent. The mechanisms underlying muscle weakness in NM are currently poorly understood...
April 19, 2017: Journal of Neuromuscular Diseases
https://www.readbyqxmd.com/read/28434889/depletion-of-tm6sf2-disturbs-membrane-lipid-composition-and-dynamics-in-huh7-hepatoma-cells
#14
Hanna Ruhanen, P A Nidhina Haridas, Eeva-Liisa Eskelinen, Ove Eriksson, Vesa M Olkkonen, Reijo Käkelä
A polymorphism of TM6SF2 associates with hepatic lipid accumulation and reduction of triacylglycerol (TAG) secretion, but the function of the encoded protein has remained enigmatic. We studied the effect of stable TM6SF2 knock-down on the lipid content and composition, mitochondrial fatty acid oxidation and organelle structure of HuH7 hepatoma cells. Knock-down of TM6SF2 resulted in intracellular accumulation of TAGs, cholesterol esters, phosphatidylcholine (PC) and phosphatidylethanolamine. In all of these lipid classes, polyunsaturated lipid species were significantly reduced while saturated and monounsaturated species increased their proportions...
April 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28432122/dual-regulation-of-stat1-and-stat3-by-the-tumor-suppressor-protein-pml-contributes-to-ifn%C3%AE-mediated-inhibition-of-angiogenesis
#15
Kuo-Sheng Hsu, Xuan Zhao, Xiwen Cheng, Dongyin Guan, Ganapati H Mahabeleshwar, Yu Liu, Ernest Borden, Mukesh K Jain, Hung-Ying Kao
IFNs are effective in inhibiting angiogenesis in preclinical models and in treating several angio-proliferative disorders. However, the detailed mechanisms of IFNα-mediated anti-angiogenesis are not completely understood. Stat1/2/3 and PML are IFNα downstream effectors and are pivotal regulators of angiogenesis. Here, we investigated PML's role in the regulation of Stat1/2/3 activity. In Pml knockout (KO) mice, ablation of Pml largely reduces IFNα angiostatic ability in Matrixgel plug assays. This suggested an essential role for PML in IFNα's anti-angiogenic function...
April 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28432079/regulation-of-microtubule-associated-motors-drives-intermediate-filament-network-polarization
#16
Cécile Leduc, Sandrine Etienne-Manneville
Intermediate filaments (IFs) are key players in the control of cell morphology and structure as well as in active processes such as cell polarization, migration, and mechanoresponses. However, the regulatory mechanisms controlling IF dynamics and organization in motile cells are still poorly understood. In this study, we investigate the mechanisms leading to the polarized rearrangement of the IF network along the polarity axis. Using photobleaching and photoconversion experiments in glial cells expressing vimentin, glial fibrillary acidic protein, and nestin, we show that the distribution of cytoplasmic IFs results from a continuous turnover based on the cooperation of an actin-dependent retrograde flow and anterograde and retrograde microtubule-dependent transports...
April 21, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28431247/the-ubiquitin-ligase-chip-integrates-proteostasis-and-aging-by-regulation-of-insulin-receptor-turnover
#17
Riga Tawo, Wojciech Pokrzywa, Éva Kevei, Melek E Akyuz, Vishnu Balaji, Svenja Adrian, Jörg Höhfeld, Thorsten Hoppe
Aging is attended by a progressive decline in protein homeostasis (proteostasis), aggravating the risk for protein aggregation diseases. To understand the coordination between proteome imbalance and longevity, we addressed the mechanistic role of the quality-control ubiquitin ligase CHIP, which is a key regulator of proteostasis. We observed that CHIP deficiency leads to increased levels of the insulin receptor (INSR) and reduced lifespan of worms and flies. The membrane-bound INSR regulates the insulin and IGF1 signaling (IIS) pathway and thereby defines metabolism and aging...
April 20, 2017: Cell
https://www.readbyqxmd.com/read/28430144/a-systems-biology-approach-using-transcriptomic-data-reveals-genes-and-pathways-in-porcine-skeletal-muscle-affected-by-dietary-lysine
#18
Taiji Wang, Jean M Feugang, Mark A Crenshaw, Naresh Regmi, John R Blanton, Shengfa F Liao
Nine crossbred finishing barrows (body weight 94.4 ± 6.7 kg) randomly assigned to three dietary treatments were used to investigate the effects of dietary lysine on muscle growth related metabolic and signaling pathways. Muscle samples were collected from the longissimus dorsi of individual pigs after feeding the lysine-deficient (4.30 g/kg), lysine-adequate (7.10 g/kg), or lysine-excess (9.80 g/kg) diet for five weeks, and the total RNA was extracted afterwards. Affymetrix Porcine Gene 1.0 ST Array was used to quantify the expression levels of 19,211 genes...
April 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28428740/protein-quality-control-by-molecular-chaperones-in-neurodegeneration
#19
REVIEW
Aaron Ciechanover, Yong Tae Kwon
Protein homeostasis (proteostasis) requires the timely degradation of misfolded proteins and their aggregates by protein quality control (PQC), of which molecular chaperones are an essential component. Compared with other cell types, PQC in neurons is particularly challenging because they have a unique cellular structure with long extensions. Making it worse, neurons are postmitotic, i.e., cannot dilute toxic substances by division, and, thus, are highly sensitive to misfolded proteins, especially as they age...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28428613/differential-regulation-of-pkd-isoforms-in-oxidative-stress-conditions-through-phosphorylation-of-a-conserved-tyr-in-the-p-1-loop
#20
Mathias Cobbaut, Rita Derua, Heike Döppler, Hua Jane Lou, Sandy Vandoninck, Peter Storz, Benjamin E Turk, Thomas Seufferlein, Etienne Waelkens, Veerle Janssens, Johan Van Lint
Protein kinases are essential molecules in life and their crucial function requires tight regulation. Many kinases are regulated via phosphorylation within their activation loop. This loop is embedded in the activation segment, which additionally contains the Mg(2+) binding loop and a P + 1 loop that is important in substrate binding. In this report, we identify Abl-mediated phosphorylation of a highly conserved Tyr residue in the P + 1 loop of protein kinase D2 (PKD2) during oxidative stress. Remarkably, we observed that the three human PKD isoforms display very different degrees of P + 1 loop Tyr phosphorylation and we identify one of the molecular determinants for this divergence...
April 20, 2017: Scientific Reports
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