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https://www.readbyqxmd.com/read/29166700/dlp1-dependent-mitochondrial-fragmentation-and-redistribution-mediate-prion-associated-mitochondrial-dysfunction-and-neuronal-death
#1
Chaosi Li, Di Wang, Wei Wu, Wei Yang, Syed Zahid Ali Shah, Ying Zhao, Yuhan Duan, Lu Wang, Xiangmei Zhou, Deming Zhao, Lifeng Yang
Mitochondrial malfunction is a universal and critical step in the pathogenesis of many neurodegenerative diseases including prion diseases. Dynamin-like protein 1 (DLP1) is one of the key regulators of mitochondrial fission. In this study, we investigated the role of DLP1 in mitochondrial fragmentation and dysfunction in neurons using in vitro and in vivo prion disease models. Mitochondria became fragmented and redistributed from axons to soma, correlated with increased mitochondrial DLP1 expression in murine primary neurons (N2a cells) treated with the prion peptide PrP(106-126) in vitro as well as in prion strain-infected hamster brain in vivo...
November 22, 2017: Aging Cell
https://www.readbyqxmd.com/read/29166037/adenosine-triphosphate-diffusion-through-poly-ethylene-glycol-diacrylate-hydrogels-can-be-tuned-by-cross-link-density-as-measured-by-pfg-nmr
#2
Günter Majer, Alexander Southan
The diffusion of small molecules through hydrogels is of great importance for many applications. Especially in biological contexts, the diffusion of nutrients through hydrogel networks defines whether cells can survive inside the hydrogel or not. In this contribution, hydrogels based on poly(ethylene glycol) diacrylate with mesh sizes ranging from ξ = 1.1 to 12.9 nm are prepared using polymers with number-average molecular weights between Mn = 700 and 8000 g/mol. Precise measurements of diffusion coefficients D of adenosine triphosphate (ATP), an important energy carrier in biological systems, in these hydrogels are performed by pulsed field gradient nuclear magnetic resonance...
June 14, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/29165759/transient-receptor-potential-melastatin-4-cation-channel-in-pediatric-heart-block
#3
J Tian, X-J An, M-Y Fu
Progressive cardiac conduction disease (PCCD) is a common pediatric heart conduction disorder. It is an autosomal inheritance of rare mutations, which leads to familial cases of PCCD. In these cases, the His-Purkinje system's conductive capacity is progressively deranged, involving either right or left bundle branch block. Also, QRS complexes display widening is an important characteristic that culminates in complete AV block, syncope, and sudden death. Mutations in TRPM4 gene that encodes for transient receptor potential melastatin 4 have recently been reported to cause familial cases of PCCD and heart block...
October 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29165676/structure-of-mycobacterial-3-to-5-rna-dna-helicase-lhr-bound-to-a-ssdna-tracking-strand-highlights-distinctive-features-of-a-novel-family-of-bacterial-helicases
#4
Anam Ejaz, Heather Ordonez, Agata Jacewicz, Ryan Ferrao, Stewart Shuman
Mycobacterial Lhr is a DNA damage-inducible superfamily 2 helicase that uses adenosine triphosphate (ATP) hydrolysis to drive unidirectional 3'-to-5' translocation along single-stranded DNA (ssDNA) and to unwind RNA:DNA duplexes en route. ATPase, translocase and helicase activities are encompassed within the N-terminal 856-amino acid segment. The crystal structure of Lhr-(1-856) in complex with AMPPNP•Mg2+ and ssDNA defines a new helicase family. The enzyme comprises two N-terminal RecA-like modules, a winged helix (WH) domain and a unique C-terminal domain...
November 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29165439/proteomic-signatures-differentiating-bacillus-anthracis-sterne-sporulation-on-soil-relative-to-laboratory-media
#5
D S Wunschel, J R Hutchison, B L Deatherage Kaiser, E D Merkley, B M Hess, A Lin, M G Warner
The process of sporulation is vital for the stability and infectious cycle of Bacillus anthracis. The spore is the infectious form of the organism and therefore relevant to biodefense. While the morphological and molecular events occurring during sporulation have been well studied, the influence of growth medium and temperature on the proteins expressed in sporulated cultures is not well understood. Understanding the features of B. anthracis sporulation specific to natural vs. laboratory production will address an important question in microbial forensics...
November 22, 2017: Analyst
https://www.readbyqxmd.com/read/29165327/effects-of-dl-3-n-butylphthalide-on-cerebral-ischemia-infarction-in-rat-model-by-mass-spectrometry-imaging
#6
Run-Zhe Liu, Chao-Xin Fan, Zhi-Lin Zhang, Xin Zhao, Yi Sun, Hui-Hui Liu, Zong-Xiu Nie, Xiao-Ping Pu
Dl-3-n-butylphthalide (NBP) is a drug that is used in the treatment of ischaemic stroke. However, to the best of our knowledge, there are no systematic studies investigating the effects of dl-3-n-butylphtalide on the brain metabolism of small molecules. In this study, we first investigated the effects of dl-3-n-butylphthalide on the spatial distribution of small molecules in the brains of rats with permanent middle cerebral artery occlusion (pMCAO) using matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) imaging...
November 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29165246/regulatory-coiled-coil-domains-promote-head-to-head-assemblies-of-aaa-chaperones-essential-for-tunable-activity-control
#7
Marta Carroni, Kamila B Franke, Michael Maurer, Jasmin Jäger, Ingo Hantke, Felix Gloge, Daniela Linder, Sebastian Gremer, Kürşad Turgay, Bernd Bukau, Axel Mogk
Ring-forming AAA+ chaperones exert ATP-fueled substrate unfolding by threading through a central pore. This activity is potentially harmful requiring mechanisms for tight repression and substrate-specific activation. The AAA+ chaperone ClpC with the peptidase ClpP forms a bacterial protease essential to virulence and stress resistance. The adaptor MecA activates ClpC by targeting substrates and stimulating ClpC ATPase activity. We show how ClpC is repressed in its ground state by determining ClpC cryo-EM structures with and without MecA...
November 22, 2017: ELife
https://www.readbyqxmd.com/read/29165244/the-aaa-atpase-vps4-binds-escrt-iii-substrates-through-a-repeating-array-of-dipeptide-binding-pockets
#8
Han Han, Nicole Monroe, Wesley I Sundquist, Peter S Shen, Christopher P Hill
The hexameric AAA ATPase Vps4 drives membrane fission by remodeling and disassembling ESCRT-III filaments. Building upon our earlier 4.3 Å resolution cryo-EM structure (Monroe, Han et al. 2017), we now report a 3.2 Å structure of Vps4 bound to an ESCRT-III peptide substrate. The new structure reveals that the peptide approximates a b-strand conformation whose helical symmetry matches that of the five Vps4 subunits it contacts directly. Adjacent Vps4 subunits make equivalent interactions with successive substrate dipeptides through two distinct classes of side chain binding pockets formed primarily by Vps4 pore loop 1...
November 22, 2017: ELife
https://www.readbyqxmd.com/read/29165233/the-sec-system-protein-export-in-escherichia-coli
#9
Jennine M Crane, Linda L Randall
In Escherichia coli, proteins found in the periplasm or the outer membrane are exported from the cytoplasm by the general secretory, Sec, system before they acquire stably folded structure. This dynamic process involves intricate interactions among cytoplasmic and membrane proteins, both peripheral and integral, as well as lipids. In vivo, both ATP hydrolysis and proton motive force are required. Here, we review the Sec system from the inception of the field through early 2016, including biochemical, genetic, and structural data...
November 2017: EcoSal Plus
https://www.readbyqxmd.com/read/29165089/a-novel-method-to-synthesize-phosphocreatine-and-phosphocreatine-prodrugs
#10
Maria Arkel, Patrizia Garbati, Annalisa Salis, Gianluca Damonte, Nara Liessi, Enrico Adriano, Umberto Benatti, Maurizio Balestrino, Enrico Millo
Background Adenosine triphosphate (ATP) is the energy currency of the body; it takes part in various and indispensable metabolic processes for the maintenance of cell homeostasis, degrading to its hydrolysis product, adenosine diphosphate (ADP). Efficient ways to restore ATP are therefore necessary in the cells. When the cell lacks energy due to ischemic conditions or high ATP demand, phosphocreatine gives its phosphate group to ADP that converts to ATP, in a reaction catalyzed by the enzyme creatine kinase...
November 20, 2017: Medicinal Chemistry
https://www.readbyqxmd.com/read/29165041/akt-mediated-phosphorylation-of-atg4b-impairs-mitochondrial-activity-and-enhances-the-warburg-effect-in-hepatocellular-carcinoma-cells
#11
Zhenhong Ni, Jintao He, Yaran Wu, Changjiang Hu, Xufang Dai, Xiaojing Yan, Bo Li, Xinzhe Li, Haojun Xiong, Yuming Li, Song Li, Liang Xu, Yongsheng Li, Jiqin Lian, Fengtian He
Phosphorylation is a major type of post-translational modification, which can influence the cellular physiological function. ATG4B, a key macroautophagy/autophagy-related protein, has a potential effect on the survival of tumor cells. However, it is still unknown as to the role of ATG4B phosphorylation in cancers. In this study, we identified a novel phosphorylation site at Ser34 of ATG4B induced by AKT in HCC cells. The phosphorylation of ATG4B at Ser34 had little effect on autophagic flux, but promoted the Warburg effect including the increase of L-lactate production and glucose consumption, and the decrease of oxygen consumption in HCC cells...
November 22, 2017: Autophagy
https://www.readbyqxmd.com/read/29164889/comparison-of-quantitative-mass-spectrometry-platforms-for-monitoring-kinase-atp-probe-uptake-in-lung-cancer
#12
Melissa A Hoffman, Bin Fang, Eric B Haura, Uwe Rix, John M Koomen
Recent developments in instrumentation and bioinformatics have led to new quantitative mass spectrometry platforms including LC-MS/MS with data-independent acquisition (DIA) and targeted analysis using parallel reaction monitoring mass spectrometry (LC-PRM), which provide alternatives to well-established methods, such as LC-MS/MS with data-dependent acquisition (DDA) and targeted analysis using multiple reaction monitoring mass spectrometry (LC-MRM). These tools have been used to identify signaling perturbations in lung cancers and other malignancies, supporting the development of effective kinase inhibitors and, more recently, providing insights into therapeutic resistance mechanisms and drug repurposing opportunities...
November 22, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/29164820/dual-ppar%C3%AE-%C3%AE-agonist-saroglitazar-improves-liver-histopathology-and-biochemistry-in-experimental-nash-models
#13
Mukul R Jain, Suresh R Giri, Bibhuti Bhoi, Chitrang Trivedi, Akshyaya Rath, Rohan Rathod, Ramchandra Ranvir, Shekhar Kadam, Hiren Patel, Prabodha Swain, Sib Sankar Roy, Nabanita Das, Eshani Karmakar, Walter Wahli, Pankaj R Patel
BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are common clinico-pathological conditions that affect millions of patients worldwide. In this study, the efficacy of saroglitazar, a novel PPARα/γ agonist, was assessed in models of NAFLD/NASH. METHODS & RESULTS: HepG2 cells treated with palmitic acid (PA;0.75 mM) showed decreased expression of various antioxidant biomarkers (SOD1, SOD2, glutathione peroxidase and catalase) and increased expression of inflammatory markers (TNFα,IL1β and IL6)...
November 21, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/29164525/heat-shock-factor-4-regulates-the-expression-of-hsp25-and-alpha-b-crystallin-by-associating-with-dexd-h-box-rna-helicase-uap56
#14
Xiukun Cui, Wenxiu Han, Jing Li, Riping Feng, Zheng Zhou, JiuLi Han, Mengyuan Li, Shuangfeng Wang, Wanting Zhang, Qin Lei, Jun Zhang, Yutiao Liu, Yanzhong Hu
Heat shock factor 4 controls the transcription of small heat shock proteins (e.g., HSP25, alpha B-cyrstallin, and r-crystallin), that play important roles in modulating lens proteostasis. However, the molecular mechanism underlying HSF4-mediated transcription is still unclear. Using yeast two hybrid, we found that HSF4 interacts with the ATP-dependent DEXD/H-box RNA helicase UAP56, and their interaction in lens epithelial cell line was further confirmed by GST-pull down assay. UAP56 is a vital regulator of pre-mRNA splicing and mature mRNA nuclear export...
November 21, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/29164506/enzymatic-production-of-glutathione-coupling-with-an-atp-regeneration-system-based-on-polyphosphate-kinase
#15
Hao Cao, Chengcheng Li, Jing Zhao, Fang Wang, Tianwei Tan, Luo Liu
Glutathione (GSH) is an important reducing agent in the living cells. It is synthesized by a two-step reaction and requires two molecules of adenosine triphosphate (ATP) for one molecule GSH. The enzymatic cascade reaction in vitro is a promising approach to achieve a high titer and limit side reactions; although, a cost-effective phosphate donor for ATP regeneration is required. Triphosphate (PolyP(3)), tetraphosphate (PolyP(4)), and hexametaphosphate (PolyP(6)) were investigated in this study. Triphosphate inhibited the bifunctional GSH synthetase (GshF) from Streptococcus agalactiae, while no significant inhibition was observed by adding hexametaphosphate...
November 21, 2017: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/29164469/antibiotic-anisomycin-induces-cell-cycle-arrest-and-apoptosis-through-inhibiting-mitochondrial-biogenesis-in-osteosarcoma
#16
Chuanhua Cao, Haiying Yu, Feng Wu, Huixiong Qi, Jingbo He
The anti-cancer activities of antibiotic anisomycin have been demonstrated in kidney, colon and ovarian cancers whereas its underlying mechanisms are not well elucidated. In this work, we investigated whether anisomycin is effective in sensitizes osteosarcoma cell response to chemotherapy. We show that anisomycin inhibits proliferation via inducing osteosarcoma cell arrest at G2/M phase, accompanied by the increased levels of mitotic marker cyclin B and the decreased levels of Rb and E2F-1. Anisomycin also induces apoptosis in a caspase-dependent manner in osteosarcoma cells...
November 21, 2017: Journal of Bioenergetics and Biomembranes
https://www.readbyqxmd.com/read/29164451/the-potential-of-p2x7-receptors-as-a-therapeutic-target-including-inflammation-and-tumour-progression
#17
REVIEW
Geoffrey Burnstock, Gillian E Knight
Seven P2X ion channel nucleotide receptor subtypes have been cloned and characterised. P2X7 receptors (P2X7R) are unusual in that there are extra amino acids in the intracellular C terminus. Low concentrations of ATP open cation channels sometimes leading to cell proliferation, whereas high concentrations of ATP open large pores that release inflammatory cytokines and can lead to apoptotic cell death. Since many diseases involve inflammation and immune responses, and the P2X7R regulates inflammation, there has been recent interest in the pathophysiological roles of P2X7R and the potential of P2X7R antagonists to treat a variety of diseases...
November 21, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/29164394/combination-of-nad-and-nadph-offers-greater-neuroprotection-in-ischemic-stroke-models-by-relieving-metabolic-stress
#18
Qiao Huang, Meiling Sun, Mei Li, Dingmei Zhang, Feng Han, Jun Chao Wu, Kohji Fukunaga, Zhong Chen, Zheng-Hong Qin
Both reduced nicotinamide adenine dinucleotide phosphate (NADPH) and β-nicotinamide adenine dinucleotide hydrate (NAD(+)) have been reported to have potent neuroprotective effects against ischemic neuronal injury. Both NADPH and NAD(+) are essential cofactors for anti-oxidation and cellular energy metabolism. We investigated if combined NADPH and NAD(+) could offer better neuroprotective effects on cellular and animal models of ischemic stroke. In vitro studies with primary cultured neurons demonstrated that NAD(+) was effective in protecting neurons against oxygen-glucose deprivation/reoxygenation (OGD/R) injury when given during the early time period of reoxygenation...
November 21, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29163775/loss-of-sun2-promotes-the-progression-of-prostate-cancer-by-regulating-fatty-acid-oxidation
#19
Cheng Yajun, Ye Chen, Li Xiaosa, Wang Xiao, Chen Jia, Wang Zhong, Xu Bin
The role of Sun2 has been described by previous studies in various types of cancers, including breast cancer and lung cancer. However, its role and potential molecular mechanism in the progression of prostate cancer have not been fully elucidated. In the present study, we found that Sun2 expression was reduced in prostate cancer tissues compared with paired normal tissues, and that low expression of Sun2 was significantly correlated with Higher Gleason scores, postoperative T stage (pT), Lymph nodal invasion and Clinical pathological stages...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163573/mitochondrial-uncoupling-protein-1-overexpression-increases-yield-in-nicotiana-tabacum-under-drought-stress-by-improving-source-and-sink-metabolism
#20
Pedro Barreto, Juliana E C T Yassitepe, Zoe A Wilson, Paulo Arruda
Mitochondrial uncoupling proteins (UCPs) sustain mitochondrial respiration independent of intracellular ATP concentration. Uncoupled respiration is particularly beneficial under stress conditions, during which both photosynthesis and respiration may be impaired. Sustaining carbon fixation during the reproductive phase is essential for plants to develop viable pollen grains and for seed setting. Here, we examined whether UCP1 overexpression (UCP1-oe) would help tobacco plants cope with drought stress during reproductive development...
2017: Frontiers in Plant Science
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