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https://www.readbyqxmd.com/read/29052230/omecamtiv-mercabil-and-blebbistatin-modulate-cardiac-contractility-by-perturbing-the-regulatory-state-of-the-myosin-filament
#1
Thomas Kampourakis, Xuemeng Zhang, Yin-Biao Sun, Malcolm Irving
Contraction of heart muscle is triggered by a transient rise in intracellular free calcium concentration linked to a change in the structure of the actin-containing thin filaments that allows the head or motor domains of myosin from the thick filaments to bind to them and induce filament sliding. It is becoming increasingly clear that cardiac contractility is also regulated through structural changes in the thick filaments, although the molecular mechanisms underlying thick filament regulation are still relatively poorly understood...
October 20, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29051728/exacerbation-of-brain-injury-by-post-stroke-exercise-is-contingent-upon-exercise-initiation-timing
#2
Fengwu Li, Xiaokun Geng, Hajra Khan, John T Pendy, Changya Peng, Xiaorong Li, Jose A Rafols, Yuchuan Ding
Accumulating evidence has demonstrated that post-stroke physical rehabilitation may reduce morbidity. The effectiveness of post-stroke exercise, however, appears to be contingent upon exercise initiation. This study assessed the hypothesis that very early exercise exacerbates brain injury, induces reactive oxygen species (ROS) generation, and promotes energy failure. A total of 230 adult male Sprague-Dawley rats were subjected to middle cerebral artery (MCA) occlusion for 2 h, and randomized into eight groups, including two sham injury control groups, three non-exercise and three exercise groups...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29046367/pkc%C3%AE-silencing-alleviates-saturated-fatty-acid-induced-er-stress%C3%A2-by-enhancing-serca-activity
#3
Shujie Lai, Yan Li, Yi Kuang, Hongli Cui, Yang Yang, Wenjing Sun, Kaijun Liu, Dongfeng Chen, Qixian Yan, Liangzhi Wen
Aim : Protein Kinase C δ (PKCδ) plays an important role in non-alcoholic fatty liver disease (NAFLD), however the mechanism remains unknown. This study explored the role of PKCδ in NAFLD development and investigated the relationships between PKCδ, calcium homeostasis and endoplasmic reticulum stress (ERS). Methods : Hepatic steatosis cell model was induced by palmitic acid (PA) in L02 cells. Lipid accretion was evaluated using Oil Red O staining and a triglyceride detection kit. PKCδ was down-regulated by siRNA...
October 18, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/29045918/cervical-cancer-cells-hela-response-to-photodynamic-therapy-using-a-zinc-phthalocyanine-photosensitizer
#4
Natasha Hodgkinson, Cherie Ann Kruger, Mpho Mokwena, Heidi Abrahamse
Cervical cancer is the most common gynecological malignancy worldwide, and the leading cause of cancer related deaths among females. Conventional treatment for early cervical cancer is radical hysterectomy. In locally advanced cancer the treatment of choice is concurrent chemo radiation. Although such treatment methods show promise, they do have adverse side effects. To minimize these effects, as well as prevent cancer re-occurrence, new treatment methods are being investigated. Photodynamic therapy (PDT) involves the selective uptake of a photosensitizer (PS) by cancer cells, illumination with light of an appropriate wavelength that triggers a photochemical reaction leading to the generation of reactive oxygen and subsequent tumor regression...
October 4, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/29045673/age-related-changes-in-the-mitochondria-of-human-mural-granulosa-cells
#5
Yifan Liu, Ming Han, Xiaoshuang Li, Hui Wang, Minyue Ma, Shihui Zhang, Yifan Guo, Shuling Wang, Yuanfen Wang, N Duan, Bing Xu, Jingwen Yin, Yuanqing Yao
STUDY QUESTION: What changes in the mitochondria of human mural granulosa cells (mGCs) with maternal aging? SUMMARY ANSWER: The mitochondrial membrane potential (MMP) and the ability of oxidative phosphorylation (OXPHOS) of mGCs declines with reproductive aging, accompanied with more abnormal mitochondria. WHAT IS KNOWN ALREADY: Mitochondria play an important role in the dialogue between the mGCs and oocytes. However, the underlying mechanism of mitochondrial dysfunction in mGCs in aging is still poorly understood...
October 17, 2017: Human Reproduction
https://www.readbyqxmd.com/read/29045028/biological-effects-of-er-yag-laser-irradiation-on-the-proliferation-of-primary-human-gingival-fibroblasts
#6
Sophannary Kong, Akira Aoki, Kengo Iwasaki, Koji Mizutani, Sayaka Katagiri, Tomonari Suda, Shizuko Ichinose, Mayumi Ogita, Verica Pavlic, Yuichi Izumi
We investigated the biological effects of Er:YAG laser (2,940-nm; DELight(®) , HOYA ConBio, USA) irradiation at fluences of 3.6, 4.2, 4.9, 6.3, 8.1, or 9.7 J cm(-2) at 20 or 30 Hz for 20 or 30 s on primary human gingival fibroblasts (HGFs). Irradiation at 6.3 J cm(-2) promoted maximal cell proliferation, determined by WST-8 assay and crystal violet staining, but was accompanied by lactate dehydrogenase release, on day 3 post-irradiation. Elevation of ATP level, Ki67 staining, and cyclin-A2 mRNA expression confirmed that Er:YAG affected the cell cycle and increased the number of proliferating cells...
October 17, 2017: Journal of Biophotonics
https://www.readbyqxmd.com/read/29042253/calcium-uptake-and-cytochrome-c-release-from-normal-and-ischemic-brain-mitochondria
#7
Alexander Andreyev, Pratistha Tamrakar, Robert E Rosenthal, Gary Fiskum
At abnormally elevated levels of intracellular Ca(2+), mitochondrial Ca(2+) uptake may compromise mitochondrial electron transport activities and trigger membrane permeability changes that allow for release of cytochrome c and other mitochondrial apoptotic proteins into the cytosol. In this study, a clinically relevant canine cardiac arrest model was used to assess the effects of global cerebral ischemia and reperfusion on mitochondrial Ca(2+) uptake capacity, Ca(2+) uptake-mediated inhibition of respiration, and Ca(2+)-induced cytochrome c release, as measured in vitro in a K(+)-based medium in the presence of Mg(2+), ATP, and NADH-linked oxidizable substrates...
October 14, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/29040977/gene-microarray-integrated-with-high-throughput-proteomics-for-the-discovery-of-transthyretin-in-rhabdomyolysis-induced-acute-kidney-injury
#8
Ou Li, Xiaodong Geng, Qian Ma, Weiwei Wang, Ran Liu, Zhong Yin, Siyang Wang, Guangyan Cai, Xiangmei Chen, Quan Hong
BACKGROUND/AIMS: Rhabdomyolysis, one of the leading causes of acute kidney injury (AKI), develops after trauma, drug toxicity, infections, burns, and physical exertion. The aim of this study was to investigate differences in gene and protein expression to elucidate the pathogenesis of rhabdomyolysis (RM)-induced AKI. METHODS: In this study, we used glycerol induced renal injury as a model of RM-induced AKI. Affymetrix U133 plus 2.0 microarrays were used to perform gene microarray analysis...
October 18, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29040533/hippocampal-phosphorylated-tau-induced-cognitive-decline-dendritic-spine-loss-and-mitochondrial-abnormalities-in-a-mouse-model-of-alzheimer-s-disease
#9
Ramesh Kandimalla, Maria Manczak, Xiangling Yin, Rui Wang, P Hemachandra Reddy
The purpose of our study was to understand the toxic effects of hippocampal phosphorylated tau in tau mice. Using rotarod and Morris Water Maze tests, immunoblotting & immunofluorescence, Golgi-cox staining and transmission electron microscopy, we assessed cognitive behavior, measured protein levels of mitochondrial dynamics, MAP2, total & phosphorylated tau, and quantified dendritic spines and mitochondrial number and length in 12-month-old tau mice with P301L mutation. Mitochondrial function was assessed by measuring the levels of H2O2, lipid peroxidation, cytochrome oxidase activity and mitochondrial ATP...
October 12, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29039506/hypothermic-machine-perfusion-ameliorates-inflammation-during-ischemia%C3%A2-reperfusion-injury-via-sirtuin%C3%A2-1%C3%A2-mediated-deacetylation-of-nuclear-factor%C3%A2-%C3%AE%C2%BAb-p65-in-rat-livers-donated-after-circulatory-death
#10
Cheng Zeng, Xiaoyan Hu, Weiyang He, Yanfeng Wang, Ling Li, Yan Xiong, Qifa Ye
Hypothermic machine perfusion (HMP) effectively reduces ischemia‑reperfusion injury (IRI) in livers donated after circulatory death (DCD) when compared with cold storage (CS). However, the underlying mechanisms remain unclear. The current study aimed to investigate the cellular mechanisms by which HMP ameliorates the inflammatory response during IRI. Adult male Sprague‑Dawley rat livers were exposed to 30 min of warm ischemia following cardiac arrest and preserved by CS or HMP for 3 h (n=3 per group)...
October 6, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29038055/serum-and-brain-purine-levels-in-an-experimental-systemic-infection-of-mice-by-cryptococcus-neoformans-purinergic-immunomodulatory-effects
#11
Maria Isabel de Azevedo, Aleksandro S Da Silva, Laerte Ferreiro, Pedro H Doleski, Alexandre A Tonin, Emerson A Casali, Cesar E J Moritz, Gabriel H Schirmbeck, Valesca V Cardoso, Mariana M Flores, Rafael Fighera, Janio M Santurio
The aim of this study was to evaluate the purine levels in serum and brains of mice experimentally infected by Cryptococcus neoformans. Twenty-four mice were divided into the following groups: a control group (n = 12; Group A) and an infection group with animals that were infected (n = 12; Group B) with a 0.3-mL intraperitoneal injection containing 1.7 × 10(7)C. neoformans cells. Blood and brains were collected on days 20 (n = 6 per group) and 50 (n = 6 per group) post-infection (PI). Histopathology and lung and brain cultures were performed to confirm fungal infection and tissue injuries...
October 13, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29036803/extracellular-atp-activates-enos-and-increases-intracellular-no-generation-in-red-blood-cells
#12
Pinar Ulker, Nur Özen, Günel Abdullayeva, Sadi Köksoy, Nazmi Yaraş, Filiz Basrali
BACKGROUND: It has been well documented that ATP activates NOS enzymes and causes increased NO production in several cell types. Although RBC known to possesses eNOS enzyme activity, it has not been investigated whether RBC eNOS could be induced by extracellular ATP. OBJECTIVE: The aim of the present study is to evaluate extracellular ATP mediated eNOS activation and NO production in RBC. METHODS: RBC packed were isolated from healthy volunteers and re-suspended in Hepes solution at a hematocrit of 0...
October 7, 2017: Clinical Hemorheology and Microcirculation
https://www.readbyqxmd.com/read/29036687/measuring-deaminated-nucleotide-surveillance-enzyme-itpa-activity-with-an-atp-releasing-nucleotide-chimera
#13
Debin Ji, Elena I Stepchenkova, Jian Cui, Miriam R Menezes, Youri I Pavlov, Eric T Kool
Nucleotide quality surveillance enzymes play important roles in human health, by detecting damaged molecules in the nucleotide pool and deactivating them before they are incorporated into chromosomal DNA or adversely affect metabolism. In particular, deamination of adenine moiety in (deoxy)nucleoside triphosphates, resulting in formation of (d)ITP, can be deleterious, leading to DNA damage, mutagenesis and other harmful cellular effects. The 21.5 kDa human enzyme that mitigates this damage by conversion of (d)ITP to monophosphate, ITPA, has been proposed as a possible therapeutic and diagnostic target for multiple diseases...
September 28, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29032333/glucagon-like-peptide-1-improves-%C3%AE-cell-dysfunction-by-suppressing-the-mir-27a-induced-downregulation-of-atp-binding-cassette-transporter-a1
#14
Yue Yao, Yi Xu, Wei Wang, Jinchao Zhang, Qiang Li
Lipotoxicity is considered one of the main causes of deterioration in β-cells function. Glucagon-like peptide-1 (GLP-1) has been revealed to protect and improve pancreatic β-cell function against lipotoxicity. However, the mechanism behind these is largely unknown. The aim of this study was to investigate the effects of GLP-1 on cholesterol-induced lipotoxicity in INS-1 cells and examine the underlying mechanisms. The cell viability was determined, and caspase-3 was used to assess the effects of GLP-1 on cholesterol-induced apoptosis...
October 12, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29031721/cdkal1-a-type-2-diabetes-susceptibility-gene-regulates-mitochondrial-function-in-adipose-tissue
#15
Colin J Palmer, Raphael J Bruckner, Joao A Paulo, Lawrence Kazak, Jonathan Z Long, Amir I Mina, Zhaoming Deng, Katherine B LeClair, Jessica A Hall, Shangyu Hong, Peter-James H Zushin, Kyle L Smith, Steven P Gygi, Susan Hagen, David E Cohen, Alexander S Banks
OBJECTIVES: Understanding how loci identified by genome wide association studies (GWAS) contribute to pathogenesis requires new mechanistic insights. Variants within CDKAL1 are strongly linked to an increased risk of developing type 2 diabetes and obesity. Investigations in mouse models have focused on the function of Cdkal1 as a tRNA(Lys) modifier and downstream effects of Cdkal1 loss on pro-insulin translational fidelity in pancreatic β-cells. However, Cdkal1 is broadly expressed in other metabolically relevant tissues, including adipose tissue...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29031563/gender-specific-association-of-desacylated-ghrelin-with-subclinical-atherosclerosis-in-the-metabolic-syndrome
#16
Michela Zanetti, Gianluca Gortan Cappellari, Annamaria Semolic, Ismet Burekovic, Maurizio Fonda, Luigi Cattin, Rocco Barazzoni
OBJECTIVE: Ghrelin, a gastric hormone with pleiotropic effects modulates vascular function and may influence atherosclerosis. Plasma ghrelin is reduced in the metabolic syndrome (MS), which is also characterized by early atherosclerosis. Ghrelin circulates in acylated (AG) and desacylated (DAG) forms. Their relative impact and that of gender on subclinical atherosclerosis in MS is unknown. AIM OF THE STUDY: To investigate potential associations of total, AG and DAG with carotid atherosclerosis and with gender in the MS...
October 11, 2017: Archives of Medical Research
https://www.readbyqxmd.com/read/29031076/synthesis-and-evaluation-of-new-pyridyl-pyrazinyl-thiourea-derivatives-neuroprotection-against-amyloid-%C3%AE-induced-toxicity
#17
Jung-Eun Park, Ahmed Elkamhawy, Ahmed H E Hassan, Ae Nim Pae, Jiyoun Lee, Sora Paik, Beoung-Geon Park, Eun Joo Roh
Herein, we report synthesis and evaluation of new twenty six small molecules against β amyloid (Aβ)-induced opening of mitochondrial permeability transition pore (mPTP) using JC-1 assay which measures the change of mitochondrial membrane potential (ΔΨm). The neuroprotective effect of seventeen compounds against Aβ-induced mPTP opening was superior to that of the standard Cyclosporin A (CsA). Fifteen derivatives eliciting increased green to red fluorescence percentage less than 40.0% were evaluated for their impact on ATP production, cell viability and neuroprotection against Aβ-induced neuronal cell death...
September 22, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29030562/astrocyte-calcium-waves-propagate-proximally-by-gap-junction-and-distally-by-extracellular-diffusion-of-atp-released-from-volume-regulated-anion-channels
#18
Yuki Fujii, Shohei Maekawa, Mitsuhiro Morita
Wave-like propagation of [Ca(2+)]i increases is a remarkable intercellular communication characteristic in astrocyte networks, intercalating neural circuits and vasculature. Mechanically-induced [Ca(2+)]i increases and their subsequent propagation to neighboring astrocytes in culture is a classical model of astrocyte calcium wave and is known to be mediated by gap junction and extracellular ATP, but the role of each pathway remains unclear. Pharmacologic analysis of time-dependent distribution of [Ca(2+)]i revealed three distinct [Ca(2+)]i increases, the largest being in stimulated cells independent of extracellular Ca(2+) and inositol 1,4,5-trisphosphate-induced Ca(2+) release...
October 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29027719/glioplasticity-in-irritable-bowel-syndrome
#19
N L Lilli, L Quénéhervé, S Haddara, C Brochard, P Aubert, M Rolli-Derkinderen, T Durand, P Naveilhan, J-B Hardouin, R De Giorgio, G Barbara, S Bruley des Varannes, E Coron, M Neunlist
BACKGROUND: Growing evidence indicates a wide array of cellular remodeling in the mucosal microenvironment during irritable bowel syndrome (IBS), which possibly contributes to pathophysiology and symptom generation. Here, we investigated whether enteric glial cells (EGC) may be altered, and which factors/mechanisms lead to these changes. METHODS: Colonic mucosal biopsies of IBS patients (13 IBS-Constipation [IBS-C]; 10 IBS-Diarrhea [IBS-D]; 11 IBS-Mixed [IBS-M]) and 24 healthy controls (HC) were analyzed...
October 13, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/29026074/structural-insights-into-the-competitive-inhibition-of-the-atp-gated-p2x-receptor-channel
#20
Go Kasuya, Toshiaki Yamaura, Xiao-Bo Ma, Ryoki Nakamura, Mizuki Takemoto, Hiromitsu Nagumo, Eiichi Tanaka, Naoshi Dohmae, Takanori Nakane, Ye Yu, Ryuichiro Ishitani, Osamu Matsuzaki, Motoyuki Hattori, Osamu Nureki
P2X receptors are non-selective cation channels gated by extracellular ATP, and the P2X7 receptor subtype plays a crucial role in the immune and nervous systems. Altered expression and dysfunctions of P2X7 receptors caused by genetic deletions, mutations, and polymorphic variations have been linked to various diseases, such as rheumatoid arthritis and hypertension. Despite the availability of crystal structures of P2X receptors, the mechanism of competitive antagonist action for P2X receptors remains controversial...
October 12, 2017: Nature Communications
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