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https://www.readbyqxmd.com/read/29772645/anticancer-activity-of-euplotin-c-isolated-from-the-marine-ciliate-euplotes-crassus-against-human-melanoma-cells
#1
Sara Carpi, Beatrice Polini, Giulio Poli, Gabriela Alcantara Barata, Stefano Fogli, Antonella Romanini, Tiziano Tuccinardi, Graziano Guella, Francesco Paolo Frontini, Paola Nieri, Graziano Di Giuseppe
Cutaneous melanoma is the most serious type of skin cancer, so new cytotoxic weapons against novel targets in melanoma are of great interest. Euplotin C (EC), a cytotoxic secondary metabolite of the marine ciliate Euplotes crassus , was evaluated in the present study on human cutaneous melanoma cells to explore its anti-melanoma activity and to gain more insight into its mechanism of action. EC exerted a marked cytotoxic effect against three different human melanoma cell lines (A375, 501Mel and MeWo) with a potency about 30-fold higher than that observed in non-cancer cells (HDFa cells)...
May 16, 2018: Marine Drugs
https://www.readbyqxmd.com/read/29760956/bh4-domain-peptides-derived-from-bcl-2-bcl-xl-as-novel-tools-against-acute-pancreatitis
#2
Tim Vervliet, Julia V Gerasimenko, Pawel E Ferdek, Monika A Jakubowska, Ole H Petersen, Oleg V Gerasimenko, Geert Bultynck
Biliary acute pancreatitis (AP) is a serious condition, which currently has no specific treatment. Taurolithocholic acid 3-sulfate (TLC-S) is one of the most potent bile acids causing cytosolic Ca2+ overload in pancreatic acinar cells (PACs), which results in premature activation of digestive enzymes and necrosis, hallmarks of AP. The inositol 1,4,5-trisphosphate receptor (IP3 R) and the ryanodine receptor (RyR) play major roles in intracellular Ca2+ signaling. Inhibition of these endoplasmic reticulum-located channels suppresses TLC-S-induced Ca2+ release and necrosis, decreasing the severity of AP...
2018: Cell Death Discovery
https://www.readbyqxmd.com/read/29760186/hypertrophic-cardiomyopathy-mutations-increase-myofilament-ca-2-buffering-alter-intracellular-ca-2-handling-and-stimulate-ca-2-dependent-signalling
#3
Paul Robinson, Xing Liu, Alexander Sparrow, Suketu Patel, Yin Hua Zhang, Barbara Casadei, Hugh Watkins, Charles S Redwood
Mutations in thin filament regulatory proteins that cause hypertrophic cardiomyopathy (HCM) increase myofilament Ca2+ -sensitivity. Mouse models exhibit increased Ca2+ buffering and arrhythmias, and we hypothesized that these changes are primary effects of the mutations (independent of compensatory changes) and that increased Ca2+ - buffering and altered Ca2+ -handling contribute to HCM pathogenesis via activation of Ca2+ -dependent signalling. Here, we determined the primary effects of HCM mutations on intracellular Ca2+ -handling and Ca2+ -dependent signalling in a model system possessing Ca2+ -handling mechanisms and contractile protein isoforms close to human in the absence of potentially confounding remodeling...
May 14, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29755362/the-interplay-of-rogue-and-clustered-ryanodine-receptors-regulates-ca-2-waves-in-cardiac-myocytes
#4
Xudong Chen, Yundi Feng, Yunlong Huo, Wenchang Tan
Ca2+ waves in cardiac myocytes can lead to arrhythmias owing to delayed after-depolarisations. Based on Ca2+ regulation from the junctional sarcoplasmic reticulum (JSR), a mathematical model was developed to investigate the interplay of clustered and rogue RyRs on Ca2+ waves. The model successfully reproduces Ca2+ waves in cardiac myocytes, which are in agreement with experimental results. A new wave propagation mode of "spark-diffusion-quark-spark" is put forward. It is found that rogue RyRs greatly increase the initiation of Ca2+ sparks, further contribute to the formation and propagation of Ca2+ waves when the free Ca2+ concentration in JSR lumen ([Ca2+ ]lumen ) is higher than a threshold value of 0...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29754802/intracellular-calcium-mobilization-is-required-for-sonic-hedgehog-signaling
#5
Dana Klatt Shaw, Derrick Gunther, Michael J Jurynec, Alexis A Chagovetz, Erin Ritchie, David Jonah Grunwald
Graded Shh signaling across fields of precursor cells coordinates patterns of gene expression, differentiation, and morphogenetic behavior as precursors form complex structures, such as the nervous system, the limbs, and craniofacial skeleton. Here we discover that intracellular calcium mobilization, a process tightly controlled and readily modulated, regulates the level of Shh-dependent gene expression in responding cells and affects the development of all Shh-dependent cell types in the zebrafish embryo. Reduced expression or modified activity of ryanodine receptor (RyR) intracellular calcium release channels shifted the allocation of Shh-dependent cell fates in the somitic muscle and neural tube...
May 8, 2018: Developmental Cell
https://www.readbyqxmd.com/read/29730765/control-of-neuronal-ryanodine-receptor-mediated-calcium-signaling-by-calsenilin
#6
Michael A Grillo, Stephanie L Grillo, Bryan C Gerdes, Jacob G Kraus, Peter Koulen
Calsenilin is a calcium ion (Ca2+ )-binding protein involved in regulating the intracellular concentration of Ca2+ , a second messenger that controls multiple cellular signaling pathways. The ryanodine receptor (RyR) amplifies Ca2+ signals entering the cytoplasm by releasing Ca2+ from endoplasmic reticulum (ER) stores, a process termed calcium-induced calcium release (CICR). Here, we describe a novel mechanism, in which calsenilin controls the activity of neuronal RyRs. We show calsenilin co-localized with RyR2 and 3 in the ER of mouse hippocampal and cortical neurons using immunocytochemistry...
May 5, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29727771/bifenthrin-causes-transcriptomic-alterations-in-mtor-and-ryanodine-receptor-dependent-signaling-and-delayed-hyperactivity-in-developing-zebrafish-danio-rerio
#7
Daniel F Frank, Galen W Miller, Danielle J Harvey, Susanne M Brander, Juergen Geist, Richard E Connon, Pamela J Lein
Over the last few decades, the pyrethroid insecticide bifenthrin has been increasingly employed for pest control in urban and agricultural areas, putting humans and wildlife at increased risk of exposure. Exposures to nanomolar (nM) concentrations of bifenthrin have recently been reported to alter calcium oscillations in rodent neurons. Neuronal calcium oscillations are influenced by ryanodine receptor (RyR) activity, which modulates calcium-dependent signaling cascades, including the mechanistic target of rapamycin (mTOR) signaling pathway...
April 18, 2018: Aquatic Toxicology
https://www.readbyqxmd.com/read/29719463/compound-k-induced-apoptosis-via-endoplasmic-reticulum-ca-2-release-through-ryanodine-receptor-in-human-lung-cancer-cells
#8
Dong-Hyun Shin, Dong-Gyu Leem, Ji-Sun Shin, Joo-Il Kim, Kyung-Tack Kim, Sang Yoon Choi, Myung-Hee Lee, Jung-Hye Choi, Kyung-Tae Lee
Background: Extended endoplasmic reticulum (ER) stress may initiate apoptotic pathways in cancer cells, and ER stress has been reported to possibly increase tumor death in cancer therapy. We previously reported that caspase-8 played an important role in compound K-induced apoptosis via activation of caspase-3 directly or indirectly through Bid cleavage, cytochrome c release, and caspase-9 activation in HL-60 human leukemia cells. The mechanisms leading to apoptosis in A549 and SK-MES-1 human lung cancer cells and the role of ER stress have not yet been understood...
April 2018: Journal of Ginseng Research
https://www.readbyqxmd.com/read/29718870/ctla-4-methylation-regulates-the-pathogenesis-of-myasthenia-gravis-and-the-expression-of-related-cytokines
#9
Ti-Kun Fang, Cheng-Jun Yan, Juan Du
BACKGROUND: Myasthenia gravis (MG) is a progressive autoimmune disease that occurs as a result of the failure of neuromuscular transmission and is characterized by muscle weakness. There has been evidence on the correlations between the genetic predisposition of cytotoxic T lymphocyte and the antigen-4 (CTLA-4) and MG. Thus, the present study was conducted to study is designed to examine the effects of CTLA-4 methylation on the pathogenesis of MG and the expressions of related cytokines...
May 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29715473/stabilization-of-ca-2-signaling-in-cardiac-muscle-by-stimulation-of-serca
#10
Miguel Fernandez-Tenorio, Ernst Niggli
AIMS: In cardiac muscle, phosphorylation of the RyRs is proposed to increase their Ca2+ sensitivity. This mechanism could be arrhythmogenic via facilitation of spontaneous Ca2+ waves. Surprisingly, the level of Ca2+ inside the SR needed to initiate such waves has been reported to increase upon β-adrenergic stimulation, an observation which cannot be easily reconciled with elevated Ca2+ sensitivity of the RyRs. We tested the hypothesis that this change of Ca2+ wave threshold could occur indirectly, subsequent to SERCA stimulation...
April 30, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29678654/4tm-trpm8-channels-are-new-gatekeepers-of-the-er-mitochondria-ca-2-transfer
#11
Gabriel Bidaux, Dmitri Gordienko, George Shapovalov, Valerio Farfariello, Anne-Sophie Borowiec, Oksana Iamshanova, Loic Lemonnier, Maxime Gueguinou, Roseline Guibon, Gaelle Fromont, Mélanie Paillard, Yves Gouriou, Christophe Chouabe, Etienne Dewailly, Dimitra Gkika, Pilar López-Alvarado, J Carlos Menéndez, Laurent Héliot, Christian Slomianny, Natalia Prevarskaya
Calcium (Ca2+ ) release from the endoplasmic reticulum plays an important role in many cell-fate defining cellular processes. Traditionally, this Ca2+ release was associated with the ER Ca2+ release channels, inositol 1,4,5‑triphosphate receptor (IP3 R) and ryanodine receptor (RyR). Lately, however, other calcium conductances have been found to be intracellularly localized and to participate in cell fate regulation. Nonetheless, molecular identity and functional properties of the ER Ca2+ release mechanisms associated with multiple diseases, e...
April 17, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29676187/decrease-of-ryr2-in-the-prion-infected-cell-line-and-in-the-brains-of-the-scrapie-infected-mice-models-and-the-patients-of-human-prion-diseases
#12
Qi Shi, Jian-Le Li, Yue Ma, Li-Ping Gao, Kang Xiao, Jing Wang, Wei Zhou, Cao Chen, Yan-Jun Guo, Xiao-Ping Dong
The levels of ryanodine receptors (RyRs) are usually increased in the brains of human Alzheimer disease (AD) and AD animal models. To evaluate the underlying alteration of brain RyRs in prion disease, scrapie infected cell line SMB-S15 and its infected mice were tested. RyR2 specific Western blots revealed markedly decreased RyR2 levels both in the cells and in the brains of infected mice. Assays of the brain samples of other scrapie (agents 139A and ME7) infected mice collected at different time-points during incubation period showed time-dependent decreases of RyR2...
April 20, 2018: Prion
https://www.readbyqxmd.com/read/29674523/efficient-high-throughput-screening-by-er-ca-2-measurement-to-identify-inhibitors-of-ryanodine-receptor-ca2-release-channels
#13
Takashi Murayama, Nagomi Kurebayashi, Mari Ikegami-Yuasa, Shuichi Mori, Yukina Suzuki, Ryunosuke Akima, Haruo Ogawa, Junji Suzuki, Kazunori Kanemaru, Hideto Oyamada, Yuji Kiuchi, Masamitsu Iino, Hiroyuki Kagechika, Takashi Sakurai
Genetic mutations in ryanodine receptors (RyRs), Ca2+-release channels in the sarcoplasmic reticulum essential for muscle contractions, cause various skeletal muscle and cardiac diseases. Because the main underlying mechanism of the pathogenesis is overactive Ca2+ release by gain-of-function of the RyR channel, inhibition of RyRs is expected to be a promising treatment for these diseases. Here, to identify inhibitors specific to skeletal muscle type 1 RyR (RyR1), we developed a novel high-throughput screening (HTS) platform using time-lapse fluorescence measurement of Ca2+ concentrations in the endoplasmic reticulum (ER) ([Ca2+]ER)...
April 19, 2018: Molecular Pharmacology
https://www.readbyqxmd.com/read/29668881/hyperactive-ryanodine-receptors-in-human-heart-failure-and-ischemic-cardiomyopathy-reside-outside-of-couplons
#14
Eef Dries, Demetrio J Santiago, Guillaume Gilbert, Ilse Lenaerts, Bert Vandenberk, Chandan K Nagaraju, Daniel M Johnson, Patricia Holemans, H Llewelyn Roderick, Niall Macquaide, Piet Claus, Karin R Sipido
Aims: In ventricular myocytes from humans and large mammals, the transverse and axial tubular system (TATS) network is less extensive than in rodents with consequently a greater proportion of ryanodine receptors (RyRs) not coupled to this membrane system. TATS remodeling in heart failure (HF) and after myocardial infarction (MI) increases the fraction of non-coupled RyR. Here we investigate whether this remodeling alters the activity of coupled and non-coupled RyR sub-populations through changes in local signaling...
April 14, 2018: Cardiovascular Research
https://www.readbyqxmd.com/read/29653363/trapidil-improves-hemodynamic-echocardiographic-and-redox-state-parameters-of-right-ventricle-in-monocrotaline-induced-pulmonary-arterial-hypertension-model
#15
Patrick Türck, Denise Santos Lacerda, Cristina Campos Carraro, Bruna Gazzi de Lima-Seolin, Rayane Brinck Teixeira, Jéssica Hellen Poletto Bonetto, Rafael Colombo, Paulo Cavalheiro Schenkel, Adriane Belló-Klein, Alex Sander da Rosa Araujo
BACKGROUND: Pulmonary arterial hypertension is a disease characterized by increased pulmonary vascular resistance and redox imbalance, leading to failure of right ventricle. Trapidil has been described to improve the redox balance and cardiac conditions. HYPOTHESIS: Trapidil can improve the redox balance and contribute to functional improvements of the RV in PAH. METHODS AND RESULTS: Male, 5week-old Wistar rats were divided into four groups: Control, Control + Trapidil, Monocrotaline and Monocrotaline + Trapidil...
April 10, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29626986/molecular-characterization-and-expression-profiling-of-ryanodine-receptor-gene-in-the-pink-stem-borer-sesamia-inferens-walker
#16
Shun-Fan Wu, Dan-Dan Zhao, Jing-Mei Huang, Si-Qi Zhao, Li-Qi Zhou, Cong-Fen Gao
The susceptibilities of three field populations of pink stem borer (PSB), Sesamia inferens (walker) to diamide insecticides, chlorantraniliprole and flubendiamide, were evaluated in this study. The results showed that these PSB field populations were still sensitive to the two diamide insecticides after many years of exposure. To further understand PSB and diamide insecticide, the full-length ryanodine receptor (RyR) cDNA (named as SiRyR), the molecular target of diamide insecticides was cloned from PSB and characterized...
April 2018: Pesticide Biochemistry and Physiology
https://www.readbyqxmd.com/read/29609929/red-yeast-rice-ryr-supplementation-in-patients-treated-with-second-generation-antipsychotics
#17
Antonio Bruno, Gianluca Pandolfo, Manuela Crucitti, Giulia Maria Troili, Edoardo Spina, Rocco Antonio Zoccali, Maria Rosaria Anna Muscatello
OBJECTIVE: Second-generation antipsychotics (SGAs) have a negative impact on metabolic syndrome (MetS) risk factors for their effects on body weight and on metabolic parameters. Statins are widely used in the treatment of dyslipidemia; less is known on the ability of statins to treat SGAs-induced dyslipidemia, and nutraceutical approaches may represent promising strategies in SGAs-treated patients. Red Yeast Rice (RYR), the fermented product of the Aspergillaceae mold Monascus purpureus (red yeast) grown on white rice, has been shown to have a cholesterol-lowering effect which can be ascribed to monacolin K, although other active compounds may play a role management of hyperlipidemia...
April 2018: Complementary Therapies in Medicine
https://www.readbyqxmd.com/read/29600763/ryanodine-receptors-for-drugs-and-insecticides-an-overview
#18
Hui Xu, Zhiqiang Sun
Ryanodine receptors (RyRs) are calcium channels located on the endo(sarco)plasmic reticulum of muscle cells and neurons. They regulate release of stored intracellular calcium and play a critical role in muscle contraction. The N-terminal part of these receptors accounts for roughly 80% and contains the binding sites for diverse RyRs modulators. The C-terminal domain contains the transmembrane region. Ryanodine, a plant alkaloid, has been investigated extensively as a potential pest control agent but no selectivity between mammalians and insect pests...
March 29, 2018: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/29593014/ryanodine-receptor-calcium-leak-in-circulating-b-lymphocytes-as-a-biomarker-in-heart-failure
#19
Alexander Kushnir, Gaetano Santulli, Steven R Reiken, Ellie Coromilas, Sarah J Godfrey, Danielle L Brunjes, Paolo C Colombo, Melana Yuzefpolskaya, Seth I Sokol, Richard N Kitsis, Andrew R Marks
Background -Advances in congestive heart failure (CHF) management depend on biomarkers for monitoring disease progression and therapeutic response. During systole, intracellular Ca2+ is released from the sarcoplasmic reticulum (SR) into the cytoplasm through type 2 ryanodine receptor/Ca2+ release channels (RyR2). In CHF, chronically elevated circulating catecholamine levels cause pathologic remodeling of RyR2 resulting in diastolic SR Ca2+ leak, and decreased myocardial contractility. Similarly, skeletal muscle contraction requires SR Ca2+ release through type-1 ryanodine receptors (RyR1), and chronically elevated catecholamine levels in CHF cause RyR1 mediated SR Ca2+ leak, contributing to myopathy and weakness...
March 28, 2018: Circulation
https://www.readbyqxmd.com/read/29582393/adverse-events-to-food-supplements-containing-red-yeast-rice-comparative-analysis-of-faers-and-caers-reporting-systems
#20
Emanuel Raschi, Anna Girardi, Elisabetta Poluzzi, Emanuele Forcesi, Francesca Menniti-Ippolito, Gabriela Mazzanti, Fabrizio De Ponti
INTRODUCTION: Food supplements containing red yeast rice (RYR) are proposed as an alternative in statin-intolerant patients, although they actually contain natural statin(s) and their safety in clinical practice is still incompletely characterized. We described and compared adverse events (AEs) associated with RYR products submitted to reporting systems maintained by the Food and Drug Administration (FDA), with a focus on liver and muscular events. METHODS: We extracted RYR-related AEs from the FDA Adverse Event Reporting System (FAERS) [first quarter (Q1)-2004 to Q2-2016], a drug-based archive, and the Center for Food Safety and Applied Nutrition Adverse Event Reporting System (CAERS) (Q1-2004 to Q1-2017)...
March 26, 2018: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
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