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https://www.readbyqxmd.com/read/29337220/botaf-a-new-buthus-occitanus-tunetanus-scorpion-toxin-produces-potent-analgesia-in-rodents
#1
Riadh Maatoug, Jed Jebali, Régis Guieu, Michel De Waard, Riadh Kharrat
This work reports the purification of new potent scorpion neuropeptide, named BotAF, by an activity-guided screening approach. BotAF is a 64-residue long-chain peptide that shares very high similarity with the original β-like scorpion toxin group, in which several peptides have been characterized to be anti-nociceptive in rodents. BotAF administration to rodents does not produce any toxicity or motor impairment, including at high doses. In all models investigated, BotAF turned out to be an efficient peptide in abolishing acute and inflammatory (both somatic and visceral) pain in rodents...
January 11, 2018: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/29320748/true-molecular-scale-visualization-of-variable-clustering-properties-of-ryanodine-receptors
#2
Isuru Jayasinghe, Alexander H Clowsley, Ruisheng Lin, Tobias Lutz, Carl Harrison, Ellen Green, David Baddeley, Lorenzo Di Michele, Christian Soeller
Signaling nanodomains rely on spatial organization of proteins to allow controlled intracellular signaling. Examples include calcium release sites of cardiomyocytes where ryanodine receptors (RyRs) are clustered with their molecular partners. Localization microscopy has been crucial to visualizing these nanodomains but has been limited by brightness of markers, restricting the resolution and quantification of individual proteins clustered within. Harnessing the remarkable localization precision of DNA-PAINT (<10 nm), we visualized punctate labeling within these nanodomains, confirmed as single RyRs...
January 9, 2018: Cell Reports
https://www.readbyqxmd.com/read/29284662/junctional-trafficking-and-restoration-of-retrograde-signaling-by-the-cytoplasmic-ryr1-domain
#3
Alexander Polster, Stefano Perni, Dilyana Filipova, Ong Moua, Joshua D Ohrtman, Hicham Bichraoui, Kurt G Beam, Symeon Papadopoulos
The type 1 ryanodine receptor (RyR1) in skeletal muscle is a homotetrameric protein that releases Ca2+ from the sarcoplasmic reticulum (SR) in response to an "orthograde" signal from the dihydropyridine receptor (DHPR) in the plasma membrane (PM). Additionally, a "retrograde" signal from RyR1 increases the amplitude of the Ca2+ current produced by CaV1.1, the principle subunit of the DHPR. This bidirectional signaling is thought to depend on physical links, of unknown identity, between the DHPR and RyR1. Here, we investigate whether the isolated cytoplasmic domain of RyR1 can interact structurally or functionally with CaV1...
December 28, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/29251109/human-olfactory-ensheathing-cell-transplantation-improves-motor-function-in-a-mouse-model-of-type-3-spinocerebellar-ataxia
#4
Jeanne Hsieh, Jen-Wei Liu, Horng-Jyh Harn, Kuo-Wei Hsueh, Karthyayani Rajamani, Yu-Chen Deng, Chih-Min Chia, Woei-Cheang Shyu, Shinn-Zong Lin, Tzyy-Wen Chiou
Spinocerebellar ataxia (SCA) is a progressive neurodegenerative disease that affects the cerebellum and spinal cord. Among the 40 types of SCA, SCA type 3 (SCA3), also referred to as Machado-Joseph disease, is the most common. In the present study, we investigated the therapeutic effects of intracranial transplantation of human olfactory ensheathing cells (hOECs) in the ATXN3-84Q mouse model of SCA3. Motor function begins to decline in ATXN3-84Q transgenic mice at approximately 13 weeks of age. ATXN3-84Q mice that received intracranial hOEC transplantation into the dorsal raphe nucleus of the brain exhibited significant improvements in motor function, as measured by the rotarod performance test and footprint pattern analysis...
October 2017: Cell Transplantation
https://www.readbyqxmd.com/read/29241198/fam3a-protects-against-glutamate-induced-toxicity-by-preserving-calcium-homeostasis-in-differentiated-pc12-cells
#5
Qing Song, Wen-Li Gou, Yu-Liang Zou
BACKGROUND/AIMS: Stroke is the leading cause of adult disability, and glutamate-induced dysregulation of intracellular Ca2+ homeostasis is a key mechanism. FAM3A is the first member of the family with sequence similarity 3 (FAM3) gene family, and its biological function remains largely unknown. We have recently reported that FAM3A exerts protective effects against oxidative stress and mitochondrial dysfunction in HT22 cells. METHODS: Here, we investigated the protective effects of FAM3A using a glutamate-induced neuronal injury model in nerve growth factor (NGF)-differentiated PC12 cells...
December 12, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29237755/differential-contribution-of-ca2-sources-to-day-and-night-bk-current-activation-in-the-circadian-clock
#6
Joshua P Whitt, Beth A McNally, Andrea L Meredith
Large conductance K+ (BK) channels are expressed widely in neurons, where their activation is regulated by membrane depolarization and intracellular Ca2+ (Ca2+i). To enable this regulation, BK channels functionally couple to both voltage-gated Ca2+ channels (VGCCs) and channels mediating Ca2+ release from intracellular stores. However, the relationship between BK channels and their specific Ca2+ source for particular patterns of excitability is not well understood. In neurons within the suprachiasmatic nucleus (SCN)-the brain's circadian clock-BK current, VGCC current, and Ca2+i are diurnally regulated, but paradoxically, BK current is greatest at night when VGCC current and Ca2+i are reduced...
December 13, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/29235708/chlorantraniliprole-resistance-and-its-biochemical-and-new-molecular-target-mechanisms-in-laboratory-and-field-strains-of-chilo-suppressalis-walker
#7
Sun Yang, Lu Xu, Chen Qiong, Wenjing Qin, Huang Shuijin, Houguo Qin
BACKGROUND: The rice striped stem borer (SSB), Chilo suppressalis (Walker), is one of the most economically important and destructive rice pests in China. To date, the efficiency of conventional insecticides has decreased greatly because of the development of high resistance. Since the introduction of chlorantraniliprole in 2008, SSB has presented resistance issues. RESULTS: In this study, lab resistant strains R1 and R2 (RR of 38.8 and 110.4, respectively) were established and a field population HR (RR of 249...
December 13, 2017: Pest Management Science
https://www.readbyqxmd.com/read/29214114/calcium-dysregulation-in-alzheimer-s-disease-a-target-for-new-drug-development
#8
Yong Wang, Yun Shi, Huafeng Wei
Alzheimer's disease (AD) is a devastating neurodegenerative disorder and the most common cause of dementia among aged people whose population is rapidly increasing. AD not only seriously affects the patient's physical health and quality of life, but also adds a heavy burden to the patient's family and society. It is urgent to understand AD pathogenesis and develop the means of prevention and treatment. AD is a chronic devastating neurodegenerative disease without effective treatment. Current approaches for management focus on helping patients relieve or delay the symptoms of cognitive dysfunction...
August 2017: Journal of Alzheimer's Disease and Parkinsonism
https://www.readbyqxmd.com/read/29201571/transcriptomic-profiling-of-mtor-and-ryanodine-receptor-signaling-molecules-in-developing-zebrafish-in-the-absence-and-presence-of-pcb-95
#9
Daniel F Frank, Galen W Miller, Richard E Connon, Juergen Geist, Pamela J Lein
The mechanistic target of rapamycin (mTOR) and ryanodine receptor (RyR) signaling pathways regulate fundamental processes of neurodevelopment, and genetic mutations within these pathways have been linked to neurodevelopmental disorders. While previous studies have established that these signaling molecules are expressed in developing zebrafish, a detailed characterization of the ontogenetic profile of these signaling molecules is lacking. Thus, we evaluated the spatiotemporal expression of key transcripts in mTOR and RyR signaling pathways in wildtype zebrafish at 24, 72 and 120 hours post fertilization (hpf)...
2017: PeerJ
https://www.readbyqxmd.com/read/29191465/crystal-structure-of-ryanodine-receptor-n-terminal-domain-from-plutella-xylostella-reveals-two-potential-species-specific-insecticide-targeting-sites
#10
Lianyun Lin, Chen Liu, Juan Qin, Jie Wang, Shengjie Dong, Wei Chen, Weiyi He, Qingzhi Gao, Minsheng You, Zhiguang Yuchi
Ryanodine receptors (RyRs) are large calcium-release channels located in sarcoplasmic reticulum membrane. They play a central role in excitation-contraction coupling of muscle cells. Three commercialized insecticides targeting pest RyRs generate worldwide sales over 2 billion U.S. dollars annually, but the structure of insect RyRs remains elusive, hindering our understanding of the mode of action of RyR-targeting insecticides and the development of insecticide resistance in pests. Here we present the crystal structure of RyR N-terminal domain (NTD) (residue 1-205) at 2...
December 2, 2017: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29170096/npb-2-modulates-ryanodine-receptors-from-the-endoplasmic-reticulum-in-rat-brain
#11
Qiyue Jia, Guihua Du, Yu Li, Zhiping Wang, Jie Xie, Junwang Gu, Guangming Yin, Shuyun Zhang, Yanyan Gao, Fankun Zhou, Chang Feng, Guangqin Fan
Although the neurotoxic mechanism of lead (Pb(2+)) has been extensively studied, it is not well understood. The effects of Pb(2+) on free cytosolic calcium (Ca(2+)) concentration and calcium-regulated events have been suggested to be major mechanisms in Pb(2+) toxicity. Based on our previous findings that Pb(2+) changes calcium release through ryanodine receptors (RyRs), the modulation of endoplasmic reticulum (ER) vesicular RyRs by Pb(2+) was investigated further in the present study. The results of [(3)H]ryanodine binding assays showed that in the presence of a free Ca(2+) concentration ([Ca(2+)]f) of 100μM, Pb(2+) modulated the equilibrium of [(3)H]ryanodine binding to brain RyRs, with a U-type dose-response curve, where minimal binding was observed at a free Pb(2+) concentration ([Pb(2+)]f) of 0...
November 20, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29162778/ryanodine-receptor-type-2-plays-a-role-in-the-development-of-cardiac-fibrosis-under-mechanical-stretch-through-tgf%C3%AE-1
#12
Zhiwen Ding, Jie Yuan, Yanyan Liang, Jian Wu, Hui Gong, Yong Ye, Guoliang Jiang, Peipei Yin, Yang Li, Guoping Zhang, Chunjie Yang, Junjie Guo, Zhidan Chen, Xingxu Wang, Liqing Weng, Yunzeng Zou
Ryanodine receptor type 2 (RyR-2), the main Ca2+ release channel from sarcoplasmic reticulum in cardiomyocytes, plays a vital role in the regulation ofmyocardial contractile function and cardiac hypertrophy. However, the role of RyR-2 in cardiac fibrosis during the development of cardiac hypertrophy remains unclear.In this study, we examined whether RyR-2 regulates TGFβ1, which is secreted from cardiomyocytes and exerts on cardiac fibrosis using cultured cardiomyocytes and cardiac fibroblasts of neonatal rats...
December 12, 2017: International Heart Journal
https://www.readbyqxmd.com/read/29154060/efficacy-and-safety-of-a-combination-of-red-yeast-rice-and-olive-extract-in-hypercholesterolemic-patients-with-and-without-statin-associated-myalgia
#13
Christian Tshongo Muhindo, Sylvie A Ahn, Michel F Rousseau, Yvan Dierckxsens, Michel P Hermans
Cholesfytol®, a lipid-lowering dietary supplement with antioxidant and anti-atherosclerotic properties, combines red yeast rice (RYR) and olive extract (5mg hydroxytyrosol equivalent) and represents an alternative for patients who do not wish or are unable to use chemical statins, including individuals with previous statin-associated muscle symptoms (SAMS). A 2-months observational non-randomized study was performed to evaluate the efficacy, tolerance and safety of Cholesfytol® (1 tablet/day) in 642 hypercholesterolemic patients (mean age: 59 yrs; total cholesterol (TC) ≥200; LDL-C ≥140mg/dl)...
December 2017: Complementary Therapies in Medicine
https://www.readbyqxmd.com/read/29151485/evolution-of-vertebrate-ryanodine-receptors-family-in-relation-to-functional-divergence-and-conservation
#14
Zhiwen Ding, Juan Peng, Yanyan Liang, Chunjie Yang, Guoliang Jiang, Jun Ren, Yunzeng Zou
Ryanodine receptors (RyRs), the large homotetrameric protein complexes, regulate the release of calcium from intracellular stores into the cytosol and play vital roles in the excitation-contraction coupling of cells. However, the evolutionary relationship of RyRs in vertebrates has yet to be elucidated. We identified 22 RyRs from Homo sapiens, Mus musculus, Rattus norvegicus, Gallus gallus, Anolis carolinensis, Rana catesbeiana, and Danio rerio. The phylogenetic relationship, motifs analysis and reconstruction of ancestral RyRs showed that the members of RyR family in vertebrates were grouped into three clades: the RyR1 clade, the RyR2 clade, and the RyR3 clade...
November 17, 2017: International Heart Journal
https://www.readbyqxmd.com/read/29150444/toll-like-receptor-4-induced-ryanodine-receptor-2-oxidation-and-sarcoplasmic-reticulum-ca2-leakage-promote-cardiac-contractile-dysfunction-in-sepsis
#15
Jie Yang, Rui Zhang, Xin Jiang, Jingzhang Lv, Ying Li, Hongyu Ye, Wenjuan Liu, Gang Wang, Cuicui Zhang, Na Zheng, Ming Dong, Yan Wang, Peiya Chen, Kumar Santosh, Yong Jiang, Jie Liu
Studies suggest the potential role of sarcoplasmic reticulum (SR) Ca2+ leak in cardiac contractile dysfunction in sepsis. However, direct supporting evidence is lacking, and the mechanisms underlying this SR leak are poorly understood. Here, we investigated the changes in cardiac Ca2+ handling and contraction in LPS-treated rat cardiomyocytes and a mouse model of polymicrobial sepsis produced by cecal ligation and puncture (CLP). LPS decreased the systolic Ca2+ transient and myocyte contraction, as well as SR Ca2+ content...
November 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29145393/estimating-the-probabilities-of-rare-arrhythmic-events-in-multiscale-computational-models-of-cardiac-cells-and-tissue
#16
Mark A Walker, Viatcheslav Gurev, John J Rice, Joseph L Greenstein, Raimond L Winslow
Ectopic heartbeats can trigger reentrant arrhythmias, leading to ventricular fibrillation and sudden cardiac death. Such events have been attributed to perturbed Ca2+ handling in cardiac myocytes leading to spontaneous Ca2+ release and delayed afterdepolarizations (DADs). However, the ways in which perturbation of specific molecular mechanisms alters the probability of ectopic beats is not understood. We present a multiscale model of cardiac tissue incorporating a biophysically detailed three-dimensional model of the ventricular myocyte...
November 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/29131945/enantioselectivity-of-2-2-3-5-6-pentachlorobiphenyl-pcb-95-atropisomers-toward-ryanodine-receptors-ryrs-and-their-influences-on-hippocampal-neuronal-networks
#17
Wei Feng, Jing Zheng, Gaelle Robin, Yao Dong, Makoto Ichikawa, Yoshihisa Inoue, Tadashi Mori, Takeshi Nakano, Isaac N Pessah
Nineteen ortho-substituted PCBs are chiral and found enantioselectively enriched in ecosystems. Their differential actions on biological targets are not understood. PCB 95 (2,2',3,5',6-pentachlorobiphenyl), a chiral PCB of current environmental relevance, is among the most potent towards modifying ryanodine receptors (RyR) function and Ca2+ signaling. PCB 95 atropisomers are separated and assigned aR- and aS-PCB 95 using 3 chiral-columns HPLC and circular dichroism spectroscopy. Studies of RyR1-enriched microsomes show aR-PCB 95 with >4X greater potency (EC50=0...
November 13, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/29122978/the-structural-basis-of-ryanodine-receptor-ion-channel-function
#18
REVIEW
Gerhard Meissner
Large-conductance Ca2+ release channels known as ryanodine receptors (RyRs) mediate the release of Ca2+ from an intracellular membrane compartment, the endo/sarcoplasmic reticulum. There are three mammalian RyR isoforms: RyR1 is present in skeletal muscle; RyR2 is in heart muscle; and RyR3 is expressed at low levels in many tissues including brain, smooth muscle, and slow-twitch skeletal muscle. RyRs form large protein complexes comprising four 560-kD RyR subunits, four ∼12-kD FK506-binding proteins, and various accessory proteins including calmodulin, protein kinases, and protein phosphatases...
December 4, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/29107248/molecular-cloning-mrna-expression-and-alternative-splicing-of-a-ryanodine-receptor-gene-from-the-citrus-whitefly-dialeurodes-citri-ashmead
#19
Guo-Rui Yuan, Ke-Yi Wang, Xing Mou, Ruo-Yu Luo, Wei Dou, Jin-Jun Wang
Insect ryanodine receptors are the main targets of diamide insecticides that have highly selective insecticidal activity but are less toxic to mammals. Therefore, these insecticides are ideal for pest control. Ryanodine receptors (RyRs) play a critical role in Ca(2+) signaling in muscle and non-muscle cells. In this study, we cloned the complete cDNA (DcRyR) of the RyR from the citrus whitefly, Dialeurodes citri, a serious pest of citrus orchards in China. The open reading frame of RyR is 15,378bp long and encodes a protein with 5126 amino acids with a computed molecular weight of 579...
October 2017: Pesticide Biochemistry and Physiology
https://www.readbyqxmd.com/read/29107242/silence-of-inositol-1-4-5-trisphosphate-receptor-expression-decreases-cyantraniliprole-susceptibility-in-bemisia-tabaci
#20
Lei Guo, Pei Liang, Kuan Fang, Dong Chu
Cyantraniliprole is the second active ingredient of anthranilic diamide insecticide, and the first to control a cross-spectrum of chewing and sucking pests such as sweetpotato whitefly, Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae). The inositol 1,4,5-trisphosphate receptor (IP3R) and ryanodine receptor (RyR) are two families of Ca(2+) release channels to raise the cytoplasmic free calcium concentration when it is activated by various extracellular stimuli. Previous study proved the over-expression of ryanodine receptor (RyR) was associated with the resistance to diamide insecticides, while the roles of IP3R in diamide resistance remain unknown...
October 2017: Pesticide Biochemistry and Physiology
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