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https://www.readbyqxmd.com/read/27932490/c-terminus-of-the-p4-atpase-atp8a2-functions-in-protein-folding-and-regulation-of-phospholipid-flippase-activity
#1
Madhavan Chalat, Kody Moleschi, Robert S Molday
ATP8A2 is a P4-ATPase that flips phosphatidylserine and phosphatidylethanolamine across cell membranes. This generates membrane phospholipid asymmetry, a property important in many cellular processes including vesicle trafficking. ATP8A2 deficiency causes severe neurodegenerative diseases. We have investigated the role of the C-terminus of ATP8A2 in its expression, subcellular localization, interaction with its subunit CDC50A, and function as a phosphatidylserine flippase. C-terminal deletion mutants exhibited a reduced tendency to solubilize in mild detergent and exit the endoplasmic reticulum...
December 8, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27923791/reduced-density-and-altered-regulation-of-rat-atrial-l-type-ca2-current-in-rat-heart-failure
#2
Richard C Bond, Simon M Bryant, Judy J Watson, Jules C Hancox, Clive H Orchard, Andrew F James
Atrial L-type Ca(2+) current (ICaL) downregulation in heart failure contributes to the pathogenesis of atrial fibrillation and is proposed to involve reduction in channel phosphorylation by PKA. The regulation of atrial ICaL was examined in heart failure. Anesthetized adult male Wistar rats underwent surgical coronary artery ligation (CAL, N=10) or equivalent sham-operation (Sham, N=12). Left atrial myocytes were isolated ~18 weeks post-surgery and whole-cell currents recorded (holding potential=-80 mV). ICaL activated by depolarizing pulses to voltages from -40 to +50 mV were normalized to cell capacitance and current density-voltage relations plotted...
December 6, 2016: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/27917110/adolescent-mice-are-resilient-to-alcohol-withdrawal-induced-anxiety-and-changes-in-indices-of-glutamate-function-within-the-nucleus-accumbens
#3
Kaziya M Lee, Michal A Coelho, Hadley A McGregor, Noah R Solton, Matan Cohen, Karen K Szumlinski
Binge-drinking is the most prevalent form of alcohol abuse and while an early life history of binge-drinking is a significant risk factor for subsequent alcoholism and co-morbid affective disorders, relatively little is known regarding the biobehavioral impact of binge-drinking during the sensitive neurodevelopmental period of adolescence. In adult mice, a month-long history of binge-drinking elicits a hyper-glutamatergic state within the nucleus accumbens (Acb), coinciding with hyper-anxiety. Herein, we employed a murine model of binge-drinking to determine whether or not: (1) withdrawal-induced changes in brain and behavior differ between adult and adolescent bingers; and (2) increased behavioral signs of negative affect and changes in Acb expression of glutamate-related proteins would be apparent in adult mice with less chronic binge-drinking experience (14 days, approximating the duration of mouse adolescence)...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27917108/structural-and-functional-consequences-of-connexin-36-cx36-interaction-with-calmodulin
#4
Ryan C F Siu, Ekaterina Smirnova, Cherie A Brown, Christiane Zoidl, David C Spray, Logan W Donaldson, Georg Zoidl
Functional plasticity of neuronal gap junctions involves the interaction of the neuronal connexin36 with calcium/calmodulin-dependent kinase II (CaMKII). The important relationship between Cx36 and CaMKII must also be considered in the context of another protein partner, Ca(2+) loaded calmodulin, binding an overlapping site in the carboxy-terminus of Cx36. We demonstrate that CaM and CaMKII binding to Cx36 is calcium-dependent, with Cx36 able to engage with CaM outside of the gap junction plaque. Furthermore, Ca(2+) loaded calmodulin activates Cx36 channels, which is different to other connexins...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27906494/alcohol-dependent-molecular-adaptations-of-the-nmda-receptor-system
#5
REVIEW
Nadege Morisot, Dorit Ron
Phenotypes such as motivation to consume alcohol, goal-directed alcohol seeking and habit formation contribute to the mechanisms underlying heavy alcohol use. Learning and memory processes greatly contribute to the establishment and maintenance of these behavioral phenotypes. The N-Methyl-D-Aspartate receptor (NMDAR) is a driving force of synaptic plasticity, a key cellular hallmark of learning and memory. Here, we describe data in rodents and humans linking signaling molecules that center around the NMDARs and behaviors associated with the development and/or maintenance of alcohol abuse...
December 1, 2016: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/27906053/attenuated-ca-2-release-in-a-mouse-model-of-limb-girdle-muscular-dystrophy-2a
#6
Marino DiFranco, Irina Kramerova, Julio L Vergara, Melissa Jan Spencer
BACKGROUND: Mutations in CAPN3 cause limb girdle muscular dystrophy type 2A (LGMD2A), a progressive muscle wasting disease. CAPN3 is a non-lysosomal, Ca-dependent, muscle-specific proteinase. Ablation of CAPN3 (calpain-3 knockout (C3KO) mice) leads to reduced ryanodine receptor (RyR1) expression and abnormal Ca2+/calmodulin-dependent protein kinase II (Ca-CaMKII)-mediated signaling. We previously reported that Ca(2+) release measured by fura2-FF imaging in response to single action potential stimulation was reduced in old C3KO mice; however, the use of field stimulation prevented investigation of the mechanisms underlying this impairment...
February 24, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27891586/celastrol-attenuates-cadmium-induced-neuronal-apoptosis-via-inhibiting-ca-2-camkii-dependent-akt-mtor-pathway
#7
Ruijie Zhang, Yu Zhu, Xiaoqing Dong, Beibei Liu, Nana Zhang, Xiaoxue Wang, Lei Liu, Chong Xu, Shile Huang, Long Chen
Cadmium (Cd), an environmental and industrial pollutant, affects the nervous system and consequential neurodegenerative disorders. Recently we have shown that celastrol prevents Cd-induced neuronal cell death partially by suppressing Akt/mTOR pathway. However, the underlying mechanism remains to be elucidated. Here we show that celastrol attenuated Cd-elevated intracellular free calcium ([Ca(2+) ]i ) level and apoptosis in neuronal cells. Celastrol prevented Cd-induced neuronal apoptosis by inhibiting Akt-mediated mTOR pathway, as inhibition of Akt with Akt inhibitor X or ectopic expression of dominant negative Akt reinforced celastrol's prevention of Cd-induced phosphorylation of S6K1/4E-BP1 and cell apoptosis...
November 27, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27889915/constitutive-regulation-of-the-glutamate-aspartate-transporter-eaat1-by-calcium-calmodulin-dependent-protein-kinase-ii
#8
Aarti R Chawla, Derrick E Johnson, Agnes S Zybura, Benjamin P Leeds, Ross M Nelson, Andy Hudmon
Glutamate clearance by astrocytes is an essential part of normal excitatory neurotransmission. Failure to adapt or maintain low levels of glutamate in the central nervous system is associated with multiple acute and chronic neurodegenerative diseases. The primary excitatory amino acid transporters in human astrocytes are EAAT1 and EAAT2 (GLAST and GLT-1 respectively in rodents). While the inhibition of calcium/calmodulin-dependent kinase (CaMKII), a ubiquitously-expressed serine/threonine protein kinase, results in diminished glutamate uptake in cultured primary rodent astrocytes (Ashpole et al...
November 27, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27884929/pro-nociceptive-migraine-mediator-cgrp-provides-neuroprotection-of-sensory-cortical-and-cerebellar-neurons-via-multi-kinase-signaling
#9
Polina A Abushik, Geneviève Bart, Paula Korhonen, Hanna Leinonen, Raisa Giniatullina, Dmitry A Sibarov, Anna-Liisa Levonen, Tarja Malm, Sergei M Antonov, Rashid Giniatullin
BACKGROUND: Blocking the pro-nociceptive action of CGRP is one of the most promising approaches for migraine prophylaxis. The aim of this study was to explore a role for CGRP as a neuroprotective agent for central and peripheral neurons. METHODS: The viability of isolated rat trigeminal, cortical and cerebellar neurons was tested by fluorescence vital assay. Engagement of Nrf2 target genes was analyzed by qPCR. The neuroprotective efficacy of CGRP in vivo was tested in mice using a permanent cerebral ischemia model...
November 24, 2016: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/27882934/macrophage-dependent-il-1%C3%AE-production-induces-cardiac-arrhythmias-in-diabetic-mice
#10
Gustavo Monnerat, Micaela L Alarcón, Luiz R Vasconcellos, Camila Hochman-Mendez, Guilherme Brasil, Rosana A Bassani, Oscar Casis, Daniela Malan, Leonardo H Travassos, Marisa Sepúlveda, Juan Ignacio Burgos, Martin Vila-Petroff, Fabiano F Dutra, Marcelo T Bozza, Claudia N Paiva, Adriana Bastos Carvalho, Adriana Bonomo, Bernd K Fleischmann, Antonio Carlos Campos de Carvalho, Emiliano Medei
Diabetes mellitus (DM) encompasses a multitude of secondary disorders, including heart disease. One of the most frequent and potentially life threatening disorders of DM-induced heart disease is ventricular tachycardia (VT). Here we show that toll-like receptor 2 (TLR2) and NLRP3 inflammasome activation in cardiac macrophages mediate the production of IL-1β in DM mice. IL-1β causes prolongation of the action potential duration, induces a decrease in potassium current and an increase in calcium sparks in cardiomyocytes, which are changes that underlie arrhythmia propensity...
November 24, 2016: Nature Communications
https://www.readbyqxmd.com/read/27875595/phosphorylation-of-serine-235-of-the-hepatitis-c-virus-non-structural-protein-ns5a-by-multiple-kinases
#11
Kuan-Ying Lee, Yi-Hung Chen, Shih-Chin Hsu, Ming-Jiun Yu
Phosphorylation at serine 235 (S235) of the hepatitis C virus (HCV) non-structural protein 5A (NS5A) plays a critical role in the viral life cycle. For medical and virological interests, we exploited the HEK293T kidney cells to test 3 candidate protein kinases on NS5A S235 phosphorylation. Inhibitors that inhibit casein kinase I α (CKIα), polo-like kinase I (PlKI) or calmodulin-dependent kinase II (CaMKII) all reduced NS5A S235 phosphorylation. CKIα was studied previously and PlKI had severe cytotoxicity, thus CaMKII was selected for validation in the Huh7...
2016: PloS One
https://www.readbyqxmd.com/read/27874976/etidronate-rescues-cognitive-deficits-through-improving-synaptic-transmission-and-suppressing-apoptosis-in-2-vessel-occlusion-model-rats
#12
Wen Li, Huijuan Yuan, Yao Yu, Yuen-Ki Cheong, Guogang Ren, Zhuo Yang
Vascular dementia (VD) is a neurodegenerative disorder caused by the reduction of cerebral blood flow. It shows a progressive cognitive impairment. In our previous study, we found that etidronate (ET) showed neuroprotective effects against glutamate-injured PC12 cells. Thus in this study, we aimed to observe the effects of ET on learning and memory impairment and the related mechanism in 2-vessel occlusion (2VO) model rats. Rats were administered a permanent bilateral common carotid artery occlusion to induce VD model...
November 22, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27871090/the-genomic-basis-of-circadian-and-circalunar-timing-adaptations-in-a-midge
#13
Tobias S Kaiser, Birgit Poehn, David Szkiba, Marco Preussner, Fritz J Sedlazeck, Alexander Zrim, Tobias Neumann, Lam-Tung Nguyen, Andrea J Betancourt, Thomas Hummel, Heiko Vogel, Silke Dorner, Florian Heyd, Arndt von Haeseler, Kristin Tessmar-Raible
Organisms use endogenous clocks to anticipate regular environmental cycles, such as days and tides. Natural variants resulting in differently timed behaviour or physiology, known as chronotypes in humans, have not been well characterized at the molecular level. We sequenced the genome of Clunio marinus, a marine midge whose reproduction is timed by circadian and circalunar clocks. Midges from different locations show strain-specific genetic timing adaptations. We examined genetic variation in five C. marinus strains from different locations and mapped quantitative trait loci for circalunar and circadian chronotypes...
December 1, 2016: Nature
https://www.readbyqxmd.com/read/27855397/inhibition-of-cartilage-acidic-protein-1-reduces-ultraviolet-b-irradiation-induced-apoptosis-through-p38-mitogen-activated-protein-kinase-and-jun-amino-terminal-kinase-pathways
#14
Yinghong Ji, Xianfang Rong, Dan Li, Lei Cai, Jun Rao, Yi Lu
BACKGROUND/AIMS: Ultraviolet B (UVB) irradiation can easily induce apoptosis in human lens epithelial cells (HLECs) and further lead to various eye diseases including cataract. Here for the first time, we investigated the role of cartilage acidic protein 1 (CRTAC1) gene in UVB irradiation induced-apoptosis in HLECs. METHODS: Three groups of HLECs were employed including model group, empty vector group, and CRTAC1 interference group. RESULTS: After UVB irradiation, the percentage of primary apoptotic cells was obviously fewer in CRTAC1 interference group...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27837188/capsular-stroke-modeling-based-on-somatotopic-mapping-of-motor-fibers
#15
Hanlim Song, Wonbin Jung, Eulgi Lee, Ji-Young Park, Min Sun Kim, Min-Cheol Lee, Hyoung-Ihl Kim
Recently, several capsular stroke models have been reported with different targets of destruction. This study was performed to establish an accurate internal capsule (IC) target for capsular stroke modeling in rats. We injected adeno-associated virus serotype 5 (AAV)-CaMKII-EYFP into forelimb motor cortex and AAV-CaMKII-mCherry into hindlimb motor cortex (n = 9) to anterogradely trace the pyramidal fibers and map their somatotopic distribution in the IC. On the basis of the neural tracing results, we created photothrombotic infarct lesions in rat forelimb and hindlimb motor fiber (FMF and HMF) areas of the IC (n = 29) and assessed motor behavior using a forelimb-use asymmetry test, a foot-fault test, and a single-pellet reaching test...
November 11, 2016: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/27816787/gastrodin-relieved-complete-freund-s-adjuvant-induced-spontaneous-pain-by-inhibiting-inflammatory-response
#16
Ting Sun, Jian Wang, Xiang Li, Yu-Jiao Li, Dan Feng, Wen-Long Shi, Ming-Gao Zhao, Jian-Bo Wang, Yu-Mei Wu
The analgesic effects of gastrodin (GAS), an active component derived from the Chinese herb Tian ma (Gastrodia elata Blume), on chronic inflammatory pain of mice and the involved molecular mechanisms were investigated. GAS significantly attenuated mice chronic inflammatory pain induced by hindpaw injection of complete Freund's adjuvant (CFA) and the accompanying anxiety-like behaviors. GAS administration reduced CFA-induced up-regulation of GluR1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, GluN2A- and GluN2B-containing N-methyl-d-aspartate (NMDA) receptors, and Ca(2+)/calmodulin-dependent protein kinase II-alpha (CaMKII-α) in the anterior cingulate cortex (ACC)...
November 3, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27816760/high-molecular-weight-cocoa-procyanidins-possess-enhanced-insulin-enhancing-and-insulin-mimetic-activities-in-human-primary-skeletal-muscle-cells-compared-to-smaller-procyanidins
#17
Suzanne M Bowser, William T Moore, Ryan P McMillan, Melanie R Dorenkott, Katheryn M Goodrich, Liyun Ye, Sean F O'Keefe, Matthew W Hulver, Andrew P Neilson
Dysregulation of glucose metabolism is a primary hallmark of metabolic disease (i.e., diabetes, obesity, etc.). Complementary nonpharmaceutical strategies are needed to prevent and/or ameliorate dysregulation of glucose metabolism and prevent progression from normoglycemia to prediabetes and type 2 diabetes across the lifespan. Cocoa compounds, particularly the procyanidins, have shown promise for improving insulin sensitivity and blood glucose homeostasis. However, the molecular mechanisms by which cocoa procyanidins exert these functions remain poorly understood...
January 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/27815504/the-arrhythmogenic-calmodulin-mutation-d129g-dysregulates-cell-growth-calmodulin-dependent-kinase-ii-activity-and-cardiac-function-in-zebrafish
#18
Martin W Berchtold, Triantafyllos Zacharias, Katarzyna Kulej, Kevin Wang, Raffaela Torggler, Thomas Jespersen, Jau-Nian Chen, Martin R Larsen, Jonas M La Cour
Calmodulin (CaM) is a Ca2+ binding protein modulating multiple targets of which several are associated with cardiac pathophysiology. Recently, CaM mutations were linked to heart arrhythmia. CaM is crucial for cell growth and viability, yet the effect of the arrhythmogenic CaM mutations on cell viability as well as heart rhythm remains unknown and only a few targets with relevance for heart physiology have been analyzed for their response to mutant CaM. We show that the arrhythmia-associated CaM mutants support growth and viability of DT40 cells in the absence of wt CaM except for the LQTS mutant CaM D129G...
November 4, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27808115/multi-phasic-bi-directional-chemotactic-responses-of-the-growth-cone
#19
Honda Naoki, Makoto Nishiyama, Kazunobu Togashi, Yasunobu Igarashi, Kyonsoo Hong, Shin Ishii
The nerve growth cone is bi-directionally attracted and repelled by the same cue molecules depending on the situations, while other non-neural chemotactic cells usually show uni-directional attraction or repulsion toward their specific cue molecules. However, how the growth cone differs from other non-neural cells remains unclear. Toward this question, we developed a theory for describing chemotactic response based on a mathematical model of intracellular signaling of activator and inhibitor. Our theory was first able to clarify the conditions of attraction and repulsion, which are determined by balance between activator and inhibitor, and the conditions of uni- and bi-directional responses, which are determined by dose-response profiles of activator and inhibitor to the guidance cue...
November 3, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27806984/dietary-%C3%AE-linolenic-acid-supplementation-alters-skeletal-muscle-plasma-membrane-lipid-composition-sarcolemmal-fat-cd36-abundance-and-palmitate-transport-rates
#20
Zane Chorner, Pierre-Andre Barbeau, Laura Castellani, David C Wright, Adrian Chabowski, Graham P Holloway
The cellular processes influenced by consuming polyunsaturated fatty acids remains poorly defined. Within skeletal muscle, a rate-limiting step in fatty acid oxidation is the of movement lipids across the sarcolemmal membrane, and therefore we aimed to determine the effects of consuming Flaxseed oil high in α-linolenic acid (ALA), on plasma membrane lipid composition and the capacity to transport palmitate. Rats fed a diet supplemented with ALA (10%) displayed marked increases in n-3 PUFAs within whole muscle and sarcolemmal membranes (~5-fold), at the apparent expense of arachidonic acid (-50%)...
November 2, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
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