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https://www.readbyqxmd.com/read/28531964/non-electron-transfer-chain-mitochondrial-defects-differently-regulate-hif-1%C3%AE-degradation-and-transcription
#1
Antonina N Shvetsova, Daniela Mennerich, Juha M Kerätär, J Kalervo Hiltunen, Thomas Kietzmann
Mitochondria are the main consumers of molecular O2 in a cell as well as an abundant source of reactive oxygen species (ROS). Both, molecular oxygen and ROS are powerful regulators of the hypoxia-inducible factor-1α-subunit (HIF-α). While a number of mechanisms in the oxygen-dependent HIF-α regulation are quite well known, the view with respect to mitochondria is less clear. Several approaches using pharmacological or genetic tools targeting the mitochondrial electron transport chain (ETC) indicated that ROS, mainly formed at the Rieske cluster of complex III of the ETC, are drivers of HIF-1α activation...
May 8, 2017: Redox Biology
https://www.readbyqxmd.com/read/28531217/store-operated-ca2-entry-supports-contractile-function-in-hearts-of-hibernators
#2
Olga V Nakipova, Alexey S Averin, Edward V Evdokimovskii, Oleg Yu Pimenov, Leonid Kosarski, Dmitriy Ignat'ev, Andrey Anufriev, Yuri M Kokoz, Santiago Reyes, Andre Terzic, Alexey E Alekseev
Hibernators have a distinctive ability to adapt to seasonal changes of body temperature in a range between 37°C and near freezing, exhibiting, among other features, a unique reversibility of cardiac contractility. The adaptation of myocardial contractility in hibernation state relies on alterations of excitation contraction coupling, which becomes less-dependent from extracellular Ca2+ entry and is predominantly controlled by Ca2+ release from sarcoplasmic reticulum, replenished by the Ca2+-ATPase (SERCA)...
2017: PloS One
https://www.readbyqxmd.com/read/28530826/high-speed-atomic-force-microscopy-reveals-loss-of-nuclear-pore-resilience-as-a-dying-code-in-colorectal-cancer-cells
#3
Mahmoud Shaaban Mohamed, Akiko Kobayashi, Azuma Taoka, Takahiro Watanabe-Nakayama, Yosuke Kikuchi, Masaharu Hazawa, Toshinari Minamoto, Yoshihiro Fukumori, Noriyuki Kodera, Takayuki Uchihashi, Toshio Ando, Richard W Wong
Nuclear pore complexes (NPCs) are the sole turnstile implanted in the nuclear envelope (NE), acting as a central nano-regulator of transport between the cytosol and the nucleus. NPCs consist of ~30 proteins, termed nucleoporins. About one-third of nucleoporins harbour natively unstructured, intrinsically disordered phenylalanine-glycine strings (FG-Nups), which engage in transport selectivity. Because the barriers insert deeply in the NPC, they are nearly inaccessible. Several in vitro barrier models have been proposed; however, the dynamic FG-Nups protein molecules themselves are imperceptible in vivo...
May 22, 2017: ACS Nano
https://www.readbyqxmd.com/read/28530703/trpv4-plays-a-role-in-breast-cancer-cell-migration-via-ca-2-dependent-activation-of-akt-and-downregulation-of-e-cadherin-cell-cortex-protein
#4
W H Lee, L Y Choong, T H Jin, N N Mon, S Chong, C S Liew, T Putti, S Y Lu, C Harteneck, Y P Lim
TRPV4 belongs to the 'Transient Receptor Potential' (TRP) superfamily. It has been identified to profoundly affect a variety of physiological processes, including nociception, heat sensation and inflammation. Unlike other TRP superfamily channels, its role in cancers are unknown until recently when we reported TRPV4 to be required for cancer cell softness that may promote breast cancer cell extravasation and metastasis. Here, we elucidated the molecular mechanisms mediated by TRPV4 in the metastatic breast cancer cells...
May 22, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28529828/two-pore-channels-and-parkinson-s-disease-where-s-the-link
#5
Pilar Rivero-Ríos, Belén Fernández, Jesús Madero-Pérez, María Romo Lozano, Sabine Hilfiker
Two-pore channels are endolysosomal Ca(2+) release channels involved in proper trafficking to and from those organelles. They are the likely targets for the Ca(2+)-mobilizing messenger NAADP, and are further regulated by a variety of mechanisms including phosphoinositide levels and Rab proteins. As discussed here, recent studies highlight a role for these channels in the pathomechanism(s) underlying Parkinson's disease, with important implications for possible alternative treatment strategies.
June 1, 2016: Messenger
https://www.readbyqxmd.com/read/28529713/gap-junction-structure-unraveled-but-not-fully-revealed
#6
REVIEW
Eric C Beyer, Viviana M Berthoud
Gap junction channels facilitate the intercellular exchange of ions and small molecules, a process that is critical for the function of many different kinds of cells and tissues. Recent crystal structures of channels formed by one connexin isoform (connexin26) have been determined, and they have been subjected to molecular modeling. These studies have provided high-resolution models to gain insights into the mechanisms of channel conductance, molecular permeability, and gating. The models share similarities, but there are some differences in the conclusions reached by these studies...
2017: F1000Research
https://www.readbyqxmd.com/read/28529474/mir-30b-attenuates-neuropathic-pain-by-regulating-voltage-gated-sodium-channel-nav1-3-in-rats
#7
Songxue Su, Jinping Shao, Qingzan Zhao, Xiuhua Ren, Weihua Cai, Lei Li, Qian Bai, Xuemei Chen, Bo Xu, Jian Wang, Jing Cao, Weidong Zang
Nav1.3 is a tetrodotoxin-sensitive isoform among voltage-gated sodium channels that are closely associated with neuropathic pain. It can be up-regulated following nerve injury, but its biological function remains uncertain. MicroRNAs (miRNAs) are endogenous non-coding RNAs that can regulate post-transcriptional gene expression by binding with their target mRNAs. Using Target Scan software, we discovered that SCN3A is the major target of miR-30b, and we then determined whether miR-30b regulated the expression of Nav1...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28528699/steps-toward-maturation-of-embryonic-stem-cell-derived-cardiomyocytes-by-defined-physical-signals
#8
Nian Shen, Anne Knopf, Claas Westendorf, Udo Kraushaar, Julia Riedl, Hannah Bauer, Simone Pöschel, Shannon Lee Layland, Monika Holeiter, Stefan Knolle, Eva Brauchle, Ali Nsair, Svenja Hinderer, Katja Schenke-Layland
Cardiovascular disease remains a leading cause of mortality and morbidity worldwide. Embryonic stem cell-derived cardiomyocytes (ESC-CMs) may offer significant advances in creating in vitro cardiac tissues for disease modeling, drug testing, and elucidating developmental processes; however, the induction of ESCs to a more adult-like CM phenotype remains challenging. In this study, we developed a bioreactor system to employ pulsatile flow (1.48 mL/min), cyclic strain (5%), and extended culture time to improve the maturation of murine and human ESC-CMs...
May 18, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28528674/sodium-channels-and-venom-peptide-pharmacology
#9
Mathilde R Israel, Bryan Tay, Jennifer R Deuis, Irina Vetter
Venomous animals including cone snails, spiders, scorpions, anemones, and snakes have evolved a myriad of components in their venoms that target the opening and/or closing of voltage-gated sodium channels to cause devastating effects on the neuromuscular systems of predators and prey. These venom peptides, through design and serendipity, have not only contributed significantly to our understanding of sodium channel pharmacology and structure, but they also represent some of the most phyla- and isoform-selective molecules that are useful as valuable tool compounds and drug leads...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28528673/acid-sensing-ion-channel-pharmacology-past-present-and-future-%C3%A2
#10
Lachlan D Rash
pH is one of the most strictly controlled parameters in mammalian physiology. An extracellular pH of ~7.4 is crucial for normal physiological processes, and perturbations to this have profound effects on cell function. Acidic microenvironments occur in many physiological and pathological conditions, including inflammation, bone remodeling, ischemia, trauma, and intense synaptic activity. Cells exposed to these conditions respond in different ways, from tumor cells that thrive to neurons that are either suppressed or hyperactivated, often fatally...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28528672/physiology-and-pharmacology-of-ryanodine-receptor-calcium-release-channels
#11
Angela F Dulhunty, Philip G Board, Nicole A Beard, Marco G Casarotto
Ryanodine receptor (RyR) ion channels are essential for skeletal and cardiac muscle function. Their knockout leads to perinatal death from respiratory and cardiac failure. Acquired changes or mutations in the protein cause debilitating skeletal myopathy and cardiac arrhythmia which can be deadly. Knowledge of the pharmacology of RyR channels is central to developing effective and specific treatments of these myopathies. The ion channel is a >2.2MDa homotetamer with distinct structural and functional characteristics giving rise to a myriad of regulatory sites that are potential therapeutic targets...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28528669/modulation-of-ion-channels-by-cysteine-rich-peptides-from-sequence-to-structure
#12
Mehdi Mobli, Eivind A B Undheim, Lachlan D Rash
Venom peptides are natural ligands of ion channels and have been used extensively in pharmacological characterization of various ion channels and receptors. In this chapter, we survey all known venom peptide ion-channel modulators. Our survey reveals that the majority of venom peptides characterized to date target voltage-gated sodium or potassium channels. We further find that the majority of these peptides are found in scorpion and spider venoms. We discuss the influence of the pharmacological tools available in biasing discovery and the classical "toxin-to-sequence" approach to venom peptide biodiscovery...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28528666/role-of-nonneuronal-trpv4-signaling-in-inflammatory-processes
#13
Pradeep Rajasekhar, Daniel P Poole, Nicholas A Veldhuis
Transient receptor potential (TRP) ion channels are important signaling components in nociceptive and inflammatory pathways. This is attributed to their ability to function as polymodal sensors of environmental stimuli (chemical and mechanical) and as effector molecules in receptor signaling pathways. TRP vanilloid 4 (TRPV4) is a nonselective cation channel that is activated by multiple endogenous stimuli including shear stress, membrane stretch, and arachidonic acid metabolites. TRPV4 contributes to many important physiological processes and dysregulation of its activity is associated with chronic conditions of metabolism, inflammation, peripheral neuropathies, musculoskeletal development, and cardiovascular regulation...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28527921/drug-induced-fatal-arrhythmias-acquired-long-qt-and-brugada-syndromes
#14
REVIEW
Isik Turker, Tomohiko Ai, Hideki Itoh, Minoru Horie
Since the early 1990s, the concept of primary "inherited" arrhythmia syndromes or ion channelopathies has evolved rapidly as a result of revolutionary progresses made in molecular genetics. Alterations in genes coding for membrane proteins such as ion channels or their associated proteins responsible for the generation of cardiac action potentials (AP) have been shown to cause specific malfunctions which eventually lead to cardiac arrhythmias. These arrhythmic disorders include congenital long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, short QT syndrome, progressive cardiac conduction disease, etc...
May 17, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28527849/role-of-piezo-channels-in-ultrasound-stimulated-dental-stem-cells
#15
Qianhua Gao, Paul R Cooper, A Damien Walmsley, Ben A Scheven
INTRODUCTION: Piezo1 and Piezo2 are mechanosensitive membrane ion channels. We hypothesized that Piezo proteins may play a role in transducing ultrasound-associated mechanical signals and activate downstream mitogen-activated protein kinase (MAPK) signaling processes in dental cells. In this study, the expression and role of Piezo channels were investigated in dental pulp stem cells (DPSCs) and periodontal ligament stem cells (PDLSCs) after treatment with low-intensity pulsed ultrasound (LIPUS)...
May 17, 2017: Journal of Endodontics
https://www.readbyqxmd.com/read/28526784/trpv4-mediates-the-calcium-influx-required-for-flightless-non-muscle-myosin-interaction-and-collagen-remodeling
#16
P D Arora, M Di Gregorio, P He, C A McCulloch
Collagen remodeling by phagocytosis requires cell extension formation, which in turn involves interaction of the actin binding protein Flightless I (FliI) with non-muscle myosin IIA (NMMIIA) at cell-matrix adhesion sites. As Ca(2+) plays a central role in controlling actomyosin-dependent functions, we examined how Ca(2+) controls the generation of cell extensions and collagen remodeling. Ratio fluorimetry demonstrated localized Ca(2+) influx at extensions of fibroblasts. Western Blotting and qPCR showed high expression levels of the Ca(2+)-permeable, Transient Receptor Potential Vanilloid-4 (TRPV4) channel, which co-immunoprecipitated with β1 integrin and localized to adhesions...
May 19, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28526746/region-specific-proteolysis-differentially-regulates-type-1-inositol-1-4-5-trisphosphate-receptor-activity
#17
Liwei Wang, Larry E Wagner, Kamil J Alzayady, David I Yule
The inositol 1,4,5 trisphosphate receptor (IP3R) is an intracellular Ca2+ release channel expressed predominately on the membranes of the endoplasmic reticulum. IP3R1 can be cleaved by caspase or calpain into at least two receptor fragments. However, the functional consequences of receptor fragmentation are poorly understood. Our previous work has demonstrated that IP3R1 channels, formed following either enzymatic fragmentation or expression of the corresponding complementary polypeptide chains, retain tetrameric architecture and are still activated by IP3 binding, despite the loss of peptide continuity...
May 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28526717/major-contribution-of-the-3-6-7-class-of-trpc-channels-to-myocardial-ischemia-reperfusion-and-cellular-hypoxia-reoxygenation-injuries
#18
Xiju He, Shoutian Li, Benju Liu, Sebastian Susperreguy, Karina Formoso, Jinghong Yao, Jinsong Kang, Anbing Shi, Lutz Birnbaumer, Yanhong Liao
The injury phase after myocardial infarcts occurs during reperfusion and is a consequence of calcium release from internal stores combined with calcium entry, leading to cell death by apoptopic and necrotic processes. The mechanism(s) by which calcium enters cells has(ve) not been identified. Here, we identify canonical transient receptor potential channels (TRPC) 3 and 6 as the cation channels through which most of the damaging calcium enters cells to trigger their death, and we describe mechanisms activated during the injury phase...
May 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28526610/11-12-epoxyeicosatrienoic-acid-11-12-eet-reduces-excitability-and-excitatory-transmission-in-the-hippocampus
#19
Nandkishor K Mule, Anette C Orjuela Leon, John R Falck, Michael Arand, Anne Marowsky
Recent studies suggest a role for the arachidonic acid-derived epoxyeicosatrienoic acids (EETs) in attenuating epileptic seizures. However, their effect on neurotransmission has never been investigated in detail. Here, we studied how 11,12- and 14,15 EET affect excitability and excitatory neurotransmission in mouse hippocampus. 11,12 EET (2 μM), but not 14,15 EET (2 μM), induced the opening of a hyperpolarizing K(+) conductance in CA1 pyramidal cells. This action could be blocked by BaCl2, the G protein blocker GDPβ-S and the GIRK1/4 blocker tertiapin Q and the channel was thus identified as a GIRK channel...
May 16, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28526583/the-connexin-43-c-terminus-a-tail-of-many-tales
#20
REVIEW
Edward Leithe, Marc Mesnil, Trond Aasen
Connexins are chordate gap junction channel proteins that, by enabling direct communication between the cytosols of adjacent cells, create a unique cell signalling network. Gap junctional intercellular communication (GJIC) has important roles in controlling cell growth and differentiation and in tissue development and homeostasis. Moreover, several non-canonical connexin functions unrelated to GJIC have been discovered. Of the 21 members of the human connexin family, connexin 43 (Cx43) is the most widely expressed and studied...
May 16, 2017: Biochimica et Biophysica Acta
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