keyword
https://read.qxmd.com/read/37677148/a-commentary-on-the-inhibition-of-human-tpc2-channel-by-the-natural-flavonoid-naringenin-methods-experiments-and-ideas
#1
REVIEW
Velia Minicozzi, Tianwen Qi, Antonella Gradogna, Marina Pozzolini, Stefan Milenkovic, Antonio Filippini, Matteo Ceccarelli, Armando Carpaneto
Human endo-lysosomes possess a class of proteins called TPC channels on their membrane, which are essential for proper cell functioning. This protein family can be functionally studied by expressing them in plant vacuoles. Inhibition of hTPC activity by naringenin, one of the main flavonoids present in the human diet, has the potential to be beneficial in severe human diseases such as solid tumor development, melanoma, and viral infections. We attempted to identify the molecular basis of the interaction between hTPC2 and naringenin, using ensemble docking on molecular dynamics (MD) trajectories, but the specific binding site remains elusive, posing a challenge that could potentially be addressed in the future by increased computational power in MD and the combined use of microscopy techniques such as cryo-EM...
January 1, 2023: Biomolecular Concepts
https://read.qxmd.com/read/37676514/electrophysiology-and-fluorescence-to-investigate-cation-channels-and-transporters-in-isolated-plant-vacuoles
#2
REVIEW
Antonella Gradogna, Armando Carpaneto
The plant vacuole plays a fundamental role in cell homeostasis. The successful application of patch-clamp technique on isolated vacuoles allows the determination of the functional characteristics of tonoplast ion channels and transporters. The parallel use of a sensor-based fluorescence approach capable of detecting changes in calcium and proton concentrations opens up new possibilities for investigation. In excised patch, the presence of fura-2 in the vacuolar solution reveals the direct permeation of calcium in plant TPC channels...
October 1, 2022: Stress Biol
https://read.qxmd.com/read/36139875/design-characterization-and-anticancer-and-antimicrobial-activities-of-mucoadhesive-oral-patches-loaded-with-usnea-barbata-l-f-h-wigg-ethanol-extract-f-ube-hpmc
#3
JOURNAL ARTICLE
Violeta Popovici, Elena Matei, Georgeta Camelia Cozaru, Laura Bucur, Cerasela Elena Gîrd, Verginica Schröder, Emma Adriana Ozon, Mirela Adriana Mitu, Adina Magdalena Musuc, Simona Petrescu, Irina Atkinson, Adriana Rusu, Raul-Augustin Mitran, Mihai Anastasescu, Aureliana Caraiane, Dumitru Lupuliasa, Mariana Aschie, Eugen Dumitru, Victoria Badea
The oral cavity's common pathologies are tooth decay, periodontal disease, and oral cancer; oral squamous cell carcinoma (OSCC) is the most frequent oral malignancy, with a high mortality rate. Our study aims to formulate, develop, characterize, and pharmacologically investigate the oral mucoadhesive patches (F-UBE-HPMC) loaded with Usnea barbata (L.) F.H. Wigg dry ethanol extract (UBE), using HPMC K100 as a film-forming polymer. Each patch contains 312 µg UBE, with a total phenolic content (TPC) of 178.849 µg and 33...
September 13, 2022: Antioxidants (Basel, Switzerland)
https://read.qxmd.com/read/35902437/naadp-dependent-tpc-current
#4
JOURNAL ARTICLE
Qiaochu Wang, Michael X Zhu
Two-pore channels, TPC1 and TPC2, are Ca2+ - and Na+ -permeable cation channels expressed on the membranes of endosomes and lysosomes in nearly all mammalian cells. These channels have been implicated in Ca2+ signaling initiated from the endolysosomes, vesicular trafficking, cellular metabolism, macropinocytosis, and viral infection. Although TPCs have been shown to mediate Ca2+ release from acidic organelles in response to NAADP (nicotinic acid adenine dinucleotide phosphate), the most potent Ca2+ mobilizing messenger, questions remain whether NAADP is a direct ligand of these channels...
July 29, 2022: Handbook of Experimental Pharmacology
https://read.qxmd.com/read/35902436/expanding-the-toolbox-novel-modulators-of-endolysosomal-cation-channels
#5
JOURNAL ARTICLE
Susanne Rautenberg, Marco Keller, Charlotte Leser, Cheng-Chang Chen, Franz Bracher, Christian Grimm
Functional characterization of endolysosomal ion channels is challenging due to their intracellular location. With recent advances in endolysosomal patch clamp technology, it has become possible to directly measure ion channel currents across endolysosomal membranes. Members of the transient receptor potential (TRP) cation channel family, namely the endolysosomal TRPML channels (TRPML1-3), also called mucolipins, as well as the distantly related two-pore channels (TPCs) have recently been characterized in more detail with endolysosomal patch clamp techniques...
July 29, 2022: Handbook of Experimental Pharmacology
https://read.qxmd.com/read/35879579/the-plant-vacuole-as-heterologous-system-to-characterize-the-functional-properties-of-tpc-channels
#6
JOURNAL ARTICLE
P Dietrich, A Gradogna, A Carpaneto
Human TPC channels are an emerging family of intracellular proteins fundamental for cell physiology and involved in various severe pathologies. Their localization in the membranes of endo-lysosomes, intracellular compartments of submicrometric dimensions, makes their study difficult with usual electrophysiological techniques. In this work, we show how the plant vacuole, a versatile organelle that can occupy up to 90% of the volume in mature plant cells, can be used as a heterologous system of expression for functional characterization...
July 26, 2022: Handbook of Experimental Pharmacology
https://read.qxmd.com/read/35805090/the-three-two-pore-channel-subtypes-from-rabbit-exhibit-distinct-sensitivity-to-phosphoinositides-voltage-and-extracytosolic-ph
#7
JOURNAL ARTICLE
Xinghua Feng, Jian Xiong, Weijie Cai, Jin-Bin Tian, Michael X Zhu
Two pore channels (TPCs) are implicated in vesicle trafficking, virus infection, and autophagy regulation. As Na+ - or Ca2+ -permeable channels, TPCs have been reported to be activated by NAADP, PI(3,5)P2 , and/or high voltage. However, a comparative study on the function and regulation of the three mammalian TPC subtypes is currently lacking. Here, we used the electrophysiological recording of enlarged endolysosome vacuoles, inside-out and outside-out membrane patches to examine the three TPCs of rabbit ( Oryctolagus cuniculus , or Oc ) heterologously expressed in HEK293 cells...
June 23, 2022: Cells
https://read.qxmd.com/read/34936705/functional-analyses-of-the-two-distinctive-types-of-two-pore-channels-tpcs-and-the-slow-vacuolar-channel-in-marchantia-polymorpha
#8
JOURNAL ARTICLE
Kenji Hashimoto, Mateusz Koselski, Shoko Tsuboyama, Halina Dziubinska, Kazimierz Trębacz, Kazuyuki Kuchitsu
The two-pore channel (TPC) family is widely conserved in eukaryotes. Many vascular plants, including Arabidopsis and rice, possess a single TPC gene which functions as a slow vacuolar (SV) channel-voltage-dependent cation-permeable channel located in the vacuolar membrane (tonoplast). On the other hand, a liverwort Marchantia polymorpha genome encodes three TPC homologs: MpTPC1 is similar to TPCs in vascular plants (type 1 TPC), while MpTPC2 and MpTPC3 are classified into a distinctive group (type 2 TPC). Phylogenetic analysis suggested that the type 2 TPC emerged before the land colonization in plant evolution and was lost in vascular plants and hornworts...
December 22, 2021: Plant & Cell Physiology
https://read.qxmd.com/read/29486387/modulation-of-calcium-and-potassium-permeation-in-plant-tpc-channels
#9
JOURNAL ARTICLE
Armando Carpaneto, Antonella Gradogna
Plant two-pore channels (TPCs) are non-selective cation channels permeable both to monovalent potassium and divalent calcium. We previously developed a technique that allowed the simultaneous determination of the fluxes of these two ions across the channel by a combined use of patch-clamp and fluorescence. In this paper we studied how potassium and calcium fluxes were influenced by modification of cytosolic concentrations of K+ and Ca2+ . A decrease in cytosolic calcium from 2 to 0.5 mM led to a shift of the activation curve of about +60 mV; although at positive potentials currents were very similar, calcium ion permeation was significantly reduced and the ratio between the total and calcium-mediated current increased about two-fold...
May 2018: Biophysical Chemistry
https://read.qxmd.com/read/25883134/telomere-associated-proteins-add-deoxynucleotides-to-terminal-proteins-during-replication-of-the-telomeres-of-linear-chromosomes-and-plasmids-in-streptomyces
#10
JOURNAL ARTICLE
Chien-Chin Yang, Shu-Min Tseng, Carton W Chen
Typical telomeres of linear chromosomes and plasmids of soil bacteria Streptomyces consist of tightly packed palindromic sequences with a terminal protein ('TP') covalently attached to the 5' end of the DNA. Replication of these linear replicons is initiated internally and proceeds bidirectionally toward the telomeres, which leaves single-strand overhangs at the 3' ends. These overhangs are filled by DNA synthesis using the TPs as the primers ('end patching'). The gene encoding for typical TP, tpg, forms an operon with tap, encoding an essential telomere-associated protein, which binds TP and the secondary structures formed by the 3' overhangs...
July 27, 2015: Nucleic Acids Research
https://read.qxmd.com/read/25872774/expression-of-ca%C3%A2-%C3%A2-%C2%BA-permeable-two-pore-channels-rescues-naadp-signalling-in-tpc-deficient-cells
#11
JOURNAL ARTICLE
Margarida Ruas, Lianne C Davis, Cheng-Chang Chen, Anthony J Morgan, Kai-Ting Chuang, Timothy F Walseth, Christian Grimm, Clive Garnham, Trevor Powell, Nick Platt, Frances M Platt, Martin Biel, Christian Wahl-Schott, John Parrington, Antony Galione
The second messenger NAADP triggers Ca(2+) release from endo-lysosomes. Although two-pore channels (TPCs) have been proposed to be regulated by NAADP, recent studies have challenged this. By generating the first mouse line with demonstrable absence of both Tpcn1 and Tpcn2 expression (Tpcn1/2(-/-)), we show that the loss of endogenous TPCs abolished NAADP-dependent Ca(2+) responses as assessed by single-cell Ca(2+) imaging or patch-clamp of single endo-lysosomes. In contrast, currents stimulated by PI(3,5)P2 were only partially dependent on TPCs...
July 2, 2015: EMBO Journal
https://read.qxmd.com/read/25512843/impact-of-global-warming-at-the-range-margins-phenotypic-plasticity-and-behavioral-thermoregulation-will-buffer-an-endemic-amphibian
#12
JOURNAL ARTICLE
Manuel Ruiz-Aravena, Avia Gonzalez-Mendez, Sergio A Estay, Juan D Gaitán-Espitia, Ismael Barria-Oyarzo, José L Bartheld, Leonardo D Bacigalupe
When dispersal is not an option to evade warming temperatures, compensation through behavior, plasticity, or evolutionary adaptation is essential to prevent extinction. In this work, we evaluated whether there is physiological plasticity in the thermal performance curve (TPC) of maximum jumping speed in individuals acclimated to current and projected temperatures and whether there is an opportunity for behavioral thermoregulation in the desert landscape where inhabits the northernmost population of the endemic frog Pleurodema thaul...
December 2014: Ecology and Evolution
https://read.qxmd.com/read/25072391/decoding-and-encoding-of-visual-patterns-using-magnetoencephalographic-data-represented-in-manifolds
#13
JOURNAL ARTICLE
Po-Chih Kuo, Yong-Sheng Chen, Li-Fen Chen, Jen-Chuen Hsieh
Visual decoding and encoding are crucial aspects in investigating the representation of visual information in the human brain. This paper proposes a bidirectional model for decoding and encoding of visual stimulus based on manifold representation of the temporal and spatial information extracted from magnetoencephalographic data. In the proposed decoding process, principal component analysis is applied to extract temporal principal components (TPCs) from the visual cortical activity estimated by a beamforming method...
November 15, 2014: NeuroImage
https://read.qxmd.com/read/24770793/the-phosphoinositide-pi-3-5-p%C3%A2-mediates-activation-of-mammalian-but-not-plant-tpc-proteins-functional-expression-of-endolysosomal-channels-in-yeast-and-plant-cells
#14
JOURNAL ARTICLE
Anna Boccaccio, Joachim Scholz-Starke, Shin Hamamoto, Nina Larisch, Margherita Festa, Paul Vijay Kanth Gutla, Alex Costa, Petra Dietrich, Nobuyuki Uozumi, Armando Carpaneto
Two-pore channel proteins (TPC) encode intracellular ion channels in both animals and plants. In mammalian cells, the two isoforms (TPC1 and TPC2) localize to the endo-lysosomal compartment, whereas the plant TPC1 protein is targeted to the membrane surrounding the large lytic vacuole. Although it is well established that plant TPC1 channels activate in a voltage- and calcium-dependent manner in vitro, there is still debate on their activation under physiological conditions. Likewise, the mode of animal TPC activation is heavily disputed between two camps favoring as activator either nicotinic acid adenine dinucleotide phosphate (NAADP) or the phosphoinositide PI(3,5)P₂...
November 2014: Cellular and Molecular Life Sciences: CMLS
https://read.qxmd.com/read/24067506/targeting-sonic-hedgehog-associated-medulloblastoma-through-inhibition-of-aurora-and-polo-like-kinases
#15
JOURNAL ARTICLE
Shirley L Markant, Lourdes Adriana Esparza, Jesse Sun, Kelly L Barton, Lisa M McCoig, Gerald A Grant, John R Crawford, Michael L Levy, Paul A Northcott, David Shih, Marc Remke, Michael D Taylor, Robert J Wechsler-Reya
Medulloblastoma is the most common malignant brain tumor in children. Although aggressive surgery, radiation, and chemotherapy have improved outcomes, survivors suffer severe long-term side effects, and many patients still succumb to their disease. For patients whose tumors are driven by mutations in the sonic hedgehog (SHH) pathway, SHH antagonists offer some hope. However, many SHH-associated medulloblastomas do not respond to these drugs, and those that do may develop resistance. Therefore, more effective treatment strategies are needed for both SHH and non-SHH-associated medulloblastoma...
October 15, 2013: Cancer Research
https://read.qxmd.com/read/23105130/modulation-of-plant-tpc-channels-by-polyunsaturated-fatty-acids
#16
JOURNAL ARTICLE
Paul Vijay Kanth Gutla, Anna Boccaccio, Alexis De Angeli, Franco Gambale, Armando Carpaneto
Polyunsaturated fatty acids (PUFAs) are powerful modulators of several animal ion channels. It is shown here that PUFAs strongly affect the activity of the Slow Vacuolar (SV) channel encoded by the plant TPC1 gene. The patch-clamp technique was applied to isolated vacuoles from carrot taproots and Arabidopsis thaliana mesophyll cells and arachidonic acid (AA) was chosen as a model molecule for PUFAs. Our study was extended to different PUFAs including the endogenous alpha-linolenic acid (ALA). The addition of micromolar concentrations of AA reversibly inhibited the SV channel decreasing the maximum open probability and shifting the half activation voltage to positive values...
October 2012: Journal of Experimental Botany
https://read.qxmd.com/read/21109537/linear-streptomyces-plasmids-form-superhelical-circles-through-interactions-between-their-terminal-proteins
#17
JOURNAL ARTICLE
Hsiu-Hui Tsai, Chih-Hung Huang, Ingrid Tessmer, Dorothy A Erie, Carton W Chen
Linear chromosomes and linear plasmids of Streptomyces possess covalently bound terminal proteins (TPs) at the 5' ends of their telomeres. These TPs are proposed to act as primers for DNA synthesis that patches the single-stranded gaps at the 3' ends during replication. Most ('archetypal') Streptomyces TPs (designated Tpg) are highly conserved in size and sequence. In addition, there are a number of atypical TPs with heterologous sequences and sizes, one of which is Tpc that caps SCP1 plasmid of Streptomyces coelicolor...
March 2011: Nucleic Acids Research
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