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Quan Ke Thai, Dung Anh Chung, Hoang-Dung Tran
BACKGROUND: Canine and wolf mitochondrial DNA haplotypes, which can be used for forensic or phylogenetic analyses, have been defined in various schemes depending on the region analyzed. In recent studies, the 582 bp fragment of the HV1 region is most commonly used. 317 different canine HV1 haplotypes have been reported in the rapidly growing public database GenBank. These reported haplotypes contain several inconsistencies in their haplotype information. To overcome this issue, we have developed a Canis mtDNA HV1 database...
June 26, 2017: BMC Genetics
Takafumi Kawai, Yoshifumi Okochi, Tomohiko Ozaki, Yoshio Imura, Schuichi Koizumi, Maya Yamazaki, Manabu Abe, Kenji Sakimura, Toshihide Yamashita, Yasushi Okamura
It has been established that voltage-gated proton channels (VSOP/Hv1), encoded by Hvcn1, support reactive oxygen species (ROS) production in phagocytic activities of neutrophils (El Chemaly et al. 2010) and antibody production in B lymphocytes (Capasso et al. 2010). VSOP/Hv1 is a potential therapeutic target for brain ischemia, since Hvcn1 deficiency reduces microglial ROS production and protects brain from neuronal damage (Wu et al. 2012). In the present study, we report that VSOP/Hv1 has paradoxical suppressive role in ROS production in microglia...
June 19, 2017: Journal of Neurochemistry
Agustín Asuaje, Pedro Martín, Nicolás Enrique, Leandro Agustín Díaz Zegarra, Paola Smaldini, Guillermo Docena, Verónica Milesi
An established characteristic of neoplastic cells is their metabolic reprogramming, known as the Warburg effect, with greater reliance on energetically less efficient pathways (such as glycolysis and pentose phosphate shunt) compared with oxidative phosphorylation. This results in an overproduction of acidic species that must be extruded to maintain intracellular homeostasis. We recently described that blocking the proton currents in leukemic cells mediated by Hv1 ion channels triggers a marked intracellular acidification and apoptosis induction...
May 17, 2017: Channels
Raha Abedini, Farzan GhaneGolmohammadi, Reihaneh PishkamRad, Ehsan Pourabed, Ahad Jafarnezhad, Zahra-Sadat Shobbar, Maryam Shahbazi
Dehydrins, an important group of late embryogenesis abundant proteins, accumulate in response to dehydration stresses and play protective roles under stress conditions. Herein, phylogenetic analysis of the dehydrin family was performed using the protein sequences of 108 dehydrins obtained from 14 plant species based on plant taxonomy and protein subclasses. Sub-cellular localization and phosphorylation sites of these proteins were also predicted. The protein features distinguishing these dehydrins categories were identified using various attribute weighting and decision tree analyses...
July 2017: Journal of Plant Research
N Badenco, C Chong-Nguyen, C Maupain, C Himbert, G Duthoit, X Waintraub, T Chastre, E Gandjbakhch, F Hidden-Lucet, P Le Prince, J-P Collet, R Frank
BACKGROUND: Atrioventricular block (AVB) is common after transcatheter aortic valve replacement (TAVR) and permanent pacemaker (PPM) implantation is needed in up to 30% of patients. Main predictors of long term AVB are electrocardiographic. The purpose of this study is to assess the prognostic value of serial HV intervals measured before and after TAVR to shorten the timing of PPM implantation. METHODS: His bundle recordings were performed before (HV1), immediately after TAVR (HV2) and at day 2 for Edwards Sapien (ES) and 5 for Medtronic CoreValve (CV) (HV3)...
February 10, 2017: International Journal of Cardiology
Juan D Rodriguez, Saddef Haq, Tsvetan Bachvaroff, Kristine F Nowak, Scott J Nowak, Deri Morgan, Vladimir V Cherny, Maredith M Sapp, Steven Bernstein, Andrew Bolt, Thomas E DeCoursey, Allen R Place, Susan M E Smith
In 1972, J. Woodland Hastings and colleagues predicted the existence of a proton selective channel (HV1) that opens in response to depolarizing voltage across the vacuole membrane of bioluminescent dinoflagellates and conducts protons into specialized luminescence compartments (scintillons), thereby causing a pH drop that triggers light emission. HV1 channels were subsequently identified and demonstrated to have important functions in a multitude of eukaryotic cells. Here we report a predicted protein from Lingulodinium polyedrum that displays hallmark properties of bona fide HV1, including time-dependent opening with depolarization, perfect proton selectivity, and characteristic ΔpH dependent gating...
2017: PloS One
Jiwon Kim, Jin-Ho Song
Microglial NADPH oxidase is a major source of toxic reactive oxygen species produced during chronic neuroinflammation. Voltage-gated proton channel (HV1) functions to maintain the intense activity of NADPH oxidase, and channel inhibition alleviates the pathology of neurodegenerative diseases such as ischemic stroke and multiple sclerosis associated with oxidative neuroinflammation. Antagonists of histamine H1 receptors have beneficial effects against microglia-mediated oxidative stress and neurotoxicity. We examined the effects of the H1 antihistamines, diphenhydramine and chlorpheniramine, on proton currents in BV2 microglial cells recorded using the whole-cell patch clamp technique...
March 5, 2017: European Journal of Pharmacology
Agustín Asuaje, Paola Smaldini, Pedro Martín, Nicolás Enrique, Alejandro Orlowski, Ernesto A Aiello, Carlos Gonzalez León, Guillermo Docena, Verónica Milesi
Cellular energetic deregulation is widely known to produce an overproduction of acidic species in cancer cells. This acid overload must be counterbalanced with a high rate of H(+) extrusion to maintain cell viability. In this sense, many H(+) transporters have been reported to be crucial for cell survival and proposed as antineoplastic target. By the way, voltage-gated proton channels (Hv1) mediate highly selective H(+) outward currents, capable to compensate acid burden in brief periods of time. This structure is canonically described acting as NADPH oxidase counterbalance in reactive oxygen species production...
December 24, 2016: Pflügers Archiv: European Journal of Physiology
Eleonora Gianti, Lucie Delemotte, Michael L Klein, Vincenzo Carnevale
Hv1 is a transmembrane four-helix bundle that transports protons in a voltage-controlled manner. Its crucial role in many pathological conditions, including cancer and ischemic brain damage, makes Hv1 a promising drug target. Starting from the recently solved crystal structure of Hv1, we used structural modeling and molecular dynamics simulations to characterize the channel's most relevant conformations along the activation cycle. We then performed computational docking of known Hv1 inhibitors, 2-guanidinobenzimidazole (2GBI) and analogs...
December 27, 2016: Proceedings of the National Academy of Sciences of the United States of America
Thomas K Berger, David M Fußhöller, Normann Goodwin, Wolfgang Bönigk, Astrid Müller, Nasim Dokani Khesroshahi, Christoph Brenker, Dagmar Wachten, Eberhard Krause, U Benjamin Kaupp, Timo Strünker
KEY POINTS: In human sperm, proton flux across the membrane is controlled by the voltage-gated proton channel Hv1. We show that sperm harbour both Hv1 and an N-terminally cleaved isoform termed Hv1Sper. The pH-control of Hv1Sper and Hv1 is distinctively different. Hv1Sper and Hv1 can form heterodimers that combine features of both constituents. Cleavage and heterodimerization of Hv1 might represent an adaptation to the specific requirements of pH control in sperm. ABSTRACT: In human sperm, the voltage-gated proton channel Hv1 controls the flux of protons across the flagellar membrane...
March 1, 2017: Journal of Physiology
Siri C van Keulen, Eleonora Gianti, Vincenzo Carnevale, Michael L Klein, Ursula Rothlisberger, Lucie Delemotte
Hv1s are ubiquitous highly selective voltage-gated proton channels involved in male fertility, immunology, and the invasiveness of certain forms of breast cancer. The mechanism of proton extrusion in Hv1 is not yet understood, while it constitutes the first step toward the design of high-affinity drugs aimed at this important pharmacological target. In this contribution, we explore the details of the mechanism via an integrative approach, using classical and QM/MM molecular dynamics simulations of a monomeric hHv1 model...
April 20, 2017: Journal of Physical Chemistry. B
Medha M Pathak, Truc Tran, Liang Hong, Béla Joós, Catherine E Morris, Francesco Tombola
The voltage-gated proton channel, Hv1, is expressed in tissues throughout the body and plays important roles in pH homeostasis and regulation of NADPH oxidase. Hv1 operates in membrane compartments that experience strong mechanical forces under physiological or pathological conditions. In microglia, for example, Hv1 activity is potentiated by cell swelling and causes an increase in brain damage after stroke. The channel complex consists of two proton-permeable voltage-sensing domains (VSDs) linked by a cytoplasmic coiled-coil domain...
November 2016: Journal of General Physiology
Frank V Marcoline, Yoichi Ishida, Joseph A Mindell, Smita Nayak, Michael Grabe
Bone resorption by osteoclasts occurs through the creation of a sealed extracellular compartment (ECC), or pit, adjacent to the bone that is subsequently acidified through a complex biological process. The low pH of the pit dissolves the bone mineral and activates acid proteases that further break down the bone matrix. There are many ion channels, transporters, and soluble proteins involved in osteoclast mediated resorption, and in the past few years, there has been an increased understanding of the identity and properties of some key proteins such as the ClC-7 Cl(-)/H(+) antiporter and the HV1 proton channel...
December 2016: Bone
Feng Qiu, Adam Chamberlin, Briana M Watkins, Alina Ionescu, Marta Elena Perez, Rene Barro-Soria, Carlos González, Sergei Y Noskov, H Peter Larsson
Voltage-gated proton (Hv1) channels are involved in many physiological processes, such as pH homeostasis and the innate immune response. Zn(2+) is an important physiological inhibitor of Hv1. Sperm cells are quiescent in the male reproductive system due to Zn(2+) inhibition of Hv1 channels, but become active once introduced into the low-Zn(2+)-concentration environment of the female reproductive tract. How Zn(2+) inhibits Hv1 is not completely understood. In this study, we use the voltage clamp fluorometry technique to identify the molecular mechanism of Zn(2+) inhibition of Hv1...
October 4, 2016: Proceedings of the National Academy of Sciences of the United States of America
Souhei Sakata, Nana Miyawaki, Thomas J McCormack, Hiroki Arima, Akira Kawanabe, Nurdan Özkucur, Tatsuki Kurokawa, Yuka Jinno, Yuichiro Fujiwara, Yasushi Okamura
The voltage-gated proton channel, Hv1, is expressed in blood cells, airway epithelium, sperm and microglia, playing important roles in diverse biological contexts including phagocytosis or sperm maturation through its regulation of membrane potential and pH. The gene encoding Hv1, HVCN1, is widely found across many species and is also conserved in unicellular organisms such as algae or dinoflagellates where Hv1 plays role in calcification or bioluminescence. Voltage-gated proton channels exhibit a large variation of activation rate among different species...
December 2016: Biochimica et Biophysica Acta
L S Barrientos, J A Crespi, A Fameli, D M Posik, H Morales, P Peral García, G Giovambattista
Dog fecal samples were collected at the crime scene and from the shoes of the suspect to see whether they could be linked. DNA was genotyped using a 145bp fragment containing a 60bp hotspot region of the mitochondrial DNA (mtDNA) control region. Once the species origin was identified, sequences were aligned with the 23 canine haplotypes defined, showing that evidence and reference had 100% identity with haplotype 5. The frequency of haplotype 5 and the exclusion power of the reference population were 0.056 and 0...
September 2016: Legal Medicine
Aaron L Randolph, Younes Mokrab, Ashley L Bennett, Mark Sp Sansom, Ian Scott Ramsey
The Hv1 proton channel is evidently unique among voltage sensor domain proteins in mediating an intrinsic 'aqueous' H(+) conductance (GAQ). Mutation of a highly conserved 'gating charge' residue in the S4 helix (R1H) confers a resting-state H(+) 'shuttle' conductance (GSH) in VGCs and Ci VSP, and we now report that R1H is sufficient to reconstitute GSH in Hv1 without abrogating GAQ. Second-site mutations in S3 (D185A/H) and S4 (N4R) experimentally separate GSH and GAQ gating, which report thermodynamically distinct initial and final steps, respectively, in the Hv1 activation pathway...
August 30, 2016: ELife
Dai-Shi Tian, Chun-Yu Li, Chuan Qin, Madhuvika Murugan, Long-Jun Wu, Jun-Li Liu
Microglia become activated during cerebral ischemia and exert pro-inflammatory or anti-inflammatory role dependent of microglial polarization. NADPH oxidase (NOX)-dependent reactive oxygen species (ROS) production in microglia plays an important role in neuronal damage after ischemic stroke. Recently, NOX and ROS are consistently reported to participate in the microglial activation and polarization; NOX2 inhibition or suppression of ROS production are shown to shift the microglial polarization from M1 toward M2 state after stroke...
October 2016: Journal of Neurochemistry
Audry Fernández, Amaury Pupo, Karel Mena-Ulecia, Carlos Gonzalez
The pharmacological modulation of the immunosuppressive tumor microenvironment has emerged as a relevant component for cancer therapy. Several approaches aiming to deplete innate and adaptive suppressive populations, to circumvent the impairment in antigen presentation, and to ultimately increase the frequency of activated tumor-specific T cells are currently being explored. In this review, we address the potentiality of targeting the voltage-gated proton channel, Hv1, as a novel strategy to modulate the tumor microenvironment...
September 2016: Molecular Pharmacology
Luisa Ribeiro-Silva, Fernanda Oliveira Queiroz, Annielle Mendes Brito da Silva, Aparecida Emiko Hirata, Manoel Arcisio-Miranda
Solid tumors tend to have a more glycolytic metabolism leading to an accumulation of acidic metabolites in their cytosol, and consequently, their intracellular pH (pHi) turns critically lower if the cells do not handle the acid excess. Recently, it was proposed that the voltage gated proton channels (HV1) can regulate the pHi in several cancers. Here we report the functional expression of voltage gated proton channels in a human glioblastoma multiforme (GBM) cell line, the most common and lethal brain tumor...
July 20, 2016: ACS Chemical Neuroscience
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