Article
Neurosciences
Eric A. Bancroft, Martha De La Mora, Gauri Pandey, Sara M. Zarate, Rahul Srinivasan
Summary: Parkinson's disease is associated with increased levels of S100B and its overexpression accelerates the loss of dopaminergic neurons. The study found that S100B can alter the activity of dopamine neurons, providing important insights into the pathophysiology of early Parkinson's disease.
Article
Food Science & Technology
Evelyne Benoit, Sebastien Schlumberger, Jordi Molgo, Makoto Sasaki, Haruhiko Fuwa, Roland Bournaud
Summary: Gambierol inhibits K+ channels in rat fetal adrenomedullary cells, but has no effect on other channels. It does not alter membrane potential or increase catecholamine release events.
Article
Neurosciences
Victoria Gonzalez Sabater, Mark Rigby, Juan Burrone
Summary: In this study, the initiation and propagation of action potentials (APs) along the axon were investigated using genetically encoded voltage indicators (GEVIs) in dissociated hippocampal neurons from rat embryos. It was found that APs became sharper and exhibited greater fidelity as they traveled towards distal axonal domains. Blocking voltage-gated potassium channels (K-v) resulted in an increase in AP width, especially in distal locations, suggesting that higher levels of Kv channel activity in distal axons contribute to maintaining AP fidelity.
JOURNAL OF NEUROSCIENCE
(2021)
Review
Pharmacology & Pharmacy
Ksenia S. Kudryashova, Oksana V. Nekrasova, Mikhail P. Kirpichnikov, Alexey V. Feofanov
Summary: This review discusses the construction of chimeric potassium channels KcsA-Kv1, their applications in studying interactions of pore blockers, and their role in determining molecular basis for high affinity and selectivity of binding of peptide blockers to Kv1 channels.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Cell Biology
Faye L. Styles, Moza M. Al-Owais, Jason L. Scragg, Eulashini Chuntharpursat-Bon, Nishani T. Hettiarachchi, Jonathan D. Lippiat, Aisling Minard, Robin S. Bon, Karen Porter, Piruthivi Sukumar, Chris Peers, Lee D. Roberts
Summary: The Kv1.3 voltage-gated potassium channel drives cellular proliferation by increasing oxidative phosphorylation and generating reactive oxygen species independently of redox balance, mitochondrial membrane potential, or calcium signaling. Reduction of reactive oxygen concentrations inhibits Kv1.3-induced proliferation.
CELL DEATH & DISEASE
(2021)
Review
Endocrinology & Metabolism
Nihal Ozturk, Serkan Uslu, Semir Ozdemir
Summary: Diabetes affects the heart through various mechanisms, including microvascular defects, metabolic abnormalities, and electrophysiological changes, leading to diabetic cardiomyopathy (DCM) which can cause structural and functional changes in the heart. DCM progresses to cause electrical remodeling, left ventricular dysfunction, and heart failure, contributing significantly to arrhythmias and sudden cardiac death in diabetes patients.
WORLD JOURNAL OF DIABETES
(2021)
Article
Biochemistry & Molecular Biology
Sara R. Roig, Silvia Cassinelli, Maria Navarro-Perez, Mireia Perez-Verdaguer, Irene Estadella, Jesusa Capera, Antonio Felipe
Summary: The Kv beta family is a group of modulators that regulate Kv channels, with Kv beta 2.1 clustering into immunological synapses during leukocyte activation. The localization of Kv beta 2.1 is mainly affected by S-acylation and a pair of C-terminal cysteines, and its targeting to lipid raft microdomains is influenced by various stimuli.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Multidisciplinary Sciences
Serap Erdogmus, Axel R. Concepcion, Megumi Yamashita, Ikjot Sidhu, Anthony Y. Tao, Wenyi Li, Pedro P. Rocha, Bonnie Huang, Ralph Garippa, Boram Lee, Amy Lee, Johannes W. Hell, Richard S. Lewis, Murali Prakriya, Stefan Feske
Summary: The regulatory beta subunit of voltage-gated calcium channels regulates T cell function despite no evidence that these channels were functional within T cells during activation.
NATURE COMMUNICATIONS
(2022)
Article
Neurosciences
Elena G. Govorunova, Oleg A. Sineshchekov, Leonid S. Brown, John L. Spudich
Summary: Channelrhodopsins are proteins that guide phototaxis and have applications in optogenetics. This study reports the use of a high-throughput automated patch-clamp platform for the characterization of ChRs, providing a more efficient method than manual patch clamping.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Chemistry, Multidisciplinary
Oliya S. Abdullaeva, Ihor Sahalianov, Malin Silvera Ejneby, Marie Jakesova, Igor Zozoulenko, Sara I. Liin, Eric Daniel Glowacki
Summary: A microfabricated ROS modulation device based on controlled faradaic reactions was developed in this research. The device can generate tunable gradients of peroxide and oxygen concentrations, enabling controlled H2O2 delivery. The prototype devices were tested by modulating human H2O2-sensitive channels to demonstrate the potential of PEDOT as an H2O2 delivery system.
Article
Pharmacology & Pharmacy
Emily Sze-Wan Wong, Rachel Wai-Sum Li, Jingjing Li, Renkai Li, Sai-Wang Seto, Simon Ming-Yuen Lee, George Pak-Heng Leung
Summary: Narirutin induces relaxation in rat mesenteric arteries through mechanisms involving phosphodiesterase inhibition, leading to increased intracellular cAMP, stimulation of endothelial nitric oxide synthase, and activation of voltage-gated potassium channels in vascular smooth muscle cells.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Marcelino Cereijido, Lidia Jimenez, Lorena Hinojosa, Aida Castillo, Jacqueline Martinez-Rendon, Arturo Ponce
Summary: This study reveals a new role for ouabain as a modulator of the expression of voltage-gated potassium channels in epithelial cells, which requires cell-cell contacts.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Adina Stoian, Mircea Stoian, Zoltan Bajko, Smaranda Maier, Sebastian Andone, Roxana Adriana Cioflinc, Anca Motataianu, Laura Barcutean, Rodica Balasa
Summary: Neurological complications are common in hospitalized COVID-19 patients, with autoimmune encephalitis being one of them. COVID-19 infection may trigger an autoimmune response leading to damage in the nervous system. Exploring and understanding this immune-mediated encephalitis is crucial for the management and treatment of COVID-19 patients.
Article
Cardiac & Cardiovascular Systems
Gyeoung-Jin Kang, An Xie, Eunji Kim, Samuel C. Dudley Jr
Summary: This study revealed that myocardial ischemia results in the downregulation of KCNA4 gene expression and the upregulation of miR-448 gene expression. miR-448 binds to a specific region of KCNA4 gene, leading to the decreased expression of KCNA4 and the alteration of normal cardiac action potential. These findings provide insights into the mechanism of miR-448 regulation of KCNA4 expression during ischemia.
Article
Clinical Neurology
Sreerag Othayoth Vasu, Hanoch Kaphzan
Summary: This study demonstrates that inhibiting voltage-gated potassium channels obstructs the tDCS-induced modulation of subthreshold presynaptic vesicle release, and inhibiting Kv1 voltage-gated potassium channels also obstructs the tDCS-induced modulation of action potential waveform at axon terminals.
Article
Food Science & Technology
Sandra Raposo-Garcia, M. Carmen Louzao, Haruhiko Fuwa, Makoto Sasaki, Carmen Vale, Luis M. Botana
Summary: Ciguatoxins are causative compounds of ciguatera fish poisoning and their potency is determined as CTX1B > CTX3B > CTX4A > gambierol > gambiemne > MTX3. The activation voltage of sodium channels is more sensitive in detecting ciguatoxins than their effect on peak sodium current amplitude.
FOOD AND CHEMICAL TOXICOLOGY
(2022)
Article
Chemistry, Medicinal
Maria Carmen Louzao, Natalia Vilarino, Carmen Vale, Celia Costas, Alejandro Cao, Sandra Raposo-Garcia, Mercedes R. Vieytes, Luis M. Botana
Summary: This article discusses the importance of marine phycotoxins and their impact on human health, ecosystems, and the economy. It emphasizes the challenges in setting regulatory limits and conducting monitoring, as well as the demand for universal phycotoxin detectors.
Article
Toxicology
Sandra Raposo-Garcia, Andrea Boente-Juncal, Mercedes Rodriguez-Vieytes, Mercedes Camina, Celia Costas, Alejandro Cao, M. Carmen Louzao, Manuel Cifuentes, Carmen Vale, Luis M. Botana
Summary: Ciguatoxins are marine compounds produced by dinoflagellates that can cause food poisoning. This study investigated the effects of ciguatoxin-related compounds on mice and highlighted the need to reevaluate their in vivo activity. It also emphasized the importance of using standardized procedures and certified reference materials to determine the levels of these environmental contaminants in food.
ARCHIVES OF TOXICOLOGY
(2022)
Article
Food Science & Technology
Celia Costas, M. Carmen Louzao, Sandra Raposo-Garcia, Carmen Vale, Mercedes R. Vieytes, Luis M. Botana
Summary: In this study, the researchers evaluated the effect of Okadaic acid (OA) on diarrhea using mice models. The results showed that OA exposure led to an increase in chloride and sodium concentration in the feces, indicating a secretory diarrhea. However, pre-treatment with cyproheptadine (CPH) attenuated the damage caused by OA in the colon and jejunum. The study identified cellular mechanisms underlying OA-induced diarrhea and highlighted the complex toxicity of this compound.
FOOD AND CHEMICAL TOXICOLOGY
(2022)
Article
Chemistry, Medicinal
Celso Alves, Joana Silva, Susete Pinteus, Romina A. Guedes, Rita C. Guedes, Rebeca Alvarino, Rafaela Freitas, Marcia Goettert, Helena Gaspar, Amparo Alfonso, Maria C. Alpoim, Luis M. Botana, Rui Pedrosa
Summary: This study evaluated the cytotoxic and proteasome inhibitory activities of compounds isolated from Sphaerococcus coronopifolius, with potential as anticancer agents. The compounds showed cytotoxic effects on malignant cell lines and induced DNA damage. They also affected mitochondrial function, phosphatidylserine externalization, Caspase-9 activity, and nuclear morphology. Further studies are needed to fully understand the potential of these compounds for anticancer therapeutics.
Article
Chemistry, Multidisciplinary
Kazuk i Nakazato, Mami Oda, Haruhiko Fuwa
Summary: The total synthesis of (+)-neopeltolide, a potent antiproliferative marine macrolide natural product, was achieved in 11 steps from a commercially available inexpensive material. The 14-membered macrolactone skeleton with a 2,6-cis-substituted tetrahydropyran ring was synthesized using a macrocyclization/trans-annular pyran cyclization strategy. The synthesis of the oxazole-containing side chain was achieved through palladium-catalyzed cross-coupling reactions. Additionally, the total synthesis of (+)-9-epi-neopeltolide was accomplished in 12 steps by stereochemical diversification at the C9 position.
BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN
(2023)
Article
Chemistry, Multidisciplinary
Keisuke Murata, Hirotoshi Mori, Haruhiko Fuwa
Summary: In this study, the application of GIAO NMR chemical shift calculation and DP4-type statistical analyses in the stereochemical assignment of marine macrolide natural products was assessed. The incorrect relative configurations in the originally proposed structures were identified and the effect of cumulative Boltzmann population level on DP4+ probability was examined. Additionally, the GIAO NMR chemical shift calculation/DP4-type statistical analysis was successfully applied to the determination of the relative configuration of leptolyngbyalide A-C/oscillariolide macrolactone.
BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN
(2022)
Article
Chemistry, Organic
Ryohei Hanzawa, Haruhiko Fuwa
Summary: A collective asymmetric total synthesis of marine tricyclic alkaloids, cylindricines A-H, as well as the proposed structures of cylindricines I and J, was accomplished from a single common spirocyclic pyrrolidine intermediate in a concise manner. A tandem chemoselective oxidation/intramolecular aza-Michael addition/epimerization strategy was utilized to successfully construct the tricyclic skeleton. This work presents a versatile synthetic approach to the cylindricine family of marine tricyclic alkaloids.
Article
Chemistry, Organic
Yoshihiro Goda, Haruhiko Fuwa
Summary: The total synthesis of (-)-enigmazole B was achieved for the first time using a series of efficient chemical reactions, including olefin cross-metathesis, hemiacetalization/intramolecular oxa-Michael addition sequence, Sonogashira cross-coupling, chemo- and regioselective Au-catalyzed intramolecular alkyne hydroalkoxylation, and Yamaguchi macrolactonization.
Article
Chemistry, Organic
Riko Minami, Tsubasa Kasai, Keisuke Murata, Haruhiko Fuwa
Summary: In this study, a convergent total synthesis of (+)-muricatetrocin B, a tetrahydrofuran-containing acetogenin with potent and selective cytotoxicity against HT-29 human colon adenocarcinoma cell line, was achieved in 13 steps. The synthesis is highlighted by a late-stage sequential olefin cross-metathesis/Hartung-Mukaiyama cyclization for the assembly of the 2,5-trans-substituted tetrahydrofuran ring.
Article
Chemistry, Organic
Haruhiko Fuwa
Summary: In this paper, the development of a new strategy for streamlined synthesis of tetrahydropyran-embedded macrolactones is summarized, as well as its successful implementation in the total synthesis of two natural products. The method enables a reduction in steps and an improvement in synthesis efficiency.
Article
Chemistry, Multidisciplinary
Hayato Nakagawa, Haruhiko Fuwa
Summary: Stereodivergent synthesis of 2,5-disubstituted pyrrolidines was achieved through a Au-catalyzed tandem intramolecular alkyne hydroamination/iminium formation/Et3SiH reduction. The stereochemical outcome could be switched by selecting an appropriate nitrogen protecting group. Total synthesis of a diastereomeric pair of alkaloid natural products, monomorine I and indolizidine 195B, was successfully accomplished to demonstrate the synthetic utility of the tandem reaction.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Sandra Raposo-Garcia, Alejandro Cao, Celia Costas, M. Carmen Louzao, Natalia Vilarino, Carmen Vale, Luis M. Botana
Summary: The expanding microorganisms producing ciguatoxins have raised significant concerns about ciguatera fish poisoning (CF), necessitating the development of a reliable and rapid ciguatoxin detection method to ensure food safety. This study evaluated various cell lines for CTX detection and revealed the limitations of the N2a cell line due to low availability of sodium channels and significant O/V damage. The HEK293 Nav cell line, expressing the alpha 1.6 subunit of sodium channels, proved to be sensitive to ciguatoxin without sensitization with O/V, providing an alternative for sodium channel-targeting compound detection.