354 results match your criteria trpc5 channel

Involvement of TRPC5 channels, inwardly rectifying K channels, PLCβ and PIP in vasopressin-mediated excitation of medial central amygdala neurons.

J Physiol 2021 Apr 19. Epub 2021 Apr 19.

Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND58203, USA.

Key Points: Activation of V vasopressin receptors facilitates neuronal excitability in the medial nucleus of central amygdala (CeM) V receptor activation excites about 80% CeM neurons by opening a cationic conductance and about 20% CeM neurons by suppressing an inwardly rectifying K (Kir) channels The cationic conductance activated by V receptors is identified as TRPC5 channels PLCβ-mediated depletion of PIP is involved in V receptor-elicited excitation of CeM neurons Intracellular Ca release and PKC are unnecessary for V receptor-mediated excitation of CeM neurons ABSTRACT: Arginine vasopressin (AVP) serves as a hormone in the periphery to modulate water homeostasis and a neuromodulator in the brain to regulate a diverse range of functions including anxiety, social behaviors, cognitive activities and nociception. The amygdala is an essential brain region involved in modulating defensive and appetitive behaviors, pain, and alcohol use disorders. Whereas activation of V receptors in the medial nucleus of the central amygdala (CeM) increases neuronal excitability, the involved ionic and signaling mechanisms have not been determined. Read More

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TRPC5 in cardiovascular diseases.

Rev Cardiovasc Med 2021 Mar;22(1):127-135

Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, 100020 Beijing, P. R. China.

Cardiovascular diseases (CVD), especially acute myocardial infarction, are the leading cause of death, morbidity and disability across the world, affecting millions of people each year. Atherosclerosis (AS) is the major cause of CVD, and is a chronic inflammation involving different cell types and various molecular mechanisms. Ca dynamics of endothelial cells (ECs) and smooth muscle cells (SMCs) exert a significant influence on many aspects of CVD. Read More

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Odontoblast TRPC5 channels signal cold pain in teeth.

Sci Adv 2021 Mar 26;7(13). Epub 2021 Mar 26.

Department of Anesthesiology, Erlangen University Hospital, Friedrich Alexander University of Erlangen-Nuremberg (FAU), Erlangen, Germany.

Teeth are composed of many tissues, covered by an inflexible and obdurate enamel. Unlike most other tissues, teeth become extremely cold sensitive when inflamed. The mechanisms of this cold sensation are not understood. Read More

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Structural basis for human TRPC5 channel inhibition by two distinct inhibitors.

Elife 2021 Mar 8;10. Epub 2021 Mar 8.

State Key Laboratory of Membrane Biology, College of Future Technology, Institute of Molecular Medicine, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing, China.

TRPC5 channel is a nonselective cation channel that participates in diverse physiological processes. TRPC5 inhibitors show promise in the treatment of anxiety disorder, depression, and kidney disease. However, the binding sites and inhibitory mechanism of TRPC5 inhibitors remain elusive. Read More

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Protective effects of dapagliflozin against oxidative stress-induced cell injury in human proximal tubular cells.

PLoS One 2021 19;16(2):e0247234. Epub 2021 Feb 19.

Centre for Atherothrombosis and Metabolic Disease, Hull York Medical School, University of Hull, Hull, United Kingdom.

Elevated reactive oxygen species (ROS) in type 2 diabetes cause cellular damage in many organs. Recently, the new class of glucose-lowering agents, SGLT-2 inhibitors, have been shown to reduce the risk of developing diabetic complications; however, the mechanisms of such beneficial effect are largely unknown. Here we aimed to investigate the effects of dapagliflozin on cell proliferation and cell death under oxidative stress conditions and explore its underlying mechanisms. Read More

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February 2021

Human TRPC5 structures reveal interaction of a xanthine-based TRPC1/4/5 inhibitor with a conserved lipid binding site.

Commun Biol 2020 Nov 23;3(1):704. Epub 2020 Nov 23.

Discovery and Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, LS2 9JT, UK.

TRPC1/4/5 channels are non-specific cation channels implicated in a wide variety of diseases, and TRPC1/4/5 inhibitors have recently entered clinical trials. However, fundamental and translational studies require a better understanding of TRPC1/4/5 channel regulation by endogenous and exogenous factors. Although several potent and selective TRPC1/4/5 modulators have been reported, the paucity of mechanistic insights into their modes-of-action remains a barrier to the development of new chemical probes and drug candidates. Read More

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November 2020

Discovery of novel modulators targeting human TRPC5: Docking-based virtual screening, molecular dynamics simulation and binding affinity predication.

J Mol Graph Model 2021 01 31;102:107795. Epub 2020 Oct 31.

State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China. Electronic address:

Canonical transient receptor potential channel 5 (TRPC5) plays a key role in the regulation of central nervous system, cardiovascular system, kidney disease, cancer, and could be also involved in liver function, arthritis, diabetes-associated complications and so on. However, evidence of TRPC5 function on cellular or organismic levels is sparse. There is still a need for identifying novel and efficient TRPC5 channel modulators to study TRPC5 function. Read More

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January 2021

Effects of Transient Receptor Potential Cation 5 (TRPC5) Inhibitor, NU6027, on Hippocampal Neuronal Death after Traumatic Brain Injury.

Int J Mol Sci 2020 Nov 4;21(21). Epub 2020 Nov 4.

Department of Physiology, College of Medicine, Hallym University, Chuncheon 24252, Korea.

Traumatic brain injury (TBI) can cause physical, cognitive, social, and behavioral changes that can lead to permanent disability or death. After primary brain injury, translocated free zinc can accumulate in neurons and lead to secondary events such as oxidative stress, inflammation, edema, swelling, and cognitive impairment. Under pathological conditions, such as ischemia and TBI, excessive zinc release, and accumulation occurs in neurons. Read More

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November 2020

TRP Channels and Small GTPases Interplay in the Main Hallmarks of Metastatic Cancer.

Front Pharmacol 2020 29;11:581455. Epub 2020 Sep 29.

Laboratoire de Cell Physiology, Université de Lille, Department of Life Sciences, Univ. Lille, Inserm, U1003-PHYCEL, Lille, France.

Transient Receptor Potential (TRP) cations channels, as key regulators of intracellular calcium homeostasis, play a central role in the essential hallmarks of cancer. Among the multiple pathways in which TRPs may be involved, here we focus our attention on the ones involving small guanosine triphosphatases (GTPases), summarizing the main processes associated with the metastatic cascade, such as migration, invasion and tumor vascularization. In the last decade, several studies have highlighted a bidirectional interplay between TRPs and small GTPases in cancer progression: TRP channels may affect small GTPases activity both Ca-dependent or Ca-independent pathways, and, conversely, some small GTPases may affect TRP channels activity through the regulation of their intracellular trafficking to the plasma membrane or acting directly on channel gating. Read More

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September 2020

[Correlation between transient receptor potential canonical channel with heart and kidney injure of rat model of obstructive sleep apnea hypopnea syndrome].

Zhejiang Da Xue Xue Bao Yi Xue Ban 2020 Aug;49(4):439-446

Department of Hypertension, the First Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, China.

Objective: To investigate the expression of transient receptor potential canonical channels (TRPCs) in the heart and kidney of rat model of obstructive sleep apnea hypopnea syndrome (OSAHS).

Methods: Eighteen male SD rats were randomly assigned to intermittent hypoxia (IH) group (=9 ) and control group (=9). In IH group, rats were placed in a chamber and exposed to intermittent hypoxia for 8h (10AM-6PM) daily. Read More

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The Role of Cold-Sensitive Ion Channels in Peripheral Thermosensation.

Front Cell Neurosci 2020 20;14:262. Epub 2020 Aug 20.

Wolfson Centre for Age-Related Diseases, King's College London, London, United Kingdom.

The detection of ambient cold is critical for mammals, who use this information to avoid tissue damage by cold and to maintain stable body temperature. The transduction of information about the environmental cold is mediated by cold-sensitive ion channels expressed in peripheral sensory nerve endings in the skin. Most transduction mechanisms for detecting temperature changes identified to date depend on transient receptor potential (TRP) ion channels. Read More

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Ascorbate-induced oxidative stress mediates TRP channel activation and cytotoxicity in human etoposide-sensitive and -resistant retinoblastoma cells.

Lab Invest 2021 01 18;101(1):70-88. Epub 2020 Sep 18.

Klinik für Augenheilkunde, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.

There are indications that pharmacological doses of ascorbate (Asc) used as an adjuvant improve the chemotherapeutic management of cancer. This favorable outcome stems from its cytotoxic effects due to prooxidative mechanisms. Since regulation of intracellular Ca levels contributes to the maintenance of cell viability, we hypothesized that one of the effects of Asc includes disrupting regulation of intracellular Ca homeostasis. Read More

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January 2021

Transient Receptor Potential Canonical (TRPC) Channels: Then and Now.

Cells 2020 08 28;9(9). Epub 2020 Aug 28.

The Department of Anatomy, Cell Biology & Physiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

Twenty-five years ago, the first mammalian Transient Receptor Potential Canonical (TRPC) channel was cloned, opening the vast horizon of the TRPC field. Today, we know that there are seven TRPC channels (TRPC1-7). TRPCs exhibit the highest protein sequence similarity to the TRP channels. Read More

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Synthesis and Characterization of a Specific Iodine-125-Labeled TRPC5 Radioligand.

ChemMedChem 2020 Oct 2;15(19):1854-1860. Epub 2020 Sep 2.

Department of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA.

The nonselective Ca -permeable transient receptor potential channel subfamily member 5 (TRPC5) belongs to the transient receptor potential canonical (TRPC) superfamily and is widely expressed in the brain. Compelling evidence reveals that TRPC5 plays crucial roles in depression and other psychiatric disorders. To develop a TRPC5 radioligand, following up on our previous effort, we synthesized the iodine compound TZ66127 and its iodine-125-labeled counterpart [ I]TZ66127. Read More

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October 2020

Identification of Novel TRPC5 Inhibitors by Pharmacophore-Based and Structure-Based Approaches.

Comput Biol Chem 2020 Jun 3;87:107302. Epub 2020 Jun 3.

Key Laboratory of Medicinal Chemistry for Natural Resources, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming, China; State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China. Electronic address:

Canonical transient receptor potential-5 (TRPC5), which belongs to the subfamily of transient receptor potential (TRP) channels, is a non-selective cation channel mainly expressed in the central nervous system and shows more restricted expression in the periphery. TRPC5 plays a crucial role in human physiology and pathology, for instance, anxiety, depression, epilepsy, pain, memory and chronic kidney disease (CKD). However, due to lack of the effective and selective inhibitors, its physiological and pathological mechanism remains so far unknown. Read More

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Tubeimoside I Antagonizes Yoda1-Evoked Piezo1 Channel Activation.

Front Pharmacol 2020 25;11:768. Epub 2020 May 25.

Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China.

Piezo1, a mechanosensitive Ca-permeable non-selective cationic ion channel protein, is involved in a wide range of biological processes and plays crucial roles in vascular development. However, the pharmacology of this protein is in its infancy. Yoda1, the first specific chemical activator of Piezo1 channels, can activate Piezo1 in absence of mechanical stimulation. Read More

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Transient receptor potential canonical 5 channel is involved in the cardiac damage related to obstructive sleep apnea-hypopnea syndrome in rats.

Ann Palliat Med 2020 May 12;9(3):895-902. Epub 2020 May 12.

Department of Hypertension, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China.

Background: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is recognized as an independent risk factor of cardiovascular disease. The release of Ca2+ mediated by transient receptor potential canonical (TRPC) channels participates in the hypoxia-induced pathophysiological changes in the cardiovascular systems in case of OSAHS. This study aimed to investigate which subtypes of TRPCs were involved in OSAHS in a rat model of intermittent hypoxia. Read More

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Isoliquiritigenin Inhibits Atherosclerosis by Blocking TRPC5 Channel Expression.

Cardiovasc Ther 2020 7;2020:1926249. Epub 2020 Apr 7.

Department of Pathophysiology, Binzhou Medical University, 346# Guanhai Road, Yantai, Shandong 264003, China.

Isoliquiritigenin (ISL) is a flavonoid isolated mainly from the licorice plant, a traditional Chinese herb. ISL has shown anticancer, anti-inflammatory, antioxidant, and antidiabetic activities. However, the pharmaceutical effects of ISL on atherosclerosis are seldom explored. Read More

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Transient Receptor Potential Canonical 4 and 5 Channel Antagonist ML204 Depolarized Pacemaker Potentials of Interstitial Cells of Cajal.

J Neurogastroenterol Motil 2020 09;26(4):521-528

Department of Physiology, College of Medicine, Chosun University, Gwangju, Korea.

Background/aims: To investigate an effect of ML204 (an inhibitor of transient receptor potential canonical 4 and 5 [TRPC4/5] channels) on interstitial cells of Cajal (ICCs) and therefore determine whether TRPC4/5 channels act on ICC-generated pacemaker activity.

Methods: We enforced whole cell patch clamp analysis, measurements of the intracellular Ca concentration, and reverse transcription polymerase chain reaction to determine the effect of ML204 (10 μM) or englerin A (a selective activator of TRPC4/5 channeles, 10 μM) and the existence of TRPC4/5 in mouse small intestinal ICC.

Results: Treatment of ICCs with ML204 or englerin A caused the membrane potentials to depolarize. Read More

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September 2020

Transient Receptor Potential Canonical 5-Scramblase Signaling Complex Mediates Neuronal Phosphatidylserine Externalization and Apoptosis.

Cells 2020 02 26;9(3). Epub 2020 Feb 26.

School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, China.

Phospholipid scramblase 1 (PLSCR1), a lipid-binding and Ca-sensitive protein located on plasma membranes, is critically involved in phosphatidylserine (PS) externalization, an important process in cell apoptosis. Transient receptor potential canonical 5 (TRPC5), is a nonselective Ca channel in neurons that interacts with many downstream molecules, participating in diverse physiological functions including temperature or mechanical sensation. The interaction between TRPC5 and PLSCR1 has never been reported. Read More

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February 2020

TRPC1 Regulates the Activity of a Voltage-Dependent Nonselective Cation Current in Hippocampal CA1 Neurons.

Cells 2020 02 18;9(2). Epub 2020 Feb 18.

Pharmakologisches Institut, BPC-Marburg, Fachbereich Medizin, Philipps-Universität Marburg, Karl-von-Frisch-Straße 2, 35043 Marburg, Germany.

The cation channel subunit TRPC1 is strongly expressed in central neurons including neurons in the CA1 region of the hippocampus where it forms complexes with TRPC4 and TRPC5. To investigate the functional role of TRPC1 in these neurons and in channel function, we compared current responses to group I metabotropic glutamate receptor (mGluR I) activation and looked for major differences in dendritic morphology in neurons from and mice. mGluR I stimulation resulted in the activation of a voltage-dependent nonselective cation current in both genotypes. Read More

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February 2020

Endothelial Transient Receptor Potential Channels and Vascular Remodeling: Extracellular Ca Entry for Angiogenesis, Arteriogenesis and Vasculogenesis.

Front Physiol 2019 21;10:1618. Epub 2020 Jan 21.

Laboratory of General Physiology, Department of Biology and Biotechnology "L. Spallanzani", University of Pavia, Pavia, Italy.

Vasculogenesis, angiogenesis and arteriogenesis represent three crucial mechanisms involved in the formation and maintenance of the vascular network in embryonal and post-natal life. It has long been known that endothelial Ca signals are key players in vascular remodeling; indeed, multiple pro-angiogenic factors, including vascular endothelial growth factor, regulate endothelial cell fate through an increase in intracellular Ca concentration. Transient Receptor Potential (TRP) channel consist in a superfamily of non-selective cation channels that are widely expressed within vascular endothelial cells. Read More

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January 2020

Involvement of TRPC4 and 5 Channels in Persistent Firing in Hippocampal CA1 Pyramidal Cells.

Cells 2020 02 5;9(2). Epub 2020 Feb 5.

German Center for Neurodegenerative Diseases (DZNE), 39120 Magdeburg, Germany.

Persistent neural activity has been observed in vivo during working memory tasks, and supports short-term (up to tens of seconds) retention of information. While synaptic and intrinsic cellular mechanisms of persistent firing have been proposed, underlying cellular mechanisms are not yet fully understood. In vitro experiments have shown that individual neurons in the hippocampus and other working memory related areas support persistent firing through intrinsic cellular mechanisms that involve the transient receptor potential canonical (TRPC) channels. Read More

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February 2020

Pituitary Adenylate Cyclase-Activating Polypeptide Excites Proopiomelanocortin Neurons: Implications for the Regulation of Energy Homeostasis.

Neuroendocrinology 2021 7;111(1-2):45-69. Epub 2020 Feb 7.

Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, California, USA,

Objective: We examined whether pituitary adenylate cyclase-activating polypeptide (PACAP) excites proopiomelanocortin (POMC) neurons via PAC1 receptor mediation and transient receptor potential cation (TRPC) channel activation.

Methods: Electrophysiological recordings were done in slices from both intact male and ovariectomized (OVX) female PACAP-Cre mice and eGFP-POMC mice.

Results: In recordings from POMC neurons in eGFP-POMC mice, PACAP induced a robust inward current and increase in conductance in voltage clamp, and a depolarization and increase in firing in current clamp. Read More

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February 2020

Regulation of TRPC5 currents by intracellular ATP: Single channel studies.

J Cell Physiol 2020 10 29;235(10):7056-7066. Epub 2020 Jan 29.

Department of Physiology and Pharmacology, State University of New York, Downstate Health Sciences University, Brooklyn, New York.

TRPC5 channels are nonselective cation channels activated by G-protein-coupled receptors. It was previously found that recombinant TRPC5 currents are inhibited by intracellular ATP, when studied by whole-cell patch-clamp recording. In the present study, we investigated the mechanism of ATP inhibition at the single-channel level using patches from HEK-293 cells transiently transfected with TRPC5 and the M1 muscarinic receptor. Read More

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October 2020

Specific Upregulation of TRPC1 and TRPC5 Channels by Mineralocorticoid Pathway in Adult Rat Ventricular Cardiomyocytes.

Cells 2019 12 23;9(1). Epub 2019 Dec 23.

Inserm, UMR-S 1180, Signalisation et Physiopathologie Cardiovasculaire, Université Paris-Saclay, 92296 Châtenay-Malabry, France.

Whereas cardiac TRPC (transient receptor potential canonical) channels and the associated store-operated Ca entry (SOCE) are abnormally elevated during cardiac hypertrophy and heart failure, the mechanism of this upregulation is not fully elucidated but might be related to the activation of the mineralocorticoid pathway. Using a combination of biochemical, Ca imaging, and electrophysiological techniques, we determined the effect of 24-h aldosterone treatment on the TRPCs/Orai-dependent SOCE in adult rat ventricular cardiomyocytes (ARVMs). The 24-h aldosterone treatment (from 100 nM to 1 µM) enhanced depletion-induced Ca entry in ARVMs, as assessed by a faster reduction of Fura-2 fluorescence decay upon the addition of Mn and increased Fluo-4/AM fluorescence following Ca store depletion. Read More

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December 2019

TRPC Channels in Proteinuric Kidney Diseases.

Cells 2019 12 23;9(1). Epub 2019 Dec 23.

Division of Nephrology, Department of Medicine, Duke University; Durham, NC 27710, USA.

Over a decade ago, mutations in the gene encoding (transient receptor potential cation channel, subfamily C, member 6) were linked to development of familial forms of nephrosis. Since this discovery, TRPC6 has been implicated in the pathophysiology of non-genetic forms of kidney disease including focal segmental glomerulosclerosis (FSGS), diabetic nephropathy, immune-mediated kidney diseases, and renal fibrosis. On the basis of these findings, TRPC6 has become an important target for the development of therapeutic agents to treat diverse kidney diseases. Read More

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December 2019

TRPC5 regulates axonal outgrowth in developing retinal ganglion cells.

Lab Invest 2020 02 16;100(2):297-310. Epub 2019 Dec 16.

Department of Molecular and Cellular Neurobiology, Gunma University Graduate School of Medicine, Maebashi, 371-8511, Japan.

The TRPC5 ion channel is activated upon depletion of intracellular calcium stores, as well as by various stimuli such as nitric oxide (NO), membrane stretch, and cold temperatures. TRPC5 is abundantly expressed in the central nervous system where it has important neuronal functions. In the chick retina, TRPC5 expression was shown to be restricted to amacrine cells (ACs) and Müller glial cells, although its expression was also observed in the ganglion cell layer (GCL) in displaced ACs, as determined by their characteristic cell morphology. Read More

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February 2020

Paracetamol inhibits Ca permeant ion channels and Ca sensitization resulting in relaxation of precontracted airway smooth muscle.

J Pharmacol Sci 2020 Feb 24;142(2):60-68. Epub 2019 Jul 24.

Institute for Medical Biology & Hubei Provincial Key Laboratory for Protection and Application of Special Plants in Wuling Area, College of Life Sciences, South-Central University for Nationalities, Wuhan 430074, China. Electronic address:

The purpose of this study was to screen a bronchodilator from old drugs and elucidate the underlying mechanism. Paracetamol (acetaminophen) is a widely used analgesic and antipyretic drug. It has been reported that it inhibits the generation of prostaglandin and histamine, which play roles in asthma. Read More

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February 2020

TRPC5 channel instability induced by depalmitoylation protects striatal neurons against oxidative stress in Huntington's disease.

Biochim Biophys Acta Mol Cell Res 2020 02 6;1867(2):118620. Epub 2019 Dec 6.

Department of Physiology and Institute of Dermatological Science, Seoul National University College of Medicine, Seoul 03080, South Korea. Electronic address:

Protein S-palmitoylation, the covalent lipid modification of the side chain of Cys residues with the 16‑carbon fatty acid palmitate, is the most common acylation, and it enhances the membrane stability of ion channels. This post-translational modification (PTM) determines a functional mechanism of ion channel life cycle from maturation and membrane trafficking to localization. Especially, neurodevelopment is regulated by balancing the level of synaptic protein palmitoylation/depalmitoylation. Read More

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February 2020