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https://www.readbyqxmd.com/read/27895156/sildenafil-prevents-podocyte-injury-via-ppar-%C3%AE-mediated-trpc6-inhibition
#1
Ramon Sonneveld, Joost G Hoenderop, Andrea M Isidori, Carole Henique, Henry B Dijkman, Jo H Berden, Pierre-Louis Tharaux, Johan van der Vlag, Tom Nijenhuis
Transient receptor potential channel C6 (TRPC6) gain-of-function mutations and increased TRPC6 expression in podocytes induce glomerular injury and proteinuria. Sildenafil reduces TRPC6 expression and activity in nonrenal cell types, although the mechanism is unknown. Peroxisome proliferator-activated receptor γ (PPAR-γ) is a downstream target of sildenafil in the cyclic guanosine monophosphate (cGMP)-activated protein kinase G (PKG) axis. PPAR-γ agonists, like pioglitazone, appear antiproteinuric. We hypothesized that sildenafil inhibits TRPC6 expression in podocytes through PPAR-γ-dependent mechanisms, thereby counteracting podocyte injury and proteinuria...
November 28, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27881772/store-operated-calcium-channel-complex-in-postsynaptic-spines-a-new-therapeutic-target-for-alzheimer-s-disease-treatment
#2
Hua Zhang, Suya Sun, Lili Wu, Ekaterina Pchitskaya, Olga Zakharova, Klementina Fon Tacer, Ilya Bezprozvanny
: Mushroom dendritic spine structures are essential for memory storage and the loss of mushroom spines may explain memory defects in aging and Alzheimer's disease (AD). The stability of mushroom spines depends on stromal interaction molecule 2 (STIM2)-mediated neuronal-store-operated Ca(2+) influx (nSOC) pathway, which is compromised in AD mouse models, in aging neurons, and in sporadic AD patients. Here, we demonstrate that the Transient Receptor Potential Canonical 6 (TRPC6) and Orai2 channels form a STIM2-regulated nSOC Ca(2+) channel complex in hippocampal mushroom spines...
November 23, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27879271/vitamin-d3-prevents-calcium-induced-progression-of-early-stage-prostate-tumors-by-counteracting-trpc6-and-calcium-sensing-receptor-upregulation
#3
Sophie Bernichtein, Natascha Pigat, Nicolas Barry Delongchamps, Florence Boutillon, Virginie Verkarre, Philippe Camparo, Edouard Reyes-Gomez, Arnaud Méjean, Stephane Marie Oudard, Eve M Lepicard, Melanie Viltard, Jean-Claude Souberbielle, Gerard Friedlander, Thierry Capiod, Vincent Goffin
Active surveillance has emerged as an alternative to immediate treatment for men with low-risk prostate cancer. Accordingly, identification of environmental factors that faciliate progression to more aggressive stages is critical for disease prevention. Although calcium-enriched diets have been speculated to increase prostate cancer risk, their impact on early-stage tumors remains unexplored. In this study, we addressed this issue with a large interventional animal study. Mouse models of fully penetrant and slowly-evolving prostate tumorigenesis showed that a high calcium diet dramatically accelerated the progression of prostate intraepithelial neoplasia, by promoting cell proliferation, micro-invasion, tissue inflammation and expression of acknowledged prostate cancer markers...
November 22, 2016: Cancer Research
https://www.readbyqxmd.com/read/27874267/human-digital-meissner-corpuscles-display-immunoreactivity-for-the-multifunctional-ion-channels-trpc6-and-trpv4
#4
P Alonso-González, R Cabo, I San José, A Gago, I C Suazo, O García-Suárez, J Cobo, J A Vega
Ion channels are at the basis of the sensory processes including mechanosensing. Some members of the transient receptor (TRP) ion channel superfamily have been proposed as mechanosensors, but their putative role in mechanotransduction is controversial. Among them there are TRP canonical 6 (TRPC6) and TRP vanilloid 4 (TRPV4) ion channels, which are known to cooperate in mechanical hyperalgesia. Here we investigated the occurrence, distribution and possible co-localization of TRPC6 and TRPV4 in human digital Meissner sensory corpuscles using immunohistochemistry and double immunofluorescence (associate with markers for specific corpuscular constituents)...
November 22, 2016: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
https://www.readbyqxmd.com/read/27865925/orai1-and-orai2-mediate-store-operated-calcium-entry-that-regulates-hl60-cell-migration-and-fak-phosphorylation
#5
R Diez-Bello, I Jardin, G M Salido, J A Rosado
Store-operated Ca(2+) entry (SOCE) is a major mechanism for the regulation of intracellular Ca(2+) homeostasis and cellular function. Emerging evidence has revealed that altered expression and function of the molecular determinants of SOCE play a critical role in the development or maintenance of several cancer hallmarks, including enhanced proliferation and migration. Here we show that, in the acute myeloid leukemia cell line HL60, Orai2 is highly expressed at the transcript level, followed by the expression of Orai1...
November 16, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27861908/differences-in-trpc3-and-trpc6-channels-assembly-in-mesenteric-vascular-smooth-muscle-cells-in-essential-hypertension
#6
Inés Álvarez-Miguel, Pilar Cidad, M Teresa Pérez-García, José Ramón López-López
Increased vascular tone in essential hypertension involves a sustained rise in total peripheral resistance. A model has been proposed in which the combination of membrane depolarization and higher L-type Ca(2+) channel activity generates augmented Ca(2+) influx into vascular smooth muscle cells (VSMCs), contraction and vasoconstriction. The search for culprit ion channels responsible of membrane depolarization has provided several candidates, including members of the TRPC family. TRPC3 and TRPC6 are DAG-activated, non-selective cationic channels contributing to stretch- or agonist-induced depolarization...
November 12, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27834303/single-nucleotide-polymorphisms-and-genotypes-of-transient-receptor-potential-ion-channel-and-acetylcholine-receptor-genes-from-isolated-b-lymphocytes-in-myalgic-encephalomyelitis-chronic-fatigue-syndrome-patients
#7
Sonya Marshall-Gradisnik, Samantha Johnston, Anu Chacko, Thao Nguyen, Peter Smith, Donald Staines
OBJECTIVE: The pathomechanism of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is unknown; however, a small subgroup of patients has shown muscarinic antibody positivity and reduced symptom presentation following anti-CD20 intervention. Given the important roles of calcium (Ca(2+)) and acetylcholine (ACh) signalling in B cell activation and potential antibody development, we aimed to identify relevant single nucleotide polymorphisms (SNPs) and genotypes in isolated B cells from CFS/ME patients...
November 10, 2016: Journal of International Medical Research
https://www.readbyqxmd.com/read/27818466/significant-contribution-of-trpc6-channel-mediated-ca-2-influx-to-the-pathogenesis-of-crohn-s-disease-fibrotic-stenosis
#8
Lin Hai Kurahara, Keizo Hiraishi, Miho Sumiyoshi, Mayumi Doi, Yaopeng Hu, Kunihiko Aoyagi, Yuwen Jian, Ryuji Inoue
Intestinal fibrosis is an intractable complication of Crohn's disease (CD), and, when occurring excessively, causes severe intestinal obstruction that often necessitates surgical resection. The fibrosis is characterized by an imbalance in the turnover of extracellular matrix (ECM) components, where intestinal fibroblasts/myofibroblasts play active roles in ECM production, fibrogenesis and tissue remodeling, which eventually leads to the formation of stenotic lesions. There is however a great paucity of knowledge about how intestinal fibrosis initiates and progresses, which hampers the development of effective pharmacotherapies against CD...
2016: Journal of Smooth Muscle Research, Nihon Heikatsukin Gakkai Kikanshi
https://www.readbyqxmd.com/read/27784066/trpv2-channels-contribute-to-stretch-activated-cation-currents-and-myogenic-constriction-in-retinal-arterioles
#9
Mary K McGahon, José A Fernández, Durga P Dash, Jon McKee, David A Simpson, Alex V Zholos, J Graham McGeown, Tim M Curtis
Purpose: Activation of the transient receptor potential channels, TRPC6, TRPM4, and TRPP1 (PKD2), has been shown to contribute to the myogenic constriction of cerebral arteries. In the present study we sought to determine the potential role of various mechanosensitive TRP channels to myogenic signaling in arterioles of the rat retina. Methods: Rat retinal arterioles were isolated for RT-PCR, Fura-2 Ca2+ microfluorimetry, patch-clamp electrophysiology, and pressure myography studies...
October 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27726466/phage-immunoprecipitation-sequencing-of-autoantigens-in-autoimmune-retinopathy
#10
Samaneh Davoudi, Tina Ahmadi, Evangelia Papavasilieou, Ilya Leskov, Lucia Sobrin
PURPOSE: To identify autoantigens in autoimmune retinopathy patients by phage immunoprecipitation sequencing (PhIP-Seq), a new technique for autoantigen discovery. METHODS: PhIP-Seq was used to sequence putative autoantibodies in plasma from 11 patients with autoimmune retinopathy and eight controls. We compared the autoantibodies' molecular weights with those of proteins detected by Western blot. RESULTS: Several autoantigens were found in cases and not detected in the controls...
October 11, 2016: Ocular Immunology and Inflammation
https://www.readbyqxmd.com/read/27659710/emerging-pathways-driving-early-synaptic-pathology-in-alzheimer-s-disease
#11
Clark A Briggs, Shreaya Chakroborty, Grace E Stutzmann
The current state of the AD research field is highly dynamic is some respects, while seemingly stagnant in others. Regarding the former, our current lack of understanding of initiating disease mechanisms, the absence of effective treatment options, and the looming escalation of AD patients is energizing new research directions including a much-needed re-focusing on early pathogenic mechanisms, validating novel targets, and investigating relevant biomarkers, among other exciting new efforts to curb disease progression and foremost, preserve memory function...
September 20, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27630573/20-hydroxyeicosatetraenoic-acid-20-hete-modulates-canonical-transient-receptor-potential-6-trpc6-channels-in-podocytes
#12
Hila Roshanravan, Eun Y Kim, Stuart E Dryer
The arachidonic acid metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) regulates renal function, including changes in glomerular function evoked during tubuloglomerular feedback (TGF). This study describes the cellular actions of 20-HETE on cultured podocytes, assessed by whole-cell recordings from cultured podocytes combined with pharmacological and cell-biological manipulations of cells. Bath superfusion of 20-HETE activates cationic currents that are blocked by the pan-TRP blocker SKF-96365 and by 50 μM La(3+), and which are attenuated after siRNA knockdown of TRPC6 subunits...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27617218/identification-of-trpcs-genetic-variants-that-modify-risk-for-lung-cancer-based-on-the-pathway-and-two-stage-study
#13
Zili Zhang, Jian Wang, Jianxing He, Xiansheng Zeng, Xindong Chen, Mingmei Xiong, Qipeng Zhou, Meihua Guo, Defu Li, Wenju Lu
OBJECTIVE: Store operated calcium channels (SOCCs) and Receptor-operated calcium channels (ROCCs) are important pathways participating in regulation of intracellular Ca(2 +) concentration in various cell types. The purpose of our study is to determine whether genetic variations in key components of SOCCs and ROCCs are associated with lung cancer risk. METHODS: We identified 236 tagSNPs in 9 key genes related to SOCCs and ROCCs (TRPC1, TRPC3, TRPC4, TRPC6, TRPC7, ORAI1, ORAI2, STIM1, and STIM2) and evaluated their association with lung cancer risk in a two-stage case-control study with a total of 2433 lung cancer cases and 2433 cancer-free controls using Illumina high throughput genotyping platform...
September 2016: Meta Gene
https://www.readbyqxmd.com/read/27614169/endoglin-selectively-modulates-transient-receptor-potential-channel-expression-in-left-and-right-heart-failure
#14
Kevin J Morine, Vikram Paruchuri, Xiaoying Qiao, Mark Aronovitz, Gordon S Huggins, David DeNofrio, Michael S Kiernan, Richard H Karas, Navin K Kapur
INTRODUCTION: Transient receptor potential (TRP) channels are broadly expressed cation channels that mediate diverse physiological stimuli and include canonical (TRPC), melastatin (TRPM), and vanilloid (TRPV) subtypes. Recent studies have implicated a role for TRPC6 channels as an important component of signaling via the cytokine, transforming growth factor beta 1 (TGFβ1) in right (RV) or left ventricular (LV) failure. Endoglin (Eng) is a transmembrane glycoprotein that promotes TRPC6 expression and TGFβ1 activity...
August 21, 2016: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
https://www.readbyqxmd.com/read/27573339/novel-nphs2-variant-in-patients-with-familial-steroid-resistant-nephrotic-syndrome-with-early-onset-slow-progression-and-dominant-inheritance-pattern
#15
Maija Suvanto, Jaakko Patrakka, Timo Jahnukainen, Pia-Maria Sjöström, Matti Nuutinen, Pekka Arikoski, Janne Kataja, Marjo Kestilä, Hannu Jalanko
BACKGROUND: Steroid-resistant nephrotic syndrome (SRNS) is a common cause of end-stage renal disease in children but also occurs as an adult-onset condition. In a subset of SRNS patients, pathogenic variants are found in genes coding for podocyte foot process proteins. The aim of this study was to define the role of pathogenic variants in Finnish patients with familial and sporadic SRNS. METHODS: We analyzed SRNS-related genes NPHS1, NPHS2, NEPH1, ACTN4, TRPC6, INF2, WT1, CD2AP, LAMB2, and PLCE1 for disease-causing variants using direct sequencing of exons and intron/exon boundaries in all members of a family with dominant SRNS with early onset and slow progression to end-stage renal disease...
August 29, 2016: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/27506849/saraf-modulates-trpc1-but-not-trpc6-channel-function-in-a-stim1-independent-manner
#16
Letizia Albarrán, José J López, Luis J Gómez, Ginés M Salido, Juan A Rosado
Canonical transient receptor potential-1 (TRPC1) is an almost ubiquitously expressed channel that plays a relevant role in cell function. As other TRPC members, TRPC1 forms receptor-operated cation channels that exhibit both STIM1-dependent and store-independent behaviour. The STIM1 inhibitor SARAF (for store-operated Ca(2+) entry (SOCE)-associated regulatory factor) modulates SOCE by interaction with the STIM1 region responsible for Orai1 activation (SOAR). Furthermore, SARAF modulates Ca(2+) entry through the arachidonate-regulated Ca(2+) (ARC) channels, consisting of Orai1 and Orai3 heteropentamers and plasma membrane-resident STIM1...
October 15, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27506543/tadalafil-treatment-delays-the-onset-of-cardiomyopathy-in-dystrophin-deficient-hearts
#17
David W Hammers, Margaret M Sleeper, Sean C Forbes, Ai Shima, Glenn A Walter, H Lee Sweeney
BACKGROUND: Cardiomyopathy is a leading cause of mortality among Duchenne muscular dystrophy patients and lacks effective therapies. Phosphodiesterase type 5 is implicated in dystrophic pathology, and the phosphodiesterase type 5 inhibitor tadalafil has recently been studied in a clinical trial for Duchenne muscular dystrophy. METHODS AND RESULTS: Tadalafil was evaluated for the prevention of cardiomyopathy in the mdx mouse and golden retriever muscular dystrophy dog models of Duchenne muscular dystrophy...
2016: Journal of the American Heart Association
https://www.readbyqxmd.com/read/27501229/genomic-alteration-in-head-and-neck-squamous-cell-carcinoma-hnscc-cell-lines-inferred-from-karyotyping-molecular-cytogenetics-and-array-comparative-genomic-hybridization
#18
Worapong Singchat, Ekarat Hitakomate, Budsaba Rerkarmnuaychoke, Aorarat Suntronpong, Beiyuan Fu, Winai Bodhisuwan, Surin Peyachoknagul, Fengtang Yang, Sittichai Koontongkaew, Kornsorn Srikulnath
Genomic alteration in head and neck squamous cell carcinoma (HNSCC) was studied in two cell line pairs (HN30-HN31 and HN4-HN12) using conventional C-banding, multiplex fluorescence in situ hybridization (M-FISH), and array comparative genomic hybridization (array CGH). HN30 and HN4 were derived from primary lesions in the pharynx and base of tongue, respectively, and HN31 and HN12 were derived from lymph-node metastatic lesions belonging to the same patients. Gain of chromosome 1, 7, and 11 were shared in almost all cell lines...
2016: PloS One
https://www.readbyqxmd.com/read/27445840/large-conductance-calcium-activated-potassium-channels-in-glomerulus-from-cell-signal-integration-to-disease
#19
REVIEW
Jie Tao, Zhen Lan, Yunman Wang, Hongya Hei, Lulu Tian, Wanma Pan, Xuemei Zhang, Wen Peng
Large-conductance calcium-activated potassium (BK) channels are currently considered as vital players in a variety of renal physiological processes. In podocytes, BK channels become active in response to stimuli that increase local cytosolic Ca(2+), possibly secondary to activation of slit diaphragm TRPC6 channels by chemical or mechanical stimuli. Insulin increases filtration barrier permeability through mobilization of BK channels. In mesangial cells, BK channels co-expressed with β1 subunits act as a major component of the counteractive response to contraction in order to regulate glomerular filtration...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27430926/-bone-morphogenetic-protein-4-increases-canonical-transient-receptor-potential-protein-expression-by-activating-bone-morphogenetic-protein-receptor-%C3%A2-smad-signaling-pathways-in-pulmonary-arterial-smooth-muscle-cells
#20
X Y Li, P X Ran, J Wang
OBJECTIVE: To observe the effect of bone morphogenetic protein 4 (BMP4) on the Smad signaling pathway in rat distal pulmonary artery smooth muscle cells (PASMCs), and to explore the role of the transient receptor potential ion channel (TRPC) protein 1 and 6(TRPC1, 6) in rat distal PASMCs. METHODS: Distal pulmonary arteries were isolated from adult male Wistar rats(n=6, 280-300 g). The endothelium-denuded pulmonary artery tissue was digested using Collagenase and PASMCs were cultured...
July 2016: Chinese Journal of Tuberculosis and Respiratory Diseases
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