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https://www.readbyqxmd.com/read/29752243/mechanical-stimulation-of-the-retina-therapeutic-feasibility-and-cellular-mechanism
#1
Corey M Rountree, Chen Meng, John B Troy, Laxman Saggere
Retinal prostheses that seek to restore vision by artificially stimulating retinal neurons with electrical current are an emerging treatment for photoreceptor degenerative diseases but face difficulties achieving naturalistic vision with high spatial resolution. Here, we report the unexpected discovery of a technique for mechanically stimulating retinal neurons with the potential to bypass the limitations of electrical stimulation. We found that pulsatile injections of standard Ames medium solution into explanted retinas of wild type rats under certain injection conditions (pulse-width > 50ms at 0...
May 2018: IEEE Transactions on Neural Systems and Rehabilitation Engineering
https://www.readbyqxmd.com/read/29746471/atypical-pharmacology-of-schistosome-trpa1-like-ion-channels
#2
Swarna Bais, Corbett T Berry, Xiaohong Liu, Gordon Ruthel, Bruce D Freedman, Robert M Greenberg
Parasitic flatworms of the genus Schistosoma cause schistosomiasis, a neglected tropical disease estimated to affect over 200 million people worldwide. Praziquantel is the only antischistosomal currently available for treatment, and there is an urgent need for new therapeutics. Ion channels play key roles in physiology and are targets for many anthelmintics, yet only a few representatives have been characterized in any detail in schistosomes and other parasitic helminths. The transient receptor potential (TRP) channel superfamily comprises a diverse family of non-selective cation channels that play key roles in sensory transduction and a wide range of other functions...
May 10, 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29740060/osm-9-and-an-amiloride-sensitive-channel-but-not-pkd-2-are-involved-in-mechanosensation-in-c-elegans-male-ray-neurons
#3
Hu Zhang, Xiaomin Yue, Hankui Cheng, Xiaoyan Zhang, Yang Cai, Wenjuan Zou, Guifang Huang, Lufeng Cheng, Fang Ye, Lijun Kang
Mechanotransduction is crucial for touch sensation, hearing, proprioception, and pain sensing. In C. elegans, male ray neurons have been implicated to be involved in the mechanosensation required for mating behavior. However, whether ray neurons directly sense mechanical stimulation is not yet known, and the underlying molecular mechanisms have not been identified. Using in vivo calcium imaging, we recorded the touch-induced calcium responses in male ray neurons. Our data demonstrated that ray neurons are sensitive to mechanical stimulation in a neurotransmitter-independent manner...
May 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29728656/conformational-plasticity-in-the-selectivity-filter-of-the-trpv2-ion-channel
#4
Lejla Zubcevic, Son Le, Huanghe Yang, Seok-Yong Lee
Transient receptor potential vanilloid (TRPV) channels are activated by ligands and heat and are involved in various physiological processes. In contrast to the architecturally related voltage-gated cation channels, TRPV1 and TRPV2 subtypes possess another activation gate at the selectivity filter that can open widely enough to permeate large organic cations. Despite recent structural advances, the mechanism of selectivity filter gating and permeation for both metal ions and large molecules by TRPV1 or TRPV2 is not well known...
May 2018: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/29719445/mechanisms-involved-in-adenosine-pharmacological-preconditioning-induced-cardioprotection
#5
REVIEW
Lovedeep Singh, Ritu Kulshrestha, Nirmal Singh, Amteshwar Singh Jaggi
Adenosine is a naturally occurring breakdown product of adenosine triphosphate and plays an important role in different physiological and pathological conditions. Adenosine also serves as an important trigger in ischemic and remote preconditioning and its release may impart cardioprotection. Exogenous administration of adenosine in the form of adenosine preconditioning may also protect heart from ischemia-reperfusion injury. Endogenous release of adenosine during ischemic/remote preconditioning or exogenous adenosine during pharmacological preconditioning activates adenosine receptors to activate plethora of mechanisms, which either independently or in association with one another may confer cardioprotection during ischemia-reperfusion injury...
May 2018: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/29610016/trpv2-channel-inhibitors-attenuate-fibroblast-differentiation-and-contraction-mediated-by-keratinocyte-derived-tgf-%C3%AE-1-in-an-in-vitro-wound-healing-model-of-rats
#6
Taro Ishii, Kunitoshi Uchida, Shozaburo Hata, Mitsutoki Hatta, Tomo Kita, Yuki Miyake, Kazuhiko Okamura, Sachio Tamaoki, Hiroyuki Ishikawa, Jun Yamazaki
BACKGROUND: Keratinocytes release several factors that are involved in wound contracture and scar formation. We previously reported that a three-dimensional reconstruction model derived from rat skin represents a good wound healing model. OBJECTIVE: We characterized the role of transient receptor potential (TRP) channels in the release of transforming growth factor (TGF)-β1 from keratinocytes and the differentiation of fibroblasts to identify possible promising pharmacological approaches to prevent scar formation and contractures...
March 6, 2018: Journal of Dermatological Science
https://www.readbyqxmd.com/read/29584409/the-structural-basis-of-calcium-dependent-inactivation-of-the-transient-receptor-potential-vanilloid-5-channel
#7
Fedir M Bokhovchuk, Neil Bate, Nadezhda V Kovalevskaya, Benjamin T Goult, Chris A E M Spronk, Geerten W Vuister
The Transient Receptor Potential Vanilloid Channel subfamily member 5 (TRPV5) is a highly selective calcium ion channel predominately expressed in the kidney epithelium that plays an essential role in calcium reabsorption from renal infiltrate. In order to maintain Ca2+ homeostasis, TRPV5 possesses a tightly regulated negative feedback mechanism, where the ubiquitous Ca2+-binding protein Calmodulin (CaM) directly binds to the intracellular TRPV5 C-terminus, thus regulating TRPV5. Here we report on the characterisation of the TRPV5 C-terminal CaM binding site and its interaction with CaM at an atomistic level...
March 27, 2018: Biochemistry
https://www.readbyqxmd.com/read/29574261/the-expression-of-trpv-channels-prostaglandin-e2-and-pro-inflammatory-cytokines-during-behavioural-fever-in-fish
#8
Sebastian Boltana, Nataly Sanhueza, Andrea Donoso, Andrea Aguilar, Diego Crespo, Daniela Vergara, Gabriel Arriagada, Byron Morales-Lange, Luis Mercado, Sonia Rey, Lluis Tort, Simon Mackenzie
A fever, or increased body temperature, is a symptom of inflammation, which is a complex defence reaction of the organism to pathogenic infections. After pathogens enter the body, immune cells secrete a number of agents, the functions of which stimulate the body to develop a functional immune and fever response. In mammals it is known that PGE2 is the principal mediator of fever. The extent to which PGE2 and other pro-inflammatory cytokines such as TNF-α, IL-6, or IL-1β could be involved in the induction of behavioural fever in fish remains to be clarified...
March 21, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29535773/ion-channel-expression-and-characterization-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#9
Zhihan Zhao, Huan Lan, Ibrahim El-Battrawy, Xin Li, Fanis Buljubasic, Katherine Sattler, Gökhan Yücel, Siegfried Lang, Malte Tiburcy, Wolfram-Hubertus Zimmermann, Lukas Cyganek, Jochen Utikal, Thomas Wieland, Martin Borggrefe, Xiao-Bo Zhou, Ibrahim Akin
Background: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are providing new possibilities for the biological study, cell therapies, and drug discovery. However, the ion channel expression and functions as well as regulations in hiPSC-CMs still need to be fully characterized. Methods: Cardiomyocytes were derived from hiPS cells that were generated from two healthy donors. qPCR and patch clamp techniques were used for the study. Results: In addition to the reported ion channels, INa , ICa-L , ICa-T , If , INCX , IK1 , Ito , IKr , IKs IKATP , IK-pH , ISK1-3 , and ISK4 , we detected both the expression and currents of ACh-activated (KACh) and Na+ -activated (KNa) K+ , volume-regulated and calcium-activated (Cl-Ca) Cl- , and TRPV channels...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29518656/copper-induced-activation-of-trp-channels-promotes-extracellular-calcium-entry-and-activation-of-camk-pka-pkc-pkg-and-cblpk-leading-to-increased-expression-of-antioxidant-enzymes-in-ectocarpus-siliculosus
#10
Alberto González, Claudio A Sáez, Bernardo Morales, Alejandra Moenne
The existence of functional Transient Receptor Potential (TRP) channels was analyzed in Ectocarpus siliculosus using agonists of human TRPs and specific antagonists of TRPA1, TRPC5, TRPM8 and TRPV; intracellular calcium was detected for 60 min. Increases in intracellular calcium were observed at 13, 29, 39 and 50-52 min, which appeared to be mediated by the activation of TRPM8/V1 at 13 min, TRPV1 at 29 min, TRPA1/V1 at 39 min and TRPA1/C5 at 50-52 min. In addition, intracellular calcium increases appear to be due to extracellular calcium entry, not requiring protein kinase activation...
May 2018: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/29510166/uterine-adenocarcinoma-in-the-rat-induced-by-afidopyropen-an-analysis-of-the-lesion-s-induction-progression-and-its-relevance-to-humans
#11
Andrew Van Cott, Markus Frericks, Charles Hastings, Naveed Honarvar, Burkhard Flick, Eric Fabian, Bennard van Ravenzwaay
Afidopyropen is a novel insecticide that acts as a TRPV channel modulator in chordotonal organs of target insects. In two carcinogenicity studies with Fischer rats, an increased incidence of uterine adenocarcinomas was observed at 1000 and 3000 ppm. This finding prompted an investigation of the mechanism of the tumor formation as well as the relevance of this mechanism to humans. The mechanistic work took parallel paths: one path investigated the pharmacokinetic properties of the test substance at the doses where the tumors were found; while the second path examined the key mechanistic events that culminated in uterine adenocarcinomas...
June 2018: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/29498086/gossypol-stimulates-opening-of-a-ca-2-and-na-permeable-but-ni-2-and-co-2-impermeable-pore-in-bend-3-endothelial-cells
#12
Cing-Yu Chen, Wen-Chuan Lin, Kar-Lok Wong, Ka-Shun Cheng, Yuk-Man Leung, Shu-Er Yang
Gossypol, a polyphenolic dialdehyde toxin isolated from cotton seed, has anti-cancer properties and has recently shown some success in the treatment of glioma. Its effects on brain neurons and blood vessels are poorly understood. In this work we examined the effects of gossypol on cytosolic Ca2+ concentration ([Ca2+ ]i ) of mouse brain bEND.3 endothelial cells. Cell viability tests revealed that after 3 hour and 18 hour exposures, 10 µmol/L gossypol caused 23% and 65% cell death, respectively; 3 µmol/L gossypol caused no and 21% cell death, respectively...
March 1, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29483651/cryo-em-and-x-ray-structures-of-trpv4-reveal-insight-into-ion-permeation-and-gating-mechanisms
#13
Zengqin Deng, Navid Paknejad, Grigory Maksaev, Monica Sala-Rabanal, Colin G Nichols, Richard K Hite, Peng Yuan
The transient receptor potential (TRP) channel TRPV4 participates in multiple biological processes, and numerous TRPV4 mutations underlie several distinct and devastating diseases. Here we present the cryo-EM structure of Xenopus tropicalis TRPV4 at 3.8-Å resolution. The ion-conduction pore contains an intracellular gate formed by the inner helices, but lacks any extracellular gate in the selectivity filter, as observed in other TRPV channels. Anomalous X-ray diffraction analyses identify a single ion-binding site in the selectivity filter, thus explaining TRPV4 nonselectivity...
March 2018: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/29466323/transplantation-of-recombinant-vascular-endothelial-growth-factor-vegf-189-neural-stem-cells-downregulates-transient-receptor-potential-vanilloid-1-trpv1-and-improves-motor-outcome-in-spinal-cord-injury
#14
Yun Zeng, Heng Han, Bing Tang, Jie Chen, Dan Mao, Min Xiong
BACKGROUND Spinal cord injury (SCI) causes a rapid loss of motor neurons, leading to weakness and paralysis. Transplantation of neural stem cells is known to restore the neuronal activity but is inefficient due to limited regenerative capability and low rate of survival. There has been an emphasis on the use of growth factors along with neural stem cells (NSCs) to enhance the neuronal recovery. Transplantation of recombinant NSCs with vascular endothelial growth factor (VEGF) might promote neuronal repair. This effect might be attributed to the reduced transient receptor potential vanilloid 1 (TRPV1) expression following transplantation...
February 21, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29465314/endogenously-generated-arachidonate-derived-ligands-for-trpv1-induce-cardiac-protection-in-sepsis
#15
Jianmin Chen, Alexander J P Hamers, Michaela Finsterbusch, Gianmichele Massimo, Maleeha Zafar, Roger Corder, Romain A Colas, Jesmond Dalli, Christoph Thiemermann, Amrita Ahluwalia
The severity of cardiac dysfunction predicts mortality in sepsis. Activation of transient receptor potential vanilloid receptor type (TRPV)-1, a predominantly neuronal nonselective cation channel, has been shown to improve outcome in sepsis and endotoxemia. However, the role of TRPV1 and the identity of its endogenous ligands in the cardiac dysfunction caused by sepsis and endotoxemia are unknown. Using TRPV1-/- and TRPV1+/+ mice, we showed that endogenous activation of cardiac TRPV1 during sepsis is key to limiting the ensuing cardiac dysfunction...
February 20, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29464560/transient-receptor-potential-trp-channels
#16
Amrita Samanta, Taylor E T Hughes, Vera Y Moiseenkova-Bell
Transient Receptor Potential (TRP) channels are evolutionarily conserved integral membrane proteins. The mammalian TRP superfamily of ion channels consists of 28 cation permeable channels that are grouped into six subfamilies based on sequence homology (Fig. 6.1). The canonical TRP (TRPC) subfamily is known for containing the founding member of mammalian TRP channels. The vanilloid TRP (TRPV) subfamily has been extensively studied due to the heat sensitivity of its founding member. The melastatin-related TRP (TRPM) subfamily includes some of the few known bi-functional ion channels, which contain functional enzymatic domains...
2018: Sub-cellular Biochemistry
https://www.readbyqxmd.com/read/29452097/stimulation-of-trpv1-channels-activates-the-ap-1-transcription-factor
#17
Tobias M Backes, Oliver G Rössler, Xin Hui, Carsten Grötzinger, Peter Lipp, Gerald Thiel
Transient receptor potential vanilloid 1 (TRPV1) channels were originally described as the receptors of capsaicin, the main constituent of hot chili pepper. The biological functions of TRPV1 channels include pain sensation and inflammatory thermal hyperalgesia. Here, we show that stimulation of HEK293 cells expressing TRPV1 channels (H2C1 cells) with capsaicin or the TRPV1 ligand resiniferatoxin activated transcription mediated by the transcription factor AP-1. No cell death was occurring under these experimental conditions...
April 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29407000/the-arteriolar-injury-in-hypertension
#18
Qian Ru Gu, Yang Yang Li, Guo Rong Chen, M J Quinn
In 1937, Drs. Moritz and Oldt described arteriolar injuries in the kidneys (and other viscera) in hypertension, across the age range, in both sexes, and, in different races. This hypothesis proposes that injuries to vasomotor nerves cause the arteriolar injury in the kidney in hypertension, (as well as that in the uterus in preeclampsia). Different patterns of perivascular hyalinisation in different viscera are clues to the varying causes and consequences of arteriolar injury. In the uterus there is a symmetrical, perivascular "halo of hyalinisation" that marks the lines of extension of regenerating, injured nerves to the placental bed, whereas in the kidney there is a disordered and asymmetrical "halo of hyalinisation" where persistent, and recurrent, increases in intravascular pressures interrupt development of regenerating nerves...
February 2018: Medical Hypotheses
https://www.readbyqxmd.com/read/29373067/role-of-trp-channels-in-dinoflagellate-mechanotransduction
#19
J B Lindström, N T Pierce, M I Latz
Transient receptor potential (TRP) ion channels are common components of mechanosensing pathways, mainly described in mammals and other multicellular organisms. To gain insight into the evolutionary origins of eukaryotic mechanosensory proteins, we investigated the involvement of TRP channels in mechanosensing in a unicellular eukaryotic protist, the dinoflagellate Lingulodinium polyedra. BLASTP analysis of the protein sequences predicted from the L. polyedra transcriptome revealed six sequences with high similarity to human TRPM2, TRPM8, TRPML2, TRPP1, and TRPP2; and characteristic TRP domains were identified in all sequences...
October 2017: Biological Bulletin
https://www.readbyqxmd.com/read/29354996/-analysis-of-specificity-of-shenque-cv-8-based-on-vascular-biology
#20
Jinfeng Jiang, Wangfang Xu, Xinggen Yu, Xiaojing Wu
To analyze the structural specificity of Shenque (CV 8) in terms of vascular biology from the three aspects of structure, tissue and molecular anatomies. On structural anatomy Shenque (CV 8) possessed defined vascular structure and was the only acupoint directly affected vascular intima. The basis of the specific therapeutic effects was owing to its relation with vessel and abundant microcirculation. Endothelial cells and microvascular endothelial cells were the tissue basis of the starting of therapeutic specificity...
December 12, 2017: Zhongguo Zhen Jiu, Chinese Acupuncture & Moxibustion
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