000140030 001__ 140030
000140030 005__ 20240321220730.0
000140030 0247_ $$2doi$$a10.1016/j.expneurol.2018.04.014
000140030 0247_ $$2pmid$$apmid:29715474
000140030 0247_ $$2ISSN$$a0014-4886
000140030 0247_ $$2ISSN$$a1090-2430
000140030 0247_ $$2altmetric$$aaltmetric:40780593
000140030 037__ $$aDZNE-2020-06352
000140030 041__ $$aEnglish
000140030 082__ $$a610
000140030 1001_ $$0P:(DE-HGF)0$$aBoehmerle, Wolfgang$$b0$$eCorresponding author
000140030 245__ $$aTRPV4 inhibition prevents paclitaxel-induced neurotoxicity in preclinical models.
000140030 260__ $$aOrlando, Fla.$$bAcademic Press$$c2018
000140030 264_1 $$2Crossref$$3print$$bElsevier BV$$c2018-08-01
000140030 3367_ $$2DRIVER$$aarticle
000140030 3367_ $$2DataCite$$aOutput Types/Journal article
000140030 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1591099666_4414
000140030 3367_ $$2BibTeX$$aARTICLE
000140030 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000140030 3367_ $$00$$2EndNote$$aJournal Article
000140030 520__ $$aPaclitaxel is a cytotoxic drug which frequently causes sensory peripheral neuropathy in patients. Increasing evidence suggests that altered intracellular calcium (Ca2+) signals play an important role in the pathogenesis of this condition. In the present study, we examined the interplay between Ca2+ release channels in the endoplasmic reticulum (ER) and Ca2+ permeable channels in the plasma membrane in the context of paclitaxel mediated neurotoxicity. We observed that in small to medium size dorsal root ganglia neurons (DRGN) the inositol-trisphosphate receptor (InsP3R) type 1 was often concentrated in the periphery of cells, which is in contrast to homogenous ER distribution. G protein-coupled designer receptors were used to further elucidate phosphoinositide mediated Ca2+ signaling: This approach showed strong InsP3 mediated Ca2+ signals close to the plasma membrane, which can be amplified by Ca2+ entry through TRPV4 channels. In addition, our results support a physical interaction and partial colocalization of InsP3R1 and TRPV4 channels. In the context of paclitaxel-induced neurotoxicity, blocking Ca2+ influx through TRPV4 channels reduced cell death in cultured DRGN. Pretreatment of mice with the pharmacological TRPV4 inhibitor HC067047 prior to paclitaxel injections prevented electrophysiological and behavioral changes associated with paclitaxel-induced neuropathy. In summary, these results underline the relevance of TRPV4 signaling for the pathogenesis of paclitaxel-induced neuropathy and suggest novel preventive strategies.
000140030 536__ $$0G:(DE-HGF)POF3-344$$a344 - Clinical and Health Care Research (POF3-344)$$cPOF3-344$$fPOF III$$x0
000140030 542__ $$2Crossref$$i2018-08-01$$uhttps://www.elsevier.com/tdm/userlicense/1.0/
000140030 588__ $$aDataset connected to CrossRef, PubMed,
000140030 650_7 $$2NLM Chemicals$$aAntineoplastic Agents, Phytogenic
000140030 650_7 $$2NLM Chemicals$$aCalcium Channels
000140030 650_7 $$2NLM Chemicals$$aInositol 1,4,5-Trisphosphate Receptors
000140030 650_7 $$2NLM Chemicals$$aTRPV Cation Channels
000140030 650_7 $$2NLM Chemicals$$aTrpv4 protein, mouse
000140030 650_7 $$2NLM Chemicals$$aTrpv4 protein, rat
000140030 650_7 $$0P88XT4IS4D$$2NLM Chemicals$$aPaclitaxel
000140030 650_2 $$2MeSH$$aAnimals
000140030 650_2 $$2MeSH$$aAntineoplastic Agents, Phytogenic: toxicity
000140030 650_2 $$2MeSH$$aCalcium Channels: drug effects
000140030 650_2 $$2MeSH$$aCalcium Channels: metabolism
000140030 650_2 $$2MeSH$$aCalcium Signaling: drug effects
000140030 650_2 $$2MeSH$$aCell Death: drug effects
000140030 650_2 $$2MeSH$$aCell Membrane: drug effects
000140030 650_2 $$2MeSH$$aCell Membrane: metabolism
000140030 650_2 $$2MeSH$$aEndoplasmic Reticulum: drug effects
000140030 650_2 $$2MeSH$$aEndoplasmic Reticulum: metabolism
000140030 650_2 $$2MeSH$$aGanglia, Spinal: pathology
000140030 650_2 $$2MeSH$$aImmunohistochemistry
000140030 650_2 $$2MeSH$$aInositol 1,4,5-Trisphosphate Receptors: genetics
000140030 650_2 $$2MeSH$$aMice, Inbred C57BL
000140030 650_2 $$2MeSH$$aNeurotoxicity Syndromes: pathology
000140030 650_2 $$2MeSH$$aNeurotoxicity Syndromes: prevention & control
000140030 650_2 $$2MeSH$$aPaclitaxel: toxicity
000140030 650_2 $$2MeSH$$aRats
000140030 650_2 $$2MeSH$$aRats, Wistar
000140030 650_2 $$2MeSH$$aTRPV Cation Channels: antagonists & inhibitors
000140030 650_2 $$2MeSH$$aTransfection
000140030 7001_ $$aHuehnchen, Petra$$b1
000140030 7001_ $$aLee, Sabrina Lin Lin$$b2
000140030 7001_ $$aHarms, Christoph$$b3
000140030 7001_ $$0P:(DE-2719)2811033$$aEndres, Matthias$$b4$$eLast author$$udzne
000140030 77318 $$2Crossref$$3journal-article$$a10.1016/j.expneurol.2018.04.014$$b : Elsevier BV, 2018-08-01$$p64-75$$tExperimental Neurology$$v306$$x0014-4886$$y2018
000140030 773__ $$0PERI:(DE-600)1466932-8$$a10.1016/j.expneurol.2018.04.014$$gVol. 306, p. 64 - 75$$p64-75$$q306<64 - 75$$tExperimental neurology$$v306$$x0014-4886$$y2018
000140030 909CO $$ooai:pub.dzne.de:140030$$pVDB
000140030 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2811033$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b4$$kDZNE
000140030 9131_ $$0G:(DE-HGF)POF3-344$$1G:(DE-HGF)POF3-340$$2G:(DE-HGF)POF3-300$$aDE-HGF$$bForschungsbereich Gesundheit$$lErkrankungen des Nervensystems$$vClinical and Health Care Research$$x0
000140030 9141_ $$y2018
000140030 915__ $$0StatID:(DE-HGF)0420$$2StatID$$aNationallizenz$$d2022-11-10$$wger
000140030 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bEXP NEUROL : 2021$$d2022-11-10
000140030 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2022-11-10
000140030 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2022-11-10
000140030 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search$$d2022-11-10
000140030 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC$$d2022-11-10
000140030 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2022-11-10
000140030 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2022-11-10
000140030 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2022-11-10
000140030 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences$$d2022-11-10
000140030 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bEXP NEUROL : 2021$$d2022-11-10
000140030 9201_ $$0I:(DE-2719)1811005$$kAG Endres$$lCoordinator of Clinical Research$$x0
000140030 980__ $$ajournal
000140030 980__ $$aVDB
000140030 980__ $$aI:(DE-2719)1811005
000140030 980__ $$aUNRESTRICTED