{"id":2550,"date":"2022-06-24T10:10:44","date_gmt":"2022-06-24T01:10:44","guid":{"rendered":"http:\/\/misterx95.myds.me\/?p=2550"},"modified":"2022-07-01T10:28:46","modified_gmt":"2022-07-01T01:28:46","slug":"trpv4-inhibition-prevents-paclitaxel-induced-neurotoxicity-in-preclinicalmodels","status":"publish","type":"post","link":"https:\/\/misterx95.myds.me\/wordpress\/?p=2550","title":{"rendered":"Journal Club – 22.06.24"},"content":{"rendered":"\n

TRPV4 inhibition prevents paclitaxel-induced neurotoxicity in preclinicalmodels<\/strong><\/p>\n\n\n\n

Wolfgang Boehmerlea,b,c,\u204e,1, Petra Huehnchena,b,c,1, Sabrina Lin Lin Leeb,d, Christoph Harmsa,b,c,d,1, Matthias Endresa,b,c,d,e,f,1<\/p>\n\n\n\n

Paclitaxel 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 paclitaxelinduced neuropathy and suggest novel preventive strategies<\/p>\n\n\n\n

TRPV4-inhibition-prevents-paclitaxel-induced-neurotoxicity-in-preclinical-T-models<\/a>Download<\/a><\/div>\n\n\n\n

Keywords: Paclitaxel, Neuropathy, Calcium, TRPV4, Inositol-trisphosphate receptor<\/p>\n\n\n\n

Presenter: Hye In Kim<\/p>\n","protected":false},"excerpt":{"rendered":"

TRPV4 inhibition prevents paclitaxel-induced neurotoxicity in preclinicalmodels Wolfgang Boehmerlea,b,c,\u204e,1, Petra Huehnchena,b,c,1, Sabrina Lin Lin Leeb,d, Christoph Harmsa,b,c,d,1, Matthias Endresa,b,c,d,e,f,1 Paclitaxel is a cytotoxic drug which frequently causes sensory peripheral neuropathy in patients. Increasingevidence suggests that altered intracellular calcium (Ca2+) signals play an important role in the pathogenesis ofthis condition. In the present study, we examined […]<\/p>\n","protected":false},"author":13,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}}},"categories":[1],"tags":[],"_links":{"self":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/2550"}],"collection":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/users\/13"}],"replies":[{"embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=2550"}],"version-history":[{"count":5,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/2550\/revisions"}],"predecessor-version":[{"id":2569,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/2550\/revisions\/2569"}],"wp:attachment":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=2550"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=2550"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=2550"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}