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Malm\u00f6hus l\u00e4n","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010816","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Comparative Neurology"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The inherited eye disease retinitis pigmentosa (RP) causes the loss of photoreceptors by a still unknown cell death mechanism. During this degeneration, cyclic guanosine\u20103\u2032,5\u2032\u2010monophosphate (cGMP) levels become elevated, leading to over\u2010activation of the cGMP\u2010binding protein cGMP\u2010dependent protein kinase (PKG). cGMP analogs selectively modified to have inhibitory actions on PKG have aided in impeding photoreceptor death, and one such cGMP analog is Rp\u20108\u2010Br\u2010PET\u2010cGMPS. However, cGMP analogs have previously been shown to interact with numerous targets, so to better understand the therapeutic action of Rp\u20108\u2010Br\u2010PET\u2010cGMPS, it is necessary to elucidate its target\u2010selectivity and hence what potential cellular mechanism(s) it may affect within the photoreceptors. Here, we, therefore, applied affinity chromatography together with mass spectrometry to isolate and identify Rp\u20108\u2010Br\u2010PET\u2010cGMPS interactors from retinas derived from three different murine RP models (i.e., <jats:italic>rd1, rd2<\/jats:italic>, and <jats:italic>rd10<\/jats:italic> mice). Our findings revealed that Rp\u20108\u2010Br\u2010PET\u2010cGMPS bound seven known cGMP\u2010binding proteins, including PKG1\u03b2, PDE1\u03b2, PDE1c, PDE6\u03b1, and PKA1\u03b1. Furthermore, an additional 28 proteins were found to be associated with Rp\u20108\u2010Br\u2010PET\u2010cGMPS. This latter group included MAPK1\/3, which is known to connect with cGMP\/PKG in other systems. However, in organotypic retinal cultures, Rp\u20108\u2010Br\u2010PET\u2010cGMPS had no effect on photoreceptor MAPK1\/3 expression or activity. To summarize, Rp\u20108\u2010Br\u2010PET\u2010cGMPS is more target specific compared to regular cGMP.<\/jats:p>","DOI":"10.1002\/cne.25475","type":"journal-article","created":{"date-parts":[[2023,3,29]],"date-time":"2023-03-29T18:51:16Z","timestamp":1680115876000},"page":"935-951","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The photoreceptor protective cGMP\u2010analog Rp\u20108\u2010Br\u2010PET\u2010cGMPS interacts with cGMP\u2010interactors PKGI, PDE1, PDE6, and PKAI in the degenerating mouse retina"],"prefix":"10.1002","volume":"531","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4932-8456","authenticated-orcid":false,"given":"Michel","family":"Rasmussen","sequence":"first","affiliation":[{"name":"Faculty of Medicine Department of Clinical Sciences Lund Lund University Ophthalmology  Lund Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arianna","family":"Tolone","sequence":"additional","affiliation":[{"name":"Insitute for Ophthalmic Research University of T\u00fcbingen  T\u00fcbingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francois","family":"Paquet\u2010Durand","sequence":"additional","affiliation":[{"name":"Insitute for Ophthalmic Research University of T\u00fcbingen  T\u00fcbingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9626-0576","authenticated-orcid":false,"given":"Charlotte","family":"Welinder","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Department of Clinical Sciences Lund, Mass Spectrometry Lund University  Lund Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Schwede","sequence":"additional","affiliation":[{"name":"BIOLOG Life Science Institute GmbH &amp; Co. KG  Bremen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Per","family":"Ekstr\u00f6m","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Department of Clinical Sciences Lund Lund University Ophthalmology  Lund Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,3,29]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0112142"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2006.10.031"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/FMICB.2020.602803"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.NEUROBIOLAGING.2014.07.040"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3791\/61868"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19030801"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476\u20105381.1995.tb15112.x"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0891\u20100618(01)00140\u2010"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschembio.7b00369"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.CELLSIG.2008.03.009"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0042\u20106989(01)00146\u20108"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.11.4845"},{"key":"e_1_2_11_14_1","first-page":"1","volume-title":"Advances in experimental medicine and biology","author":"Cote R. 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