دورية أكاديمية

The photoreceptor protective cGMP-analog Rp-8-Br-PET-cGMPS interacts with cGMP-interactors PKGI, PDE1, PDE6, and PKAI in the degenerating mouse retina.

التفاصيل البيبلوغرافية
العنوان: The photoreceptor protective cGMP-analog Rp-8-Br-PET-cGMPS interacts with cGMP-interactors PKGI, PDE1, PDE6, and PKAI in the degenerating mouse retina.
المؤلفون: Rasmussen M; Faculty of Medicine, Department of Clinical Sciences Lund, Lund University, Ophthalmology, Lund, Sweden., Tolone A; Insitute for Ophthalmic Research, University of Tübingen, Tübingen, Germany., Paquet-Durand F; Insitute for Ophthalmic Research, University of Tübingen, Tübingen, Germany., Welinder C; Faculty of Medicine, Department of Clinical Sciences Lund, Mass Spectrometry, Lund University, Lund, Sweden., Schwede F; BIOLOG Life Science Institute GmbH & Co. KG, Bremen, Germany., Ekström P; Faculty of Medicine, Department of Clinical Sciences Lund, Lund University, Ophthalmology, Lund, Sweden.
المصدر: The Journal of comparative neurology [J Comp Neurol] 2023 Jun; Vol. 531 (8), pp. 935-951. Date of Electronic Publication: 2023 Mar 29.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Wiley-Liss Country of Publication: United States NLM ID: 0406041 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-9861 (Electronic) Linking ISSN: 00219967 NLM ISO Abbreviation: J Comp Neurol Subsets: MEDLINE
أسماء مطبوعة: Publication: <2003-> : Hoboken, N.J. : Wiley-Liss
Original Publication: Philadelphia Wistar Institute of Anatomy and Biology
مواضيع طبية MeSH: Cyclic GMP*/metabolism , Cyclic GMP*/pharmacology , Retina*/metabolism, Mice ; Animals ; Cyclic GMP-Dependent Protein Kinases/metabolism
مستخلص: The inherited eye disease retinitis pigmentosa (RP) causes the loss of photoreceptors by a still unknown cell death mechanism. During this degeneration, cyclic guanosine-3',5'-monophosphate (cGMP) levels become elevated, leading to over-activation of the cGMP-binding protein cGMP-dependent 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-8-Br-PET-cGMPS. However, cGMP analogs have previously been shown to interact with numerous targets, so to better understand the therapeutic action of Rp-8-Br-PET-cGMPS, it is necessary to elucidate its target-selectivity 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-8-Br-PET-cGMPS interactors from retinas derived from three different murine RP models (i.e., rd1, rd2, and rd10 mice). Our findings revealed that Rp-8-Br-PET-cGMPS bound seven known cGMP-binding proteins, including PKG1β, PDE1β, PDE1c, PDE6α, and PKA1α. Furthermore, an additional 28 proteins were found to be associated with Rp-8-Br-PET-cGMPS. This latter group included MAPK1/3, which is known to connect with cGMP/PKG in other systems. However, in organotypic retinal cultures, Rp-8-Br-PET-cGMPS had no effect on photoreceptor MAPK1/3 expression or activity. To summarize, Rp-8-Br-PET-cGMPS is more target specific compared to regular cGMP.
(© 2023 The Authors. The Journal of Comparative Neurology published by Wiley Periodicals LLC.)
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فهرسة مساهمة: Keywords: Rp-8-Br-PET-cGMPS; analog; degenerating retina; target-specificity
المشرفين على المادة: 0 (8-bromo-beta-phenylethenoguanosine 3',5'-cyclic monophosphate)
H2D2X058MU (Cyclic GMP)
EC 2.7.11.12 (Cyclic GMP-Dependent Protein Kinases)
تواريخ الأحداث: Date Created: 20230329 Date Completed: 20230411 Latest Revision: 20230528
رمز التحديث: 20231215
DOI: 10.1002/cne.25475
PMID: 36989379
قاعدة البيانات: MEDLINE
الوصف
تدمد:1096-9861
DOI:10.1002/cne.25475