دورية أكاديمية
أعرض في EDS

Evidence for Paracrine Protective Role of Exogenous αA-Crystallin in Retinal Ganglion Cells.

التفاصيل البيبلوغرافية
العنوان: Evidence for Paracrine Protective Role of Exogenous αA-Crystallin in Retinal Ganglion Cells.
المؤلفون: Nath M; Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI 48105., Sluzala ZB; Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI 48105., Phadte AS; Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI 48105.; Currently in Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, PA 19107., Shan Y; Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI 48105., Myers AM; Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI 48105., Fort PE; Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI 48105 patricef@umich.edu.; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48105.
المصدر: ENeuro [eNeuro] 2022 Mar 04; Vol. 9 (2). Date of Electronic Publication: 2022 Mar 04 (Print Publication: 2022).
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Society for Neuroscience Country of Publication: United States NLM ID: 101647362 Publication Model: Electronic-Print Cited Medium: Internet ISSN: 2373-2822 (Electronic) Linking ISSN: 23732822 NLM ISO Abbreviation: eNeuro Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Washington, DC] : Society for Neuroscience, [2014]-
مواضيع طبية MeSH: Crystallins*/chemistry , Crystallins*/genetics , Crystallins*/metabolism, Molecular Chaperones/metabolism ; Recombinant Proteins/metabolism ; Retinal Ganglion Cells/metabolism
مستخلص: Expression and secretion of neurotrophic factors have long been known as a key mechanism of neuroglial interaction in the central nervous system. In addition, several other intrinsic neuroprotective pathways have been described, including those involving small heat shock proteins such as α-crystallins. While initially considered as a purely intracellular mechanism, both αA-crystallins and αB-crystallins have been recently reported to be secreted by glial cells. While an anti-apoptotic effect of such secreted αA-crystallin has been suggested, its regulation and protective potential remain unclear. We recently identified residue threonine 148 (T148) and its phosphorylation as a critical regulator of αA-crystallin intrinsic neuroprotective function. In the current study, we explored how mutation of this residue affected αA-crystallin chaperone function, secretion, and paracrine protective function using primary glial and neuronal cells. After demonstrating the paracrine protective effect of αA-crystallins secreted by primary Müller glial cells (MGCs), we purified and characterized recombinant αA-crystallin proteins mutated on the T148 regulatory residue. Characterization of the biochemical properties of these mutants revealed an increased chaperone activity of the phosphomimetic T148D mutant. Consistent with this observation, we also show that exogeneous supplementation of the phosphomimetic T148D mutant protein protected primary retinal neurons from metabolic stress despite similar cellular uptake. In contrast, the nonphosphorylatable mutant was completely ineffective. Altogether, our study demonstrates the paracrine role of αA-crystallin in the central nervous system as well as the therapeutic potential of functionally enhanced αA-crystallin recombinant proteins to prevent metabolic-stress induced neurodegeneration.
(Copyright © 2022 Nath et al.)
التعليقات: Erratum in: eNeuro. 2022 Aug 30;9(4):. (PMID: 36041825)
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معلومات مُعتمدة: P30 DK020572 United States DK NIDDK NIH HHS; P30 EY007003 United States EY NEI NIH HHS
فهرسة مساهمة: Keywords: chaperone; metabolic stress; neuroprotection; recombinant proteins; αA-crystallin
المشرفين على المادة: 0 (Crystallins)
0 (Molecular Chaperones)
0 (Recombinant Proteins)
تواريخ الأحداث: Date Created: 20220216 Date Completed: 20220404 Latest Revision: 20220830
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC8906792
DOI: 10.1523/ENEURO.0045-22.2022
PMID: 35168949
قاعدة البيانات: MEDLINE
الوصف
تدمد:2373-2822
DOI:10.1523/ENEURO.0045-22.2022