دورية أكاديمية
Loss of Orai2-Mediated Capacitative Ca 2+ Entry Is Neuroprotective in Acute Ischemic Stroke.
| العنوان: | Loss of Orai2-Mediated Capacitative Ca 2+ Entry Is Neuroprotective in Acute Ischemic Stroke. |
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| المؤلفون: | Stegner D; From the Institute of Experimental Biomedicine, University Hospital Würzburg and Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Germany (D.S., S.H., M.P., V.K., A.B., B.N.)., Hofmann S; From the Institute of Experimental Biomedicine, University Hospital Würzburg and Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Germany (D.S., S.H., M.P., V.K., A.B., B.N.)., Schuhmann MK; Department of Neurology, University Hospital Würzburg, Germany (M.K.S., P.K., G.S.)., Kraft P; Department of Neurology, University Hospital Würzburg, Germany (M.K.S., P.K., G.S.)., Herrmann AM; Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Germany (A.M.H., C.K., S.G.M.)., Popp S; Division of Molecular Psychiatry, Center of Mental Health, University of Würzburg, Germany (S.P., A.P., K.-P.L.)., Höhn M; Carl-Ludwig-Institute for Physiology, University of Leipzig, Germany (M.H., R.K.)., Popp M; From the Institute of Experimental Biomedicine, University Hospital Würzburg and Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Germany (D.S., S.H., M.P., V.K., A.B., B.N.)., Klaus V; From the Institute of Experimental Biomedicine, University Hospital Würzburg and Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Germany (D.S., S.H., M.P., V.K., A.B., B.N.)., Post A; Division of Molecular Psychiatry, Center of Mental Health, University of Würzburg, Germany (S.P., A.P., K.-P.L.)., Kleinschnitz C; Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Germany (A.M.H., C.K., S.G.M.).; Department of Neurology, University Hospital Essen, Germany (C.K.)., Braun A; From the Institute of Experimental Biomedicine, University Hospital Würzburg and Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Germany (D.S., S.H., M.P., V.K., A.B., B.N.)., Meuth SG; Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Germany (A.M.H., C.K., S.G.M.)., Lesch KP; Division of Molecular Psychiatry, Center of Mental Health, University of Würzburg, Germany (S.P., A.P., K.-P.L.).; Laboratory of Psychiatric Neurobiology, Institute of Molecular Medicine, I.M. Sechenov First Moscow State Medical University, Russia (K.-P.L.).; Department of Neuroscience, School for Mental Health and Neuroscience (MHeNS), Maastricht University, the Netherlands (K.-P.L.)., Stoll G; Department of Neurology, University Hospital Würzburg, Germany (M.K.S., P.K., G.S.)., Kraft R; Carl-Ludwig-Institute for Physiology, University of Leipzig, Germany (M.H., R.K.)., Nieswandt B; From the Institute of Experimental Biomedicine, University Hospital Würzburg and Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Germany (D.S., S.H., M.P., V.K., A.B., B.N.). |
| المصدر: | Stroke [Stroke] 2019 Nov; Vol. 50 (11), pp. 3238-3245. Date of Electronic Publication: 2019 Sep 25. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 0235266 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1524-4628 (Electronic) Linking ISSN: 00392499 NLM ISO Abbreviation: Stroke Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 1998- : Baltimore, Md. : Lippincott Williams & Wilkins Original Publication: Dallas : American Heart Association |
| مواضيع طبية MeSH: | Brain Ischemia*/genetics , Brain Ischemia*/metabolism , Brain Ischemia*/pathology , Brain Ischemia*/prevention & control , Calcium Signaling* , Neuroprotection* , Stroke*/genetics , Stroke*/metabolism , Stroke*/pathology , Stroke*/prevention & control, Calcium/*metabolism , ORAI2 Protein/*deficiency, Acute Disease ; Animals ; Cell Death ; Mice ; Mice, Knockout ; Neurons/metabolism ; Neurons/pathology ; ORAI2 Protein/metabolism |
| مستخلص: | Background and Purpose- Ischemic stroke is one of the leading causes of disability and death. The principal goal of acute stroke treatment is the recanalization of the occluded cerebral arteries, which is, however, only effective in a very narrow time window. Therefore, neuroprotective treatments that can be combined with recanalization strategies are needed. Calcium overload is one of the major triggers of neuronal cell death. We have previously shown that capacitative Ca 2+ entry, which is triggered by the depletion of intracellular calcium stores, contributes to ischemia-induced calcium influx in neurons, but the responsible Ca 2+ channel is not known. Methods- Here, we have generated mice lacking the calcium channel subunit Orai2 and analyzed them in experimental stroke. Results- Orai2-deficient mice were protected from ischemic neuronal death both during acute ischemia under vessel occlusion and during ischemia/reperfusion upon successful recanalization. Calcium signals induced by calcium store depletion or oxygen/glucose deprivation were significantly diminished in Orai2-deficient neurons demonstrating that Orai2 is a central mediator of neuronal capacitative Ca 2+ entry and is involved in calcium overload during ischemia. Conclusions- Our experimental data identify Orai2 as an attractive target for pharmaceutical intervention in acute stroke. |
| فهرسة مساهمة: | Keywords: calcium; cell death; neurons; neuroprotection; reperfusion |
| المشرفين على المادة: | 0 (ORAI2 Protein) 0 (Orai2 protein, mouse) SY7Q814VUP (Calcium) |
| تواريخ الأحداث: | Date Created: 20190926 Date Completed: 20200331 Latest Revision: 20200331 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1161/STROKEAHA.119.025357 |
| PMID: | 31551038 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1524-4628 |
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| DOI: | 10.1161/STROKEAHA.119.025357 |