دورية أكاديمية
أعرض في EDS

Presenilin-1 ΔE9 mutation associated sarcoplasmic reticulum leak alters [Ca 2+ ] i distribution in human iPSC-derived cardiomyocytes.

التفاصيل البيبلوغرافية
العنوان: Presenilin-1 ΔE9 mutation associated sarcoplasmic reticulum leak alters [Ca 2+ ] i distribution in human iPSC-derived cardiomyocytes.
المؤلفون: Naumenko N; A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland., Koivumäki JT; BioMediTech, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland., Lunko O; A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland., Tuomainen T; A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland., Leigh R; A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland., Rabiee M; A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland., Laurila J; A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland., Oksanen M; A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland., Lehtonen S; A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland; Neuroscience Center, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland., Koistinaho J; A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland; Neuroscience Center, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland., Tavi P; A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland. Electronic address: pasi.tavi@uef.fi.
المصدر: Journal of molecular and cellular cardiology [J Mol Cell Cardiol] 2024 Aug; Vol. 193, pp. 78-87. Date of Electronic Publication: 2024 Jun 06.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Academic Press Country of Publication: England NLM ID: 0262322 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-8584 (Electronic) Linking ISSN: 00222828 NLM ISO Abbreviation: J Mol Cell Cardiol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London, New York, Academic Press.
مواضيع طبية MeSH: Induced Pluripotent Stem Cells*/metabolism , Myocytes, Cardiac*/metabolism , Presenilin-1*/genetics , Presenilin-1*/metabolism , Sarcoplasmic Reticulum*/metabolism , Calcium*/metabolism , Mutation* , Calcium Signaling* , Ryanodine Receptor Calcium Release Channel*/metabolism , Ryanodine Receptor Calcium Release Channel*/genetics, Humans
مستخلص: Mutations in ubiquitously expressed presenilin genes (PSENs) lead to early-onset familial Alzheimer's disease (FAD), but patients carrying the mutation also suffer from heart diseases. To elucidate the cardiac myocyte specific effects of PSEN ΔE9, we studied cardiomyocytes derived from induced pluripotent stem cells (iPSC-CMs) from patients carrying AD-causing PSEN1 exon 9 deletion (PSEN1 ΔE9). When compared with their isogenic controls, PSEN1 ΔE9 cardiomyocytes showed increased sarcoplasmic reticulum (SR) Ca 2+ leak that was resistant to blockage of ryanodine receptors (RyRs) by tetracaine or inositol-3-reseceptors (IP 3 Rs) by 2-ABP. The SR Ca 2+ leak did not affect electrophysiological properties of the hiPSC-CMs, but according to experiments and in silico simulations the leak induces a diastolic buildup of [Ca 2+ ] near the perinuclear SR and reduces the releasable Ca 2+ during systole. This demonstrates that PSEN1 ΔE9 induced SR Ca 2+ leak has specific effects in iPSC-CMs, reflecting their unique structural and calcium signaling features. The results shed light on the physiological and pathological mechanisms of PSEN1 in cardiac myocytes and explain the intricacies of comorbidity associated with AD-causing mutations in PSEN1.
Competing Interests: Declaration of competing interest None.
(Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
فهرسة مساهمة: Keywords: Alzheimer's disease; EC-coupling; Inherited heart disease; Mathematical modeling
المشرفين على المادة: 0 (Presenilin-1)
SY7Q814VUP (Calcium)
0 (Ryanodine Receptor Calcium Release Channel)
0 (PSEN1 protein, human)
تواريخ الأحداث: Date Created: 20240608 Date Completed: 20240719 Latest Revision: 20240722
رمز التحديث: 20240722
DOI: 10.1016/j.yjmcc.2024.06.003
PMID: 38851626
قاعدة البيانات: MEDLINE
الوصف
تدمد:1095-8584
DOI:10.1016/j.yjmcc.2024.06.003