دورية أكاديمية
Glutathione adducts on sarcoplasmic/endoplasmic reticulum Ca2+ ATPase Cys-674 regulate endothelial cell calcium stores and angiogenic function as well as promote ischemic blood flow recovery.
| العنوان: | Glutathione adducts on sarcoplasmic/endoplasmic reticulum Ca2+ ATPase Cys-674 regulate endothelial cell calcium stores and angiogenic function as well as promote ischemic blood flow recovery. |
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| المؤلفون: | Thompson, Melissa D, Mei, Yu, Weisbrod, Robert M, Silver, Marcy, Shukla, Praphulla C, Bolotina, Victoria M, Cohen, Richard A, Tong, Xiaoyong |
| المصدر: | J Biol Chem ; ISSN:1083-351X ; Volume:289 ; Issue:29 |
| بيانات النشر: | Elsevier Science |
| سنة النشر: | 2014 |
| المجموعة: | PubMed Central (PMC) |
| مصطلحات موضوعية: | Angiogenesis, Calcium, Calcium ATPase, Endothelial Cell, Hypoxia |
| الوصف: | The sarco/endoplasmic reticulum Ca(2+) ATPase (SERCA) is key to Ca(2+) homeostasis and is redox-regulated by reversible glutathione (GSH) adducts on the cysteine (C) 674 thiol that stimulate Ca(2+) uptake activity and endothelial cell angiogenic responses in vitro. We found that mouse hind limb muscle ischemia induced S-glutathione adducts on SERCA in both whole muscle tissue and endothelial cells. To determine the role of S-glutathiolation, we used a SERCA 2 C674S heterozygote knock-in (SKI) mouse lacking half the key thiol. Following hind limb ischemia, SKI animals had decreased SERCA S-glutathione adducts and impaired blood flow recovery. We studied SKI microvascular endothelial cells in which total SERCA 2 expression was unchanged. Cultured SKI microvascular endothelial cells showed impaired migration and network formation compared with wild type (WT). Ca(2+) studies showed decreased nitric oxide (·NO)-induced (45)Ca(2+) uptake into the endoplasmic reticulum (ER) of SKI cells, while Fura-2 studies revealed lower Ca(2+) stores and decreased vascular endothelial growth factor (VEGF)- and ·NO-induced Ca(2+) influx. Adenoviral overexpression of calreticulin, an ER Ca(2+) binding protein, increased ionomycin-releasable stores, VEGF-induced Ca(2+) influx and endothelial cell migration. Taken together, these data indicate that the redox-sensitive Cys-674 thiol on SERCA 2 is required for normal endothelial cell Ca(2+) homeostasis and ischemia-induced angiogenic responses, revealing a novel redox control of angiogenesis via Ca(2+) stores. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://doi.org/10.1074/jbc.M114.554451Test; https://pubmed.ncbi.nlm.nih.gov/24920669Test; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4106311Test/ |
| DOI: | 10.1074/jbc.M114.554451 |
| الإتاحة: | https://doi.org/10.1074/jbc.M114.554451Test https://pubmed.ncbi.nlm.nih.gov/24920669Test https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4106311Test/ |
| حقوق: | © 2014 by The American Society for Biochemistry and Molecular Biology, Inc. |
| رقم الانضمام: | edsbas.81BF2F52 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1074/jbc.M114.554451 |
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