ArticleThe Journal of biological chemistry2014
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.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 71 citations in OpenAlex.
- Inactivation of SERCA2 at Cys674 induces skeletal muscle atrophy by activating the TGFβ/Smad-S100a4 axis to promote inflammation.Redox biology · 2026Article
- SERCA2 gatekeeper role in aortic autophagy: targeting the CaActa pharmacologica Sinica · 2026Article
- Caveolin-1 Stabilizes SERCA2 to Counteract Acute Kidney Injury via Suppression of CaAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Role of Reductive Stress in the Pathogenesis of Endocrine-Related Metabolic Diseases and Cancer.International journal of molecular sciences · 2025Review
- Calcium dysregulation disrupts mitochondrial homeostasis by interfering AMPK/Drp1 pathway to aggravate plaque progression and instability.Theranostics · 2025Article
- Early Life Stress Influences Oxidative Stress Enzyme Activities in Liver, Heart, Kidney, Suprarenal Glands, and Pancreas in Male and Female Rat Pups.Antioxidants (Basel, Switzerland) · 2024Article
- Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging.Archives of toxicology · 2023Review
- The Brain at High Altitude: From Molecular Signaling to Cognitive Performance.International journal of molecular sciences · 2023Review
- ABCB5Stem cell research & therapy · 2023Article
- Downhill running induced DNA damage enhances mitochondrial membrane permeability by facilitating ER-mitochondria signaling.Journal of muscle research and cell motility · 2022Article
- The substitution of SERCA2 redox cysteine 674 promotes pulmonary vascular remodeling by activating IRE1Acta pharmaceutica Sinica. B · 2022Article
- Sarco/Endoplasmic Reticulum CaCells · 2022Article
- Role of airway smooth muscle cell phenotypes in airway tone and obstruction in guinea pig asthma model.Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology · 2022Article
- Cross-Talk between Mechanosensitive Ion Channels and Calcium Regulatory Proteins in Cardiovascular Health and Disease.International journal of molecular sciences · 2021Review
- Article
- Review
- Inactivation of CysBritish journal of pharmacology · 2020Article
- Redox RegulationAntioxidants & redox signaling · 2020Review
- Effect of Stem Cells, Ascorbic Acid and SERCA1a Gene Transfected Stem Cells in Experimentally Induced Type I Diabetic Myopathy.International journal of stem cells · 2020Article
- Reactive Oxygen Species: Drivers of Physiological and Pathological Processes.Journal of inflammation research · 2020Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.