ArticleAmerican journal of respiratory cell and molecular biology2015
Sarcoendoplasmic reticulum Ca(2+) ATPase. A critical target in chlorine inhalation-induced cardiotoxicity.
Article in American journal of respiratory cell and molecular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 43 citations in OpenAlex.
- A longitudinal characterization of cardiopulmonary and systemic injury following acute chlorine inhalation in rats.Toxicology and applied pharmacology · 2026Article
- A human airway-on-a-chip microphysiological system for modeling chlorine gas toxicity.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Myocardial SERCA2 Protects Against Cardiac Damage and Dysfunction Caused by Inhaled Bromine.The Journal of pharmacology and experimental therapeutics · 2024Article
- Recapitulation of human pathophysiology and identification of forensic biomarkers in a translational model of chlorine inhalation injury.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Epigenetic mechanisms of alveolar macrophage activation in chemical-induced acute lung injury.Frontiers in immunology · 2024Review
- Influence of Chlorinating Agents on the Formation of Stable Biomarkers in Hair for the Retrospective Verification of Exposure.Analytical chemistry · 2022Article
- Safety and toxicology assessment of sodium nitrite administered by intramuscular injection.Toxicology and applied pharmacology · 2021Article
- Sex differences in cardiopulmonary effects of acute bromine exposure.Toxicology research · 2021Article
- Halogen-Induced Chemical Injury to the Mammalian Cardiopulmonary Systems.Physiology (Bethesda, Md.) · 2021Review
- Halogen gas exposure: toxic effects on the parturient.Toxicology mechanisms and methods · 2021Article
- Toxic effects of chlorine gas and potential treatments: a literature review.Toxicology mechanisms and methods · 2021Review
- Chronic cardiac structural damage, diastolic and systolic dysfunction following acute myocardial injury due to bromine exposure in rats.Archives of toxicology · 2021Article
- Erratum: Sarcoendoplasmic Reticulum CaAmerican journal of respiratory cell and molecular biology · 2021Article
- Transient receptor potential channels in pulmonary chemical injuries and as countermeasure targets.Annals of the New York Academy of Sciences · 2020Article
- Circulating and tissue biomarkers as predictors of bromine gas inhalation.Annals of the New York Academy of Sciences · 2020Article
- The effect of cysteine oxidation on DJ-1 cytoprotective function in human alveolar type II cells.Cell death & disease · 2019Article
- Bromine inhalation mimics ischemia-reperfusion cardiomyocyte injury and calpain activation in rats.American journal of physiology. Heart and circulatory physiology · 2019Article
- Hydrogen sulphide increases pulmonary veins and atrial arrhythmogenesis with activation of protein kinase C.Journal of cellular and molecular medicine · 2018Article
- Halogen Inhalation-Induced Lung Injury and Acute Respiratory Distress Syndrome.Chinese medical journal · 2018Review
- Cardiotoxic effects of the novel approved anti-ErbB2 agents and reverse cardioprotective effects of ranolazine.OncoTargets and therapy · 2018Article
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
Autopsy specimens from human victims or experimental animals that die due to acute chlorine gas exposure present features of cardiovascular pathology. We demonstrate acute chlorine inhalation-induced reduction in heart rate and oxygen saturation in rats. Chlorine inhalation elevated chlorine reactants, such as chlorotyrosine and chloramine, in blood plasma. Using heart tissue and primary cardiomyocytes, we demonstrated that acute high-concentration chlorine exposure in vivo (500 ppm for 30 min) caused decreased total ATP content and loss of sarcoendoplasmic reticulum calcium ATPase (SERCA) activity. Loss of SERCA activity was attributed to chlorination of tyrosine residues and oxidation of an important cysteine residue, cysteine-674, in SERCA, as demonstrated by immunoblots and mass spectrometry. Using cardiomyocytes, we found that chlorine-induced cell death and damage to SERCA could be decreased by thiocyanate, an important biological antioxidant, and by genetic SERCA2 overexpression. We also investigated a U.S. Food and Drug Administration-approved drug, ranolazine, used in treatment of cardiac diseases, and previously shown to stabilize SERCA in animal models of ischemia-reperfusion. Pretreatment with ranolazine or istaroxime, another SERCA activator, prevented chlorine-induced cardiomyocyte death. Further investigation of responsible mechanisms showed that ranolazine- and istaroxime-treated cells preserved mitochondrial membrane potential and ATP after chlorine exposure. Thus, these studies demonstrate a novel critical target for chlorine in the heart and identify potentially useful therapies to mitigate toxicity of acute chlorine exposure.
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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.