ArticlePloS one2017
Increasing creatine kinase activity protects against hypoxia / reoxygenation injury but not against anthracycline toxicity in vitro.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 29 citations in OpenAlex.
- Prenylcysteine Oxidase 1 Deficiency Protects the Cardiac Muscle Cell Line HL-1 Against Ischaemic/Hypoxic Stress.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Hypercontractility and Oxidative Stress Drive Creatine Kinase Dysfunction in Hypertrophic Cardiomyopathy.Circulation · 2025Article
- Gene delivery of AGAT and GAMT boosts creatine levels in creatine transporter deficiency patient fibroblasts.PloS one · 2025Article
- It Is Not Just About Storing Energy: The Multifaceted Role of Creatine Metabolism on Cancer Biology and Immunology.International journal of molecular sciences · 2024Review
- Mitochondrial Creatine Kinase 2 (Ckmt2) as a Plasma-Based Biomarker for Evaluating Reperfusion Injury in Acute Myocardial Infarction.Biomedicines · 2024Article
- Maintaining energy provision in the heart: the creatine kinase system in ischaemia-reperfusion injury and chronic heart failure.Clinical science (London, England : 1979) · 2024Review
- The Impact of Normobaric Hypoxia and Intermittent Hypoxic Training on Cardiac Biomarkers in Endurance Athletes: A Pilot Study.International journal of molecular sciences · 2024Article
- Identification of potential biomarkers for cerebral palsy and the development of prediction models.Experimental biology and medicine (Maywood, N.J.) · 2024Article
- SERCA2 phosphorylation at serine 663 is a key regulator of CaNature communications · 2023Article
- Proteomics as a Tool for the Study of Mitochondrial Proteome, Its Dysfunctionality and Pathological Consequences in Cardiovascular Diseases.International journal of molecular sciences · 2023Review
- An in vitro approach to understand contribution of kidney cells to human urinary extracellular vesicles.Journal of extracellular vesicles · 2023Article
- Serum Cardiac and Skeletal Muscle Marker Changes in Repetitive Breath-hold Diving.Sports medicine - open · 2021Article
- Conceptus metabolomic profiling reveals stage-specific phenotypes leading up to pregnancy recognition in cattle†.Biology of reproduction · 2021Article
- Phosphorylation in Novel Mitochondrial Creatine Kinase Tyrosine Residues Render Cardioprotection against Hypoxia/Reoxygenation Injury.Journal of lipid and atherosclerosis · 2021Article
- Non-invasive investigation of myocardial energetics in cardiac disease usingCardiovascular diagnosis and therapy · 2020Review
- Genetic variants associated with exercise performance in both moderately trained and highly trained individuals.Molecular genetics and genomics : MGG · 2020Article
- Involvement of the phosphoryl transfer network in gill bioenergetic imbalance of pacamã (Lophiosilurus alexandri) subjected to hypoxia: notable participation of creatine kinase.Fish physiology and biochemistry · 2020Article
- Overexpression of mitochondrial creatine kinase preserves cardiac energetics without ameliorating murine chronic heart failure.Basic research in cardiology · 2020Article
- Comprehensive Evaluation of White Matter Damage and Neuron Death and Whole-Transcriptome Analysis of Rats With Chronic Cerebral Hypoperfusion.Frontiers in cellular neuroscience · 2019Article
- The creatine kinase system as a therapeutic target for myocardial ischaemia-reperfusion injury.Biochemical Society transactions · 2018Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The creatine kinase (CK) phosphagen system is fundamental to cellular energy homeostasis. Cardiomyocytes express three CK isoforms, namely the mitochondrial sarcomeric CKMT2 and the cytoplasmic CKM and CKB. We hypothesized that augmenting CK in vitro would preserve cell viability and function and sought to determine efficacy of the various isoforms. The open reading frame of each isoform was cloned into pcDNA3.1, followed by transfection and stable selection in human embryonic kidney cells (HEK293). CKMT2- CKM- and CKB-HEK293 cells had increased protein and total CK activity compared to non-transfected cells. Overexpressing any of the three CK isoforms reduced cell death in response to 18h hypoxia at 1% O2 followed by 2h re-oxygenation as assayed using propidium iodide: by 33% in CKMT2, 47% in CKM and 58% in CKB compared to non-transfected cells (P<0.05). Loading cells with creatine did not modify cell survival. Transient expression of CK isoforms in HL-1 cardiac cells elevated isoenzyme activity, but only CKMT2 over-expression protected against hypoxia (0.1% for 24h) and reoxygenation demonstrating 25% less cell death compared to non-transfected control (P<0.01). The same cells were not protected from doxorubicin toxicity (250nM for 48h), in contrast to the positive control. These findings support increased CK activity as protection against ischaemia-reperfusion injury, in particular, protection via CKMT2 in a cardiac-relevant cell line, which merits further investigation in vivo.
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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.