Increasing creatine kinase activity protects against hypoxia / reoxygenation injury but not against anthracycline toxicity in vitro

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 so...

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Bibliographic Details
Published in:PloS one 2017-08, Vol.12 (8), p.e0182994
Main Authors: Zervou, Sevasti, Whittington, Hannah J, Ostrowski, Philip J, Cao, Fang, Tyler, Jack, Lake, Hannah A, Neubauer, Stefan, Lygate, Craig A
Format: Article
Language:English
Subjects:
Adenosine
Analysis
Animals
Anthracycline
Anthracyclines
Anthracyclines - toxicity
Apoptosis
Base Sequence
Biocompatibility
Biology and Life Sciences
Cardiomyocytes
Cell death
Cell Death - drug effects
Cell Hypoxia - drug effects
Cell survival
Cloning, Molecular
Creatine
Creatine kinase
Creatine Kinase - metabolism
Cytoprotection - drug effects
Doxorubicin
Doxorubicin - pharmacology
Drug therapy
Energy balance
Genetics
Health aspects
Heart
Heart cells
Heart diseases
Heart failure
HEK293 Cells
Homeostasis
Humans
Hypoxia
In vitro methods and tests
In vivo methods and tests
Iodides
Ischemia
Isoenzymes - metabolism
Isoforms
Kinases
Medicine
Medicine and Health Sciences
Mice
Mitochondria
Mortality
Open Reading Frames - genetics
Overexpression
Oxidative stress
Oxygen - toxicity
Oxygenation
Permeability
Physical Sciences
Propidium iodide
Reperfusion
Research and Analysis Methods
Rodents
Studies
Toxicity
Transfection
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Summary: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
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0182994