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Published in: Basic Research in Cardiology 2/2015

01-03-2015 | Original Contribution

Novel thiazolidinedione mitoNEET ligand-1 acutely improves cardiac stem cell survival under oxidative stress

Authors: Suzanna J. Logan, Liya Yin, Werner J. Geldenhuys, Molly K. Enrick, Kelly M. Stevanov, Richard T. Carroll, Vahagn A. Ohanyan, Christopher L. Kolz, William M. Chilian

Published in: Basic Research in Cardiology | Issue 2/2015

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Abstract

Ischemic heart disease (IHD) is a leading cause of death worldwide, and regenerative therapies through exogenous stem cell delivery hold promising potential. One limitation of such therapies is the vulnerability of stem cells to the oxidative environment associated with IHD. Accordingly, manipulation of stem cell mitochondrial metabolism may be an effective strategy to improve survival of stem cells under oxidative stress. MitoNEET is a redox-sensitive, mitochondrial target of thiazolidinediones (TZDs), and influences cellular oxidative capacity. Pharmacological targeting of mitoNEET with the novel TZD, mitoNEET Ligand-1 (NL-1), improved cardiac stem cell (CSC) survival compared to vehicle (0.1 % DMSO) during in vitro oxidative stress (H2O2). 10 μM NL-1 also reduced CSC maximal oxygen consumption rate (OCR) compared to vehicle. Following treatment with dexamethasone, CSC maximal OCR increased compared to baseline, but NL-1 prevented this effect. Smooth muscle α-actin expression increased significantly in CSC following differentiation compared to baseline, irrespective of NL-1 treatment. When CSCs were treated with glucose oxidase for 7 days, NL-1 significantly improved cell survival compared to vehicle (trypan blue exclusion). NL-1 treatment of cells isolated from mitoNEET knockout mice did not increase CSC survival with H2O2 treatment. Following intramyocardial injection of CSCs into Zucker obese fatty rats, NL-1 significantly improved CSC survival after 24 h, but not after 10 days. These data suggest that pharmacological targeting of mitoNEET with TZDs may acutely protect stem cells following transplantation into an oxidative environment. Continued treatment or manipulation of mitochondrial metabolism may be necessary to produce long-term benefits related to stem cell therapies.
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Metadata
Title
Novel thiazolidinedione mitoNEET ligand-1 acutely improves cardiac stem cell survival under oxidative stress
Authors
Suzanna J. Logan
Liya Yin
Werner J. Geldenhuys
Molly K. Enrick
Kelly M. Stevanov
Richard T. Carroll
Vahagn A. Ohanyan
Christopher L. Kolz
William M. Chilian
Publication date
01-03-2015
Publisher
Springer Berlin Heidelberg
Published in
Basic Research in Cardiology / Issue 2/2015
Print ISSN: 0300-8428
Electronic ISSN: 1435-1803
DOI
https://doi.org/10.1007/s00395-015-0471-z

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