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

Title

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

Creator

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

Publisher

Basic research in cardiology

Date

2015
2015-03

Description

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 muM 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 alpha-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.

Subject

Animals; Cardiac/cytology/*drug effects; Cell Differentiation/drug effects; Flow Cytometry; Knockout; Male; Mice; Mitochondrial Membranes/metabolism; Mitochondrial Proteins/metabolism; Myocytes; Oxidative Stress/drug effects/*physiology; Rats; Real-Time Polymerase Chain Reaction; Stem Cells/cytology/*drug effects; Thiazolidinediones/*pharmacology; Zucker

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

19–19

Issue

2

Volume

110

Citation

Logan Suzanna J; Yin Liya; Geldenhuys Werner J; Enrick Molly K; Stevanov Kelly M; Carroll Richard T; Ohanyan Vahagn A; Kolz Christopher L; Chilian William M, “Novel thiazolidinedione mitoNEET ligand-1 acutely improves cardiac stem cell survival under oxidative stress.,” NEOMED Bibliography Database, accessed September 25, 2021, https://neomed.omeka.net/items/show/3177.

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