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

Basic Research in Cardiology
Suzanna J LoganWilliam M Chilian

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). N...Continue Reading

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Citations

May 12, 2017·PloS One·Sebastian V RojasAndreas Martens
Feb 16, 2018·Oxidative Medicine and Cellular Longevity·Laurence VernisMeng-Er Huang
Feb 17, 2019·Bioorganic & Medicinal Chemistry Letters·Werner J GeldenhuysAaron R Robart
Sep 8, 2017·ACS Chemical Neuroscience·Werner J GeldenhuysJason R Richardson
Aug 4, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Rachel NechushtaiRon Mittler

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