NecroX-5 protects mitochondrial oxidative phosphorylation capacity and preserves PGC1alpha expression levels during hypoxia/reoxygenation injury.
10.4196/kjpp.2016.20.2.201
- Author:
Vu Thi THU
1
;
Hyoung Kyu KIM
;
Le Thanh LONG
;
Bayalagmaa NYAMAA
;
In Sung SONG
;
To Thanh THUY
;
Nguyen Quang HUY
;
Jubert MARQUEZ
;
Soon Ha KIM
;
Nari KIM
;
Kyung Soo KO
;
Byoung Doo RHEE
;
Jin HAN
Author Information
1. National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan 47392, Korea. phyhanj@inje.ac.kr
- Publication Type:In Vitro ; Original Article
- Keywords:
Hypoxia;
Mitochondria;
NecroX;
Oxidative phosphorylation;
PCG1alpha
- MeSH:
Animals;
Anoxia;
Blotting, Western;
Citric Acid;
Electron Transport;
Heart;
Mitochondria;
Oxidative Phosphorylation*;
Peroxisomes;
Rats;
Real-Time Polymerase Chain Reaction;
Spectrum Analysis
- From:The Korean Journal of Physiology and Pharmacology
2016;20(2):201-211
- CountryRepublic of Korea
- Language:English
-
Abstract:
Although the antioxidant and cardioprotective effects of NecroX-5 on various in vitro and in vivo models have been demonstrated, the action of this compound on the mitochondrial oxidative phosphorylation system remains unclear. Here we verify the role of NecroX-5 in protecting mitochondrial oxidative phosphorylation capacity during hypoxia-reoxygenation (HR). Necrox-5 treatment (10 microM) and non-treatment were employed on isolated rat hearts during hypoxia/reoxygenation treatment using an ex vivo Langendorff system. Proteomic analysis was performed using liquid chromatography-mass spectrometry (LC-MS) and non-labeling peptide count protein quantification. Real-time PCR, western blot, citrate synthases and mitochondrial complex activity assays were then performed to assess heart function. Treatment with NecroX-5 during hypoxia significantly preserved electron transport chain proteins involved in oxidative phosphorylation and metabolic functions. NecroX-5 also improved mitochondrial complex I, II, and V function. Additionally, markedly higher peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC1alpha) expression levels were observed in NecroX-5-treated rat hearts. These novel results provide convincing evidence for the role of NecroX-5 in protecting mitochondrial oxidative phosphorylation capacity and in preserving PGC1alpha during cardiac HR injuries.
