title: NecroX-5 protects mitochondrial oxidative phosphorylation capacity and preserves PGC1α expression levels during hypoxia/reoxygenation injury.
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 µM) 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-1α (PGC1α) 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 PGC1α during cardiac HR injuries.
authors.affiliation: National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan 47392, Korea.; Faculty of Biology, VNU University of Science, Hanoi 120036, Vietnam.
authors.forename: Vu Thi
authors.initials: VT
authors.lastname: Thu
authors.affiliation: National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan 47392, Korea.
authors.forename: Hyoung Kyu
authors.initials: HK
authors.lastname: Kim
authors.affiliation: National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan 47392, Korea.
authors.forename: Le Thanh
authors.initials: le T
authors.lastname: Long
authors.affiliation: National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan 47392, Korea.
authors.forename: Bayalagmaa
authors.initials: B
authors.lastname: Nyamaa
authors.affiliation: National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan 47392, Korea.
authors.forename: In-Sung
authors.initials: IS
authors.lastname: Song
authors.affiliation: Faculty of Biology, VNU University of Science, Hanoi 120036, Vietnam.
authors.forename: To Thanh
authors.initials: TT
authors.lastname: Thuy
authors.affiliation: Faculty of Biology, VNU University of Science, Hanoi 120036, Vietnam.
authors.forename: Nguyen Quang
authors.initials: NQ
authors.lastname: Huy
authors.affiliation: National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan 47392, Korea.
authors.forename: Jubert
authors.initials: J
authors.lastname: Marquez
authors.affiliation: Product Strategy and Development, LG Life Sciences Ltd, Seoul 03184, Korea.
authors.forename: Soon Ha
authors.initials: SH
authors.lastname: Kim
authors.affiliation: National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan 47392, Korea.
authors.forename: Nari
authors.initials: N
authors.lastname: Kim
authors.affiliation: National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan 47392, Korea.
authors.forename: Kyung Soo
authors.initials: KS
authors.lastname: Ko
authors.affiliation: National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan 47392, Korea.
authors.forename: Byoung Doo
authors.initials: BD
authors.lastname: Rhee
authors.affiliation: National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan 47392, Korea.
authors.forename: Jin
authors.initials: J
authors.lastname: Han
keywords: Hypoxia; Mitochondria; NecroX; Oxidative phosphorylation; PCG1α