• Arch. Med. Res. · Feb 2017

    Sphingosine 1-Phosphate Postconditioning Protects Against Myocardial Ischemia/reperfusion Injury in Rats via Mitochondrial Signaling and Akt-Gsk3β Phosphorylation.

    • Rui Fang, Lu-Lu Zhang, Li-Zhi Zhang, Wenchang Li, Mengmeng Li, and Ke Wen.
    • Department of Pharmacology, College of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
    • Arch. Med. Res. 2017 Feb 1; 48 (2): 147-155.

    Background And AimsAlthough preconditioning of sphingosine 1-phosphate (S1P) has been shown to protect myocytes from hypoxia reoxgenation injury in vitro, the role of S1P postconditioning on myocardial ischemia reperfusion injury (MIRI) in vivo and its related mechanism are unknown. The aim of this study was to investigate the protective role of sphingosine 1-phosphate (S1P) postconditioning in MIRI via its effects on mitochondrial signaling and Akt/Gsk3β phosphorylation.MethodsRats were subjected to MIRI, consisting of 30 min of ischemia followed by 120 min of reperfusion, with S1P administered at the beginning of the reperfusion. Myocardial infarct size and apoptotic index were measured by triphenyltetrazolium (TTC) and terminal deoxynucleotide transferase dUTP nick-end labeling (TUNEL) assays, respectively. Akt and Gsk3β phosphorylation, caspase-3 cleavage, and cytochrome c translocation were assessed by western blot. Mitochondrial permeability transition pore (MPTP) opening and mitochondrial membrane potential (MMP, ΔΨ) were also examined to determine overall mitochondrial function.ResultsS1P postconditioning significantly decreased myocardial infarct size and apoptosis, as well as enhanced Akt and Gsk3β phosphorylation, attenuated caspase-3 cleavage and cytosolic cytochrome c translocation, and inhibited MPTP opening, which subsequently preserved Δψ. Electron microscopy also confirmed that S1P helped maintain myocardial mitochondria integrity. Moreover, the protective effects of S1P treatment were blocked by cotreatment with a PI3K inhibitor, LY294002.ConclusionsThese results suggest that S1P postconditioning protects against MIRI by regulating mitochondrial signaling and Akt/Gsk3β phosphorylation.Copyright © 2017 IMSS. Published by Elsevier Inc. All rights reserved.

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