Deferoxamine Treatment Combined With Sevoflurane Postconditioning Attenuates Myocardial Ischemia-Reperfusion Injury by Restoring HIF-1/BNIP3-Mediated Mitochondrial Autophagy in GK Rats

Abstract

Mitochondrial autophagy is involved in myocardial protection of sevoflurane postconditioning (SPostC) and in diabetic state this protective effect is weakened due to impaired HIF-1 signaling pathway. Previous studies have proved that deferoxamine (DFO) could activate impaired HIF-1a in diabetic state to restore the cardioprotective of sevoflurane, while the specific mechanism is unclear. This study aims to investigate whether HIF-1/BNIP3-mediated mitochondrial autophagy is involved in the restoration of sevoflurane postconditioning cardioprotection in diabetic state. Ischemia/reperfusion (I/R) model was established by ligating the anterior descending coronary artery and sevoflurane was administered at the first 15 min of reperfusion. Myocardial infarct size, mitochondrial ultrastructure and autophagosome, ATP content, mitochondrial membrane potential, ROS production, HIF-1a, BNIP3, LC3B-II, Beclin-1, P62, LAMP2 protein expression were detected 2 h after reperfusion, and cardiac function was evaluated by ultrasound at 24 h after reperfusion. Our results showed that with DFO treatment, SPostC up-regulated the expression of HIF-1a and BNIP3, thus reduced the expression of key autophagy proteins LC3B-II, Beclin-1, p62, and increased the expression of LAMP2. Furthermore, it reduced the accumulation of autophagosomes and ROS production, increased the content of ATP, and stabilized the membrane potential. Finally, the myocardial infarction size was reduced and cardiac function was improved. Taken together, DFO treatment combined with SPostC could alleviate myocardial ischemia reperfusion injury in diabetic rats by restoring and promoting HIF-1/BNIP3-mediated mitochondrial autophagy.

LncRNA SNHG14 promotes OGD/R-induced neuron injury by inducing excessive mitophagy via miR-182-5p/BINP3 axis in HT22 mouse hippocampal neuronal cells

“…PAR-4 regulates autophagic cell death in human malignant glioma by up-regulating p53 and BNIP3 expression [ 29 ]. Deferoxamine treatment combined with sevoflurane postconditioning improves myocardial ischemia reperfusion injury by regulating HIF-1/BNIP3-mediated mitophagy in diabetic rats [ 30 ]. Thus, these data taken together reveal that SNHG14 overexpression promotes mitophagy of OGD/R-induced HT22 cells by regulating miR-182-5p/BNIP3 axis.…”

The Protective Effect of Aspirin Eugenol Ester on Oxidative Stress to PC12 Cells Stimulated with H2O2 through Regulating PI3K/Akt Signal Pathway

“…As previously reported, the accumulation of ROS can lead to mitochondrial dysfunction by depolarizing mitochondrial membrane potential [ 72 , 73 ]. Mitochondrial membrane potential ( ΔΨ m) is a sensitive index to measure the function of mitochondria [ 74 , 75 ]. The results showed that there was an obvious apoptosis in PC12 cells after H 2 O 2 stimulation, and the cell viability and ΔΨ m decreased.…”

Ginsenoside Re Treatment Attenuates Myocardial Hypoxia/Reoxygenation Injury by Inhibiting HIF-1α Ubiquitination

“…Some HIF-1α-based examples including antioxidation (iNOS), erythropoiesis (EPO) and angiogenesis (VEGF, ENG, LEP), counteract ischemia, hypoxia and promote angiogenesis ( Jain et al, 2018 ). Previous studies demonstrated that HIF-1 activation and upregulation of HIF-1α attenuate myocardial I/R injury ( Yang et al, 2020 ). VHL, a tumor suppressor, functions as part of a ubiquitin ligase complex that recognizes HIF-1α as a substrate and is part of the oxygen-sensing mechanism of the cell ( Vriend and Reiter, 2016 ).…”

“…activation and upregulation of HIF-1a attenuate myocardial I/R injury (Yang et al, 2020). VHL, a tumor suppressor, functions as part of a ubiquitin ligase complex that recognizes HIF-1a as a substrate and is part of the oxygen-sensing mechanism of the cell (Vriend and Reiter, 2016).…”