scholarly journals Inhibiting Cytochrome C Oxidase Leads to Alleviated Ischemia Reperfusion Injury

2017 ◽  
Vol 47 (2) ◽  
pp. 193 ◽  
Author(s):  
Zhaoyun Yang ◽  
Zhongxin Duan ◽  
Tian Yu ◽  
Junmei Xu ◽  
Lei Liu
Keyword(s):  
Cytochrome C ◽  
Reperfusion Injury ◽  
Cytochrome C Oxidase ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion

scholarly journals Brain-Specific Serine-47 Modification of Cytochrome c Regulates Cytochrome c Oxidase Activity Attenuating ROS Production and Cell Death: Implications for Ischemia/Reperfusion Injury and Akt Signaling

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1843 ◽  
Author(s):  
Hasini A. Kalpage ◽  
Junmei Wan ◽  
Paul T. Morse ◽  
Icksoo Lee ◽  
Maik Hüttemann
Keyword(s):  
Cell Death ◽  
Cytochrome C ◽  
Reperfusion Injury ◽  
Cell Line ◽  
Cytochrome C Oxidase ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Ros Generation ◽  
Ros Production ◽  
The Brain

We previously reported that serine-47 (S47) phosphorylation of cytochrome c (Cytc) in the brain results in lower cytochrome c oxidase (COX) activity and caspase-3 activity in vitro. We here analyze the effect of S47 modification in fibroblast cell lines stably expressing S47E phosphomimetic Cytc, unphosphorylated WT, or S47A Cytc. Our results show that S47E Cytc results in partial inhibition of mitochondrial respiration corresponding with lower mitochondrial membrane potentials (ΔΨm) and reduced reactive oxygen species (ROS) production. When exposed to an oxygen-glucose deprivation/reoxygenation (OGD/R) model simulating ischemia/reperfusion injury, the Cytc S47E phosphomimetic cell line showed minimal ROS generation compared to the unphosphorylated WT Cytc cell line that generated high levels of ROS upon reoxygenation. Consequently, the S47E Cytc cell line also resulted in significantly lower cell death upon exposure to OGD/R, confirming the cytoprotective role of S47 phosphorylation of Cytc. S47E Cytc also resulted in lower cell death upon H2O2 treatment. Finally, we propose that pro-survival kinase Akt (protein kinase B) is a likely mediator of the S47 phosphorylation of Cytc in the brain. Akt inhibitor wortmannin abolished S47 phosphorylation of Cytc, while the Akt activator SC79 maintained S47 phosphorylation of Cytc. Overall, our results suggest that loss of S47 phosphorylation of Cytc during brain ischemia drives reperfusion injury through maximal electron transport chain flux, ΔΨm hyperpolarization, and ROS-triggered cell death.

scholarly journals Elevated Serum Potassium Concentration Alleviates Cerebral Ischemia-Reperfusion Injury via Mitochondrial Preservation

2018 ◽  
Vol 48 (4) ◽  
pp. 1664-1674 ◽  
Author(s):  
Nuo Li ◽  
Sina Qin ◽  
Lu Xie ◽  
Tao Qin ◽  
Yegui Yang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Caspase 3 ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Elevated Serum ◽  
Cerebral Ischemia Reperfusion ◽  
Mptp Opening ◽  
Cerebral Ischemia Reperfusion Injury

Background/Aims: The anti-apoptotic effect of an increase in the extracellular concentration of potassium ([K+]) has been confirmed in vitro. However, it is not yet known whether elevated serum [K+] exerts a cerebroprotective effect in vivo. In this study, we aimed to explore the effect of elevated serum [K+] in a rat model of middle cerebral artery occlusion and reperfusion (MCAO/R). Methods: Rats subjected to 90-min MCAO received 2.5% KCL, 1.25% KCL, or a normal saline solution at a dose of 3.2 mL/kg at the onset of reperfusion. Rats that were subjected to vascular exposure and ligation without MCAO were defined as the Sham group. Serum [K+] was determined using a blood gas analyzer at 1 min after medicine administration. At 24 h post-reperfusion, rat brains were harvested and processed for 2% 2,3,5-triphenyltetrazolium chloride staining, terminal deoxynucleotidyl transferase-mediated 2′-deoxyuridine 5′-triphosphate-biotin nick end labeling staining, detection of caspase-3 and cleaved-caspase-3 by western blotting, detection of reactive oxygen species (ROS) by dihydroethidium staining, and observation of mitochondrial structure by electron microscopy. In addition, malondialdehyde (MDA), adenosine triphosphate (ATP), total superoxide dismutase (T-SOD), cytochrome C oxidase (COX) activity, and mitochondrial permeability transition pore (MPTP) opening were measured using detection kits. Results: The results showed that elevated serum [K+] decreased cerebral injury and apoptosis, reduced ROS and MDA levels and MPTP opening, increased ATP levels and cytochrome C oxidase activity, and improved mitochondrial ultrastructural changes, although there was no significant difference in T-SOD activity. Conclusion: These findings suggested that elevated serum [K+] could alleviate cerebral ischemia-reperfusion injury and the mechanism may be associated with the preservation of mitochondrial function.

scholarly journals Kaempferol Alleviates Oxidative Stress and Apoptosis Through Mitochondria-dependent Pathway During Lung Ischemia-Reperfusion Injury

2021 ◽  
Vol 12 ◽  
Author(s):  
Chunli Yang ◽  
Wenkai Yang ◽  
Zhaohui He ◽  
Jinghua Guo ◽  
Xiaogang Yang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cytochrome C ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Alveolar Epithelial Cells ◽  
Mitochondrial Cytochrome ◽  
L2 Cells ◽  
Mitochondrial Cytochrome C

In previous study, we reported that kaempferol ameliorates significantly lung ischemia-reperfusion injury (LIRI), and may be achieved by targeting the SIRT 1 pathway. This study further explored the anti-LIRI mechanism of kaempferol. In vitro, the rat alveolar epithelial cells L2 was cultured and subjected to anoxia/reoxygenation (A/R) insult. In vivo, SD rats were operated to establish LIRI model. The related indicators of oxidative stress and apoptosis in L2 cells and rats lung tissues were detected. Results showed that kaempferol pre-treatment significantly increased the cell viability, improved mitochondrial membrane potential, inhibited the opening of mitochondrial permeability transition pores, reduced the levels of oxidative stress and apoptosis, increased the expressions of Bcl-2 and mitochondrial cytochrome c, and decreased the expressions of Bax and cytoplasmic cytochrome c in L2 cells after A/R insult. In vivo, kaempferol improved the pathological injury, inhibited the levels of oxidative stress and apoptosis, increased the expressions of Bcl-2 and mitochondrial cytochrome c, and decreased the expressions of Bax and cytoplasmic cytochrome c in rats lung tissues after I/R. However, the aforementioned effects of kaempferol were significantly attenuated by the SIRT 1 inhibitor EX527 or the PGC-1α inhibitor SR-18292. What’s more, SR-18292 has not reversed the effect of kaempferol on increasing the protein activity of SIRT 1. Above results suggest that kaempferol ameliorates LIRI by improving mitochondrial function, reducing oxidative stress and inhibiting cell apoptosis. Its molecular mechanism of action includes the SIRT 1/PGC-1α/mitochondria signaling pathway.

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