Activation of the ACE2/Ang-(1–7)/Mas pathway reduces oxygen–glucose deprivation-induced tissue swelling, ROS production, and cell death in mouse brain with angiotensin II overproduction

Kaempferol has been shown to protect cells against cerebral ischemia/reperfusion injury through inhibition of apoptosis. In the present study, we sought to investigate whether ferroptosis is involved in the oxygen-glucose deprivation/reperfusion (OGD/R)-induced neuronal injury and the effects of kaempferol on ferroptosis in OGD/R-treated neurons. Western blot, immunofluorescence, and transmission electron microscopy were used to analyze ferroptosis, whereas cell death was detected using lactate dehydrogenase (LDH) release. We found that OGD/R attenuated SLC7A11 and glutathione peroxidase 4 (GPX4) levels as well as decreased endogenous antioxidants including nicotinamide adenine dinucleotide phosphate (NADPH), glutathione (GSH), and superoxide dismutase (SOD) in neurons. Notably, OGD/R enhanced the accumulation of lipid peroxidation, leading to the induction of ferroptosis in neurons. However, kaempferol activated nuclear factor-E2-related factor 2 (Nrf2)/SLC7A11/GPX4 signaling, augmented antioxidant capacity, and suppressed the accumulation of lipid peroxidation in OGD/R-treated neurons. Furthermore, kaempferol significantly reversed OGD/R-induced ferroptosis. Nevertheless, inhibition of Nrf2 by ML385 blocked the protective effects of kaempferol on antioxidant capacity, lipid peroxidation, and ferroptosis in OGD/R-treated neurons. These results suggest that ferroptosis may be a significant cause of cell death associated with OGD/R. Kaempferol provides protection from OGD/R-induced ferroptosis partly by activating Nrf2/SLC7A11/GPX4 signaling pathway.

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Cytosolic Guanine Nucledotide Binding Deficient Form of Transglutaminase 2 (R580a) Potentiates Cell Death in Oxygen Glucose Deprivation

PLoS ONE ◽

10.1371/journal.pone.0016665 ◽

2011 ◽

Vol 6 (1) ◽

pp. e16665 ◽

Cited By ~ 24

Author(s):

Gozde Colak ◽

Jeffrey W. Keillor ◽

Gail V. W. Johnson

Keyword(s):

Cell Death ◽

Transglutaminase 2 ◽

Glucose Deprivation ◽

Oxygen Glucose Deprivation

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BID mediates neuronal cell death after oxygen/ glucose deprivation and focal cerebral ischemia

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.261323298 ◽

2001 ◽

Vol 98 (26) ◽

pp. 15318-15323 ◽

Cited By ~ 171

Author(s):

N. Plesnila ◽

S. Zinkel ◽

D. A. Le ◽

S. Amin-Hanjani ◽

Y. Wu ◽

...

Keyword(s):

Cell Death ◽

Cerebral Ischemia ◽

Focal Cerebral Ischemia ◽

Neuronal Cell Death ◽

Neuronal Cell ◽

Glucose Deprivation ◽

Oxygen Glucose Deprivation

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NQO1-induced activation of AMPK contributes to cancer cell death by oxygen-glucose deprivation

Scientific Reports ◽

10.1038/srep07769 ◽

2015 ◽

Vol 5 (1) ◽

Cited By ~ 13

Author(s):

Hyemi Lee ◽

Eun-Taex Oh ◽

Bo-Hwa Choi ◽

Moon-Taek Park ◽

Ja-Kyeong Lee ◽

...

Keyword(s):

Cell Death ◽

Cancer Cell ◽

Glucose Deprivation ◽

Oxygen Glucose Deprivation ◽

Cancer Cell Death

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Pre- or Postinsult Administration of Lidocaine or Thiopental Attenuates Cell Death in Rat Hippocampal Slice Cultures Caused by Oxygen-Glucose Deprivation

Anesthesia & Analgesia ◽

10.1213/01.ane.0000167268.61051.41 ◽

2005 ◽

Vol 101 (4) ◽

pp. 1163-1169 ◽

Cited By ~ 17

Author(s):

Hong Cao ◽

Ira S. Kass ◽

James E. Cottrell ◽

Peter J. Bergold

Keyword(s):

Cell Death ◽

Hippocampal Slice ◽

Glucose Deprivation ◽

Oxygen Glucose Deprivation ◽

Hippocampal Slice Cultures

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Costunolide attenuates oxygen-glucose deprivation/reoxygenation-induced apoptosis in mouse brain slice through inhibiting caspase expression

Pharmacognosy Magazine ◽

10.4103/pm.pm_360_20 ◽

2021 ◽

Vol 17 (74) ◽

pp. 231

Author(s):

Xinhui Zhang ◽

Qipeng Zhao ◽

Huixia Ma ◽

Yafei Zhu ◽

Zhengjun Zhang

Keyword(s):

Mouse Brain ◽

Brain Slice ◽

Glucose Deprivation ◽

Oxygen Glucose Deprivation ◽

Induced Apoptosis

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Ginsenosides Rb1 and Rg1 Protect Primary Cultured Astrocytes against Oxygen-Glucose Deprivation/Reoxygenation-Induced Injury via Improving Mitochondrial Function

International Journal of Molecular Sciences ◽

10.3390/ijms20236086 ◽

2019 ◽

Vol 20 (23) ◽

pp. 6086 ◽

Cited By ~ 8

Author(s):

Meng Xu ◽

Qing Ma ◽

Chunlan Fan ◽

Xue Chen ◽

Huiming Zhang ◽

...

Keyword(s):

Oxidative Phosphorylation ◽

Cell Viability ◽

Mitochondrial Function ◽

Copy Number ◽

Glucose Deprivation ◽

Oxygen Glucose Deprivation ◽

Ros Production ◽

Protective Effects ◽

Mtdna Copy Number ◽

Cultured Astrocytes

This study aimed to evaluate whether ginsenosides Rb1 (20-S-protopanaxadiol aglycon) and Rg1 (20-S-protopanaxatriol aglycon) have mitochondrial protective effects against oxygen-glucose deprivation/reoxygenation (OGD/R)-induced injury in primary mouse astrocytes and to explore the mechanisms involved. The OGD/R model was used to mimic the pathological process of cerebral ischemia-reperfusion in vitro. Astrocytes were treated with normal conditions, OGD/R, OGD/R plus Rb1, or OGD/R plus Rg1. Cell viability was measured to evaluate the cytotoxicity of Rb1 and Rg1. Intracellular reactive oxygen species (ROS) and catalase (CAT) were detected to evaluate oxidative stress. The mitochondrial DNA (mtDNA) copy number and mitochondrial membrane potential (MMP) were measured to evaluate mitochondrial function. The activities of the mitochondrial respiratory chain (MRC) complexes I–V and the level of cellular adenosine triphosphate (ATP) were measured to evaluate oxidative phosphorylation (OXPHOS) levels. Cell viability was significantly decreased in the OGD/R group compared to the control group. Rb1 or Rg1 administration significantly increased cell viability. Moreover, OGD/R caused a significant increase in ROS formation and, subsequently, it decreased the activity of CAT and the mtDNA copy number. At the same time, treatment with OGD/R depolarized the MMP in the astrocytes. Rb1 or Rg1 administration reduced ROS production, increased CAT activity, elevated the mtDNA content, and attenuated the MMP depolarization. In addition, Rb1 or Rg1 administration increased the activities of complexes I, II, III, and V and elevated the level of ATP, compared to those in the OGD/R groups. Rb1 and Rg1 have different chemical structures, but exert similar protective effects against astrocyte damage induced by OGD/R. The mechanism may be related to improved efficiency of mitochondrial oxidative phosphorylation and the reduction in ROS production in cultured astrocytes.

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Eye Opener in Stroke

Stroke ◽

10.1161/strokeaha.119.025249 ◽

2019 ◽

Vol 50 (8) ◽

pp. 2197-2206 ◽

Cited By ~ 6

Author(s):

Hung Nguyen ◽

Jea Young Lee ◽

Paul R. Sanberg ◽

Eleonora Napoli ◽

Cesar V. Borlongan

Keyword(s):

Cell Death ◽

Mitochondrial Dysfunction ◽

Glucose Deprivation ◽

Retinal Ischemia ◽

Artery Occlusion ◽

Oxygen Glucose Deprivation ◽

Retinal Pigmented Epithelium ◽

Pigmented Epithelium ◽

Cerebral Artery Occlusion ◽

Epithelium Cells

Background and Purpose— Retinal ischemia is a major cause of visual impairment in stroke patients, but our incomplete understanding of its pathology may contribute to a lack of effective treatment. Here, we investigated the role of mitochondrial dysfunction in retinal ischemia and probed the potential of mesenchymal stem cells (MSCs) in mitochondrial repair under such pathological condition. Methods— In vivo, rats were subjected to middle cerebral artery occlusion then randomly treated with intravenous MSCs or vehicle. Laser Doppler was used to evaluate the blood flow in the brain and the eye, while immunohistochemical staining assessed cellular degeneration at days 3 and 14 poststroke. In vitro, retinal pigmented epithelium cells were exposed to either oxygen-glucose deprivation or oxygen-glucose deprivation and coculture with MSCs, and subsequently, cell death and mitochondrial function were examined immunocytochemically and with Seahorse analyzer, respectively. Results— Middle cerebral artery occlusion significantly reduced blood flow in the brain and the eye accompanied by mitochondrial dysfunction and ganglion cell death at days 3 and 14 poststroke. Intravenous MSCs elicited mitochondrial repair and improved ganglion cell survival at day 14 poststroke. Oxygen-glucose deprivation similarly induced mitochondrial dysfunction and cell death in retinal pigmented epithelium cells; coculture with MSCs restored mitochondrial respiration, mitochondrial network morphology, and mitochondrial dynamics, which likely attenuated oxygen-glucose deprivation-mediated retinal pigmented epithelium cell death. Conclusions— Retinal ischemia is closely associated with mitochondrial dysfunction, which can be remedied by stem cell-mediated mitochondrial repair.

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