Ki20227 aggravates apoptosis, inflammatory response, and oxidative stress after focal cerebral ischemia injury

Objective To explore the mechanism of chromobox 7 (CBX7)-mediated nuclear factor E2-related factor 2 (Nrf2)/hemeoxygenase-1 (HO-1) signaling pathway in the cerebral ischemia/reperfusion (I/R) injury. Methods The experimental wild-type (WT) and CBX7-/- mice were used to establish cerebral I/R models using the middle cerebral artery occlusion (MCAO) surgery to determine CBX7 levels at different time points after MCAO injury. For all mice, neurological behavior, infarct size, water content, and oxidative stress–related indicators were determined, and transferase (TdT)-mediated dUTP-biotin nick-end labeling (terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL)) staining method was employed to observe cell apoptosis, while Western blot to measure the expression of CBX7 and Nrf/HO-1 pathway-related proteins. Results At 6 h, 12 h, 24 h, 3 days, and 7 days after mice with MCAO, CBX7 expression was gradually up-regulated and the peak level was reached at 24 h. Mice in the WT + MCAO group had increased infarct size, with significant increases in the modified neurological severity scores and water content in the brain, as well as the quantity of TUNEL-positive cells. For the oxidative stress-indicators, an increase was seen in the content of MDA (malondial dehyde), but the activity of SOD (superoxide dismutase) and content of GSH-PX (glutathione peroxidase) and CAT (catalase) were decreased; meanwhile, the protein expression of CBX7, HO-1, and nuclear Nrf2 was up-regulated, while the cytoplasmic Nrf2 was down-regulated. Moreover, CBX7 knockout attenuated I/R injury in mice. Conclusion Knockout of CBX7 may protect mice from cerebral I/R injury by reducing cell apoptosis and oxidative stress, possibly via activating the Nrf2/HO-1 pathway.

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miR-124-3p targeted SIRT1 to regulate cell apoptosis, inflammatory response, and oxidative stress in acute myocardial infarction in rats via modulation of the FGF21/CREB/PGC1α pathway

Journal of Physiology and Biochemistry ◽

10.1007/s13105-021-00822-z ◽

2021 ◽

Author(s):

Yun-Jie Wei ◽

Jun-Feng Wang ◽

Fei Cheng ◽

Hai-Jun Xu ◽

Jia-Juan Chen ◽

...

Keyword(s):

Oxidative Stress ◽

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Inflammatory Response ◽

Cell Apoptosis ◽

And Oxidative Stress

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Dexmedetomidine inhibits inflammatory response and oxidative stress through regulating miR-205-5p by targeting HMGB1 in cerebral ischemic/reperfusion

Immunopharmacology and Immunotoxicology ◽

10.1080/08923973.2021.1942901 ◽

2021 ◽

pp. 1-9

Author(s):

Jun-jun Yang ◽

Yan-Hong Zhao ◽

Ke-Wen Yin ◽

Xiao-qing Zhang ◽

Jianhui Liu

Keyword(s):

Oxidative Stress ◽

Inflammatory Response ◽

Ischemic Reperfusion ◽

Cerebral Ischemic ◽

Cerebral Ischemic Reperfusion ◽

And Oxidative Stress

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Docosahexaenoic acid reduces cellular inflammatory response following permanent focal cerebral ischemia in rats

The Journal of Nutritional Biochemistry ◽

10.1016/j.jnutbio.2013.08.004 ◽

2013 ◽

Vol 24 (12) ◽

pp. 2127-2137 ◽

Cited By ~ 58

Author(s):

Cheng-Yi Chang ◽

Yu-Hsiang Kuan ◽

Jian-Ri Li ◽

Wen-Ying Chen ◽

Yen-Chuan Ou ◽

...

Keyword(s):

Cerebral Ischemia ◽

Docosahexaenoic Acid ◽

Inflammatory Response ◽

Focal Cerebral Ischemia ◽

Cellular Inflammatory Response

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Cyane-carvone, a Synthetic Derivative of Carvone, Inhibits Inflammatory Response by Reducing Cytokine Production and Oxidative Stress and Shows Antinociceptive Effect in Mice

Inflammation ◽

10.1007/s10753-014-9817-1 ◽

2014 ◽

Author(s):

Thiago Henrique Costa Marques ◽

Maria Leonildes Boavista Gomes Cast Marques ◽

Jand-Venes R. Medeiros ◽

Renan Oliveira Silva ◽

André Luiz dos Reis Barbosa ◽

...

Keyword(s):

Oxidative Stress ◽

Inflammatory Response ◽

Cytokine Production ◽

Antinociceptive Effect ◽

Synthetic Derivative ◽

And Oxidative Stress

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Neuroprotection by Brazilian Green Propolis againstIn vitroandIn vivoIschemic Neuronal Damage

Evidence-based Complementary and Alternative Medicine ◽

10.1093/ecam/neh078 ◽

2005 ◽

Vol 2 (2) ◽

pp. 201-207 ◽

Cited By ~ 56

Author(s):

Masamitsu Shimazawa ◽

Satomi Chikamatsu ◽

Nobutaka Morimoto ◽

Satoshi Mishima ◽

Hiroichi Nagai ◽

...

Keyword(s):

Oxidative Stress ◽

Cerebral Ischemia ◽

Neuronal Damage ◽

Focal Cerebral Ischemia ◽

Brain Infarction ◽

Folk Medicine ◽

Neuroprotective Function ◽

Brazilian Green Propolis

We examined whether Brazilian green propolis, a widely used folk medicine, has a neuroprotective functionin vitroand/orin vivo.In vitro, propolis significantly inhibited neurotoxicity induced in neuronally differentiated PC12 cell cultures by either 24 h hydrogen peroxide (H2O2) exposure or 48 h serum deprivation. Regarding the possible underlying mechanism, propolis protected against oxidative stress (lipid peroxidation) in mouse forebrain homogenates and scavenged free radicals [induced by diphenyl-p-picrylhydrazyl (DPPH). In micein vivo, propolis [30 or 100 mg/kg; intraperitoneally administered four times (at 2 days, 1 day and 60 min before, and at 4 h after induction of focal cerebral ischemia by permanent middle cerebral artery occlusion)] reduced brain infarction at 24 h after the occlusion. Thus, a propolis-induced inhibition of oxidative stress may be partly responsible for its neuroprotective function againstin vitrocell death andin vivofocal cerebral ischemia.

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Lysophosphatidylcholine Offsets the Protective Effects of Bone Marrow Mesenchymal Stem Cells on Inflammatory Response and Oxidative Stress Injury of Retinal Endothelial Cells via TLR4/NF-κB Signaling

Journal of Immunology Research ◽

10.1155/2021/2389029 ◽

2021 ◽

Vol 2021 ◽

pp. 1-10

Author(s):

Haijun Zhao ◽

Yanhui He

Keyword(s):

Oxidative Stress ◽

Stem Cells ◽

Bone Marrow ◽

Endothelial Cells ◽

Inflammatory Response ◽

Protective Effects ◽

Stress Injury ◽

Oxidative Stress Injury ◽

Marrow Mesenchymal Stem Cells ◽

And Oxidative Stress

Diabetic retinopathy (DR), as a major cause of blindness worldwide, is one common complication of diabetes mellitus. Inflammatory response and oxidative stress injury of endothelial cells play significant roles in the pathogenesis of DR. The study is aimed at investigating the effects of lysophosphatidylcholine (LPC) on the dysfunction of high glucose- (HG-) treated human retinal microvascular endothelial cells (HRMECs) after being cocultured with bone marrow mesenchymal stem cells (BMSCs) and the underlying regulatory mechanism. Coculture of BMSCs and HRMECs was performed in transwell chambers. The activities of antioxidant-related enzymes and molecules of oxidative stress injury and the contents of inflammatory cytokines were measured by ELISA. Flow cytometry analyzed the apoptosis of treated HRMECs. HRMECs were further treated with 10-50 μg/ml LPC to investigate the effect of LPC on the dysfunction of HRMECs. Western blotting was conducted to evaluate levels of TLR4 and p-NF-κB proteins. We found that BMSCs alleviated HG-induced inflammatory response and oxidative stress injury of HRMECs. Importantly, LPC offsets the protective effects of BMSCs on inflammatory response and oxidative stress injury of HRMECs. Furthermore, LPC upregulated the protein levels of TLR4 and p-NF-κB, activating the TLR4/NF-κB signaling pathway. Overall, our study demonstrated that LPC offsets the protective effects of BMSCs on inflammatory response and oxidative stress injury of HRMECs via TLR4/NF-κB signaling.

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Oxidative Stress Increases Phosphorylation of IκB Kinase-α by Enhancing NF-κB-Inducing Kinase after Transient Focal Cerebral Ischemia

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2010.6 ◽

2010 ◽

Vol 30 (7) ◽

pp. 1265-1274 ◽

Cited By ~ 15

Author(s):

Yun Seon Song ◽

Min-Soo Kim ◽

Hyun-Ae Kim ◽

Bo-In Jung ◽

Jiwon Yang ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Death ◽

Cerebral Ischemia ◽

Focal Cerebral Ischemia ◽

Nuclear Factor Κb ◽

Nuclear Accumulation ◽

Brain Endothelial Cells ◽

Iκb Kinase ◽

Transient Focal Cerebral Ischemia ◽

Mouse Brain Endothelial Cells

The IκB kinase (IKK) complex is a central component in the classic activation of the nuclear factor-κB (NF-κB) pathway. It has been reported to function in physiologic responses, including cell death and inflammation. We have shown that IKK is regulated by oxidative status after transient focal cerebral ischemia (tFCI) in mice. However, the mechanism by which oxidative stress influences IKKs after tFCI is largely unknown. Nuclear accumulation and phosphorylation of IKKα (pIKKα) were observed 1 h after 30 mins of tFCI in mice. In copper/zinc-superoxide dismutase knockout mice, levels of NF-κB-inducing kinase (NIK) (an upstream kinase of IKKα), pIKKα, and phosphorylation of histone H3 (pH3) on Ser10 were increased after tFCI and were higher than in wild-type mice. Immunohistochemistry showed nuclear accumulation and pIKKα in mouse brain endothelial cells after tFCI. Nuclear factor-κB-inducing kinase was increased, and it enhanced pH3 by inducing pIKKα after oxygen–glucose deprivation (OGD) in mouse brain endothelial cells. Both NIK and pH3 interactions with IKKα were confirmed by coimmunoprecipitation. Treatment with IKKα small interfering RNA significantly reduced cell death after OGD. These results suggest that augmentation of NIK, IKKα, and pH3 in response to oxidative stress is involved in cell death after cerebral ischemia (or stroke).

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