scholarly journals The Circadian Clock Regulates the Expression of the Nuclear Factor Erythroid 2-Related Factor 2 in Acute Kidney Injury following Myocardial Ischemia-Reperfusion in Diabetic Rat

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Chong Dong ◽  
Cheng Zeng ◽  
Li Du ◽  
Qian Sun
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Myocardial Ischemia ◽  
Circadian Clock ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Diabetic Rat ◽  
Related Factor ◽  
Nuclear Factor ◽  
Myocardial Ischemia Reperfusion

Cardiac surgery-associated acute kidney injury (AKI) is a serious and frequent complication with poor prognosis, and disruption in circadian rhythm shall adversely influence cardiovascular and renal functions via oxidative stress mechanisms. However, the role of circadian clock genes (circadian locomotor output cycle kaput (CLOCK) and brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein-1 (BMAL1)) and its interaction with nuclear factor erythroid 2-related factor 2 (Nrf2) in AKI following myocardial ischemia-reperfusion (MIR) in the diabetic rat has not yet been explored. In this study, rats were divided into the sham (S) group, MIR (M) group, diabetic (D) group, and diabetic+MIR (DM) group. At light (zeitgeber time (ZT) 0) and dark time points (ZT12), rat MIR model was established by occlusion of the left anterior descending coronary artery for 30 min followed by 2 -hour reperfusion, and then renal injury was evaluated. The renal histological changes in the DM group were significantly high compared to other groups; serum creatinine, blood urea nitrogen, and neutrophil gelatinase-associated lipocalin levels, as well as malondialdehyde and 8-iso-prostaglandin-F2α levels in renal tissues of M ZT12 and DM ZT12 subgroups, were significantly higher than those of M ZT0 and DM ZT0 subgroups, individually indicating increased oxidative stress at a dark cycle. Further, Nrf2 protein accumulated in a circadian manner with decreasing levels at night in the DM and M groups. In conclusion, renal injury following MIR was exacerbated in the diabetic rat at night through molecular mechanisms involving transcriptional control of the circadian clock on light-dark activation of Nrf2.

Sestrin2 is involved in Nrf2-regulated antioxidative signaling pathway in luteolin-induced prevention of the diabetic rat heart from ischemia/reperfusion injury

2021 ◽  
Author(s):  
Xin-Ru Zhou ◽  
Xiao-Chen Ru ◽  
Chi Xiao ◽  
Jie Pan ◽  
Yang-Yun Lou ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Rat Heart ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Diabetic Rat ◽  
Related Factor ◽  
Nuclear Factor ◽  
Inducible Protein ◽  
Myocardial Ischemia Reperfusion

Luteolin attenuates myocardial ischemia/reperfusion (I/R) injury in diabetes through activating nuclear factor erythroid 2-related factor 2 (Nrf2)-related antioxidative response. Though sestrin2, a highly conserved stress-inducible protein, is regarded as a...

scholarly journals microRNA-130a-5p suppresses myocardial ischemia reperfusion injury by downregulating the HMGB2/NF-κB axis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yong Li ◽  
Hongbo Zhang ◽  
Zhanhu Li ◽  
Xiaoju Yan ◽  
Yuan Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Mouse Models ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Luciferase Reporter ◽  
Gene Assay ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Abstract Background Myocardial ischemia reperfusion injury (MIRI) is defined as tissue injury in the pathological process of progressive aggravation in ischemic myocardium after the occurrence of acute coronary artery occlusion. Research has documented the involvement of microRNAs (miRs) in MIRI. However, there is obscure information about the role of miR-130a-5p in MIRI. Herein, this study aims to investigate the effect of miR-130a-5p on MIRI. Methods MIRI mouse models were established. Then, the cardiac function and hemodynamics were detected using ultrasonography and multiconductive physiological recorder. Functional assays in miR-130a-5p were adopted to test the degrees of oxidative stress, mitochondrial functions, inflammation and apoptosis. Hematoxylin and eosin (HE) staining was performed to validate the myocardial injury in mice. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was employed to assess the expression patterns of miR-130a-5p, high mobility group box (HMGB)2 and NF-κB. Then, dual-luciferase reporter gene assay was performed to elucidate the targeting relation between miR-130a-5p and HMGB2. Results Disrupted structural arrangement in MIRI mouse models was evident from HE staining. RT-qPCR revealed that overexpressed miR-130a-5p alleviated MIRI, MIRI-induced oxidative stress and mitochondrial disorder in the mice. Next, the targeting relation between miR-130a-5p and HMGB2 was ascertained. Overexpressed HMGB2 annulled the protective effects of miR-130a-5p in MIRI mice. Additionally, miR-130a-5p targets HMGB2 to downregulate the nuclear factor kappa-B (NF-κB) axis, mitigating the inflammatory injury induced by MIRI. Conclusion Our study demonstrated that miR-130a-5p suppresses MIRI by down-regulating the HMGB2/NF-κB axis. This investigation may provide novel insights for development of MIRI treatments.

Neuroprotection of chromobox 7 knockout in the mouse after cerebral ischemia-reperfusion injury via nuclear factor E2-related factor 2/hemeoxygenase-1 signaling pathway

2021 ◽  
pp. 096032712110361
Author(s):  
Hai-Tao Zhang ◽  
Xi-Zeng Wang ◽  
Qing-Mei Zhang ◽  
Han Zhao
Keyword(s):  
Oxidative Stress ◽  
Cerebral Ischemia ◽  
Infarct Size ◽  
Water Content ◽  
Cell Apoptosis ◽  
Ischemia Reperfusion ◽  
Related Factor ◽  
Nuclear Factor ◽  
Cerebral Ischemia Reperfusion ◽  
And Oxidative Stress

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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