LncRNA SNHG12 Improves Cerebral Ischemic-reperfusion Injury by Activating SIRT1/FOXO3a Pathway through I nhibition of Autophagy and Oxidative Stress

2020 ◽  
Vol 17 (4) ◽  
pp. 394-401
Author(s):  
Yuanhua Wu ◽  
Yuan Huang ◽  
Jing Cai ◽  
Donglan Zhang ◽  
Shixi Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Cell Activity ◽  
Ht22 Cells ◽  
Cerebral Ischemic ◽  
Cerebral Ischemic Reperfusion ◽  
And Oxidative Stress

Background: Ischemia/reperfusion (I/R) injury involves complex biological processes and molecular mechanisms such as autophagy. Oxidative stress plays a critical role in the pathogenesis of I/R injury. LncRNAs are the regulatory factor of cerebral I/R injury. Methods: This study constructs cerebral I/R model to investigate role of autophagy and oxidative stress in cerebral I/R injury and the underline regulatory mechanism of SIRT1/ FOXO3a pathway. In this study, lncRNA SNHG12 and FOXO3a expression was up-regulated and SIRT1 expression was down-regulated in HT22 cells of I/R model. Results: Overexpression of lncRNA SNHG12 significantly increased the cell viability and inhibited cerebral ischemicreperfusion injury induced by I/Rthrough inhibition of autophagy. In addition, the transfected p-SIRT1 significantly suppressed the release of LDH and SOD compared with cells co-transfected with SIRT1 and FOXO3a group and cells induced by I/R and transfected with p-SNHG12 group and overexpression of cells co-transfected with SIRT1 and FOXO3 further decreased the I/R induced release of ROS and MDA. Conclusion: In conclusion, lncRNA SNHG12 increased cell activity and inhibited oxidative stress through inhibition of SIRT1/FOXO3a signaling-mediated autophagy in HT22 cells of I/R model. This study might provide new potential therapeutic targets for further investigating the mechanisms in cerebral I/R injury and provide.

scholarly journals Molecular Mechanisms of Obesity-Linked Cardiac Dysfunction: An Up-Date on Current Knowledge

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 629
Author(s):  
Jorge Gutiérrez-Cuevas ◽  
Ana Sandoval-Rodriguez ◽  
Alejandra Meza-Rios ◽  
Hugo Christian Monroy-Ramírez ◽  
Marina Galicia-Moreno ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Dysfunction ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Peroxisome Proliferator ◽  
White Adipocyte ◽  
Peroxisome Proliferator Activated Receptors ◽  
And Oxidative Stress

Obesity is defined as excessive body fat accumulation, and worldwide obesity has nearly tripled since 1975. Excess of free fatty acids (FFAs) and triglycerides in obese individuals promote ectopic lipid accumulation in the liver, skeletal muscle tissue, and heart, among others, inducing insulin resistance, hypertension, metabolic syndrome, type 2 diabetes (T2D), atherosclerosis, and cardiovascular disease (CVD). These diseases are promoted by visceral white adipocyte tissue (WAT) dysfunction through an increase in pro-inflammatory adipokines, oxidative stress, activation of the renin-angiotensin-aldosterone system (RAAS), and adverse changes in the gut microbiome. In the heart, obesity and T2D induce changes in substrate utilization, tissue metabolism, oxidative stress, and inflammation, leading to myocardial fibrosis and ultimately cardiac dysfunction. Peroxisome proliferator-activated receptors (PPARs) are involved in the regulation of carbohydrate and lipid metabolism, also improve insulin sensitivity, triglyceride levels, inflammation, and oxidative stress. The purpose of this review is to provide an update on the molecular mechanisms involved in obesity-linked CVD pathophysiology, considering pro-inflammatory cytokines, adipokines, and hormones, as well as the role of oxidative stress, inflammation, and PPARs. In addition, cell lines and animal models, biomarkers, gut microbiota dysbiosis, epigenetic modifications, and current therapeutic treatments in CVD associated with obesity are outlined in this paper.

scholarly journals Human INCL fibroblasts display abnormal mitochondrial and lysosomal networks and heightened susceptibility to ROS-induced cell death

2020 ◽  
Author(s):  
Bailey Balouch ◽  
Halle Nagorsky ◽  
Truc Pham ◽  
Thai LaGraff ◽  
Quynh Chu-LaGraff
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Molecular Mechanisms ◽  
Neurodegenerative Disorder ◽  
Endoplasmic Reticulum Stress Response ◽  
Compound Heterozygous ◽  
Storage Material ◽  
Cellular Environment ◽  
And Oxidative Stress

AbstractInfantile Neuronal Ceroid Lipofuscinosis (INCL) is a pediatric neurodegenerative disorder characterized by progressive retinal and central nervous system deterioration during infancy. This lysosomal storage disorder results from a deficiency in the Palmitoyl Protein Thioesterase 1 (PPT1) enzyme - a lysosomal hydrolase which cleaves fatty acid chains such as palmitate from lipid-modified proteins. In the absence of PPT1 activity, these proteins fail to be degraded, leading to the accumulation of autofluorescence storage material in the lysosome. The underlying molecular mechanisms leading to INCL pathology remain poorly understood. A role for oxidative stress has been postulated, yet little evidence has been reported to support this possibility. Here we present a comprehensive cellular characterization of human PPT1-deficient fibroblast cells harboring Met1Ile and Tyr247His compound heterozygous mutations. We detected autofluorescence storage material and observed distinct organellar abnormalities of the lysosomal and mitochondrial structures, which supported previous postulations about the role of ER, mitochondria and oxidative stress in INCL. An increase in the number of lysosomal structures was found in INCL patient fibroblasts, which suggested an upregulation of lysosomal biogenesis, and an association with endoplasmic reticulum stress response. The mitochondrial network also displayed abnormal spherical punctate morphology instead of normal elongated tubules with extensive branching, supporting the involvement of mitochondrial and oxidative stress in INCL cell death. Autofluorescence accumulation and lysosomal pathologies can be mitigated in the presence of conditioned wild type media suggesting that a partial restoration via passive introduction of the enzyme into the cellular environment may be possible. We also demonstrated, for the first time, that human INCL fibroblasts have a heightened susceptibility to exogenous reactive oxygen species (ROS)-induced cell death, which suggested an elevated basal level of endogenous ROS in the mutant cell. Collectively, these findings support the role of intracellular organellar networks in INCL pathology, possibly due to oxidative stress.

FoxO3 transcription factor promotes autophagy after oxidative stress injury in HT22 cells

2020 ◽  
Author(s):  
Aiqing Deng ◽  
Limin Ma ◽  
Xueli Zhou ◽  
Xin Wang ◽  
Shouyan Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transcription Factors ◽  
Cell Injury ◽  
Cell Damage ◽  
Critical Role ◽  
Neuronal Cell ◽  
Ht22 Cells ◽  
Stress Injury ◽  
Oxidative Stress Injury

Autophagy has been implicated in neurodegenerative diseases. Forkhead box O3 (FoxO3) transcription factors promote autophagy in heart and inhibit oxidative damage. Here we investigate the role of FoxO3 transcription factors in regulating autophagy after oxidative stress injury in immortalized mouse hippocampal cell line (HT22). The present study confirms that hydrogen peroxide (H2O2) injury could induce autophagy and FoxO3 activation in HT22 cells. In addition, overexpression of FoxO3 enhanced H2O2-induced autophagy activation and suppressed neuronal cell damage, while knockdown of FoxO3 reduced H2O2-induced autophagy activation and exacerbated neuronal cell injury. Inhibition of autophagy by 3-Methyladenine (3-MA) resulted in reduced cell viability, increased production of reactive oxygen species (ROS), promoted nuclear condensation and decreased expression of antiapoptotic and autophagy-related proteins, indicating that autophagy may have protective effects on H2O2-induced injury in HT22 cells. Moreover, overexpression of FoxO3 prevented exacerbation of brain damage induced by 3-MA. Taken together, these results show that activation of FoxO3 could induce autophagy and inhibit H2O2-induced damage in HT22 cells. Our study demonstrates the critical role of FoxO3 in regulating autophagy in brain.

Critical role of benidipine on bradykinin-eNOS and oxidative stress for cardiac performance in failing rat hearts

2004 ◽  
Vol 10 (5) ◽  
pp. S191
Author(s):  
Mita Shin-Ichiro ◽  
Kobayashi Naohiko ◽  
Honda Takeaki ◽  
Yoshida Kohtaro ◽  
Nakano Shigefumi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Critical Role ◽  
Cardiac Performance ◽  
Rat Hearts ◽  
And Oxidative Stress

scholarly journals Diabetes impairs the protective effects of sevoflurane postconditioning in myocardium subjected to ischemia/reperfusion injury in rats: important role of Drp1

2020 ◽  
Author(s):  
Jing Yu ◽  
Jiandong He ◽  
Wenqu Yang ◽  
Xiang Wang ◽  
Gaoxiang Shi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Infarct Size ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Mitochondrial Fission ◽  
Myocardial Infarct Size ◽  
Diabetic Myocardium ◽  
Sevoflurane Postconditioning ◽  
And Oxidative Stress

Abstract Background Sevoflurane postconditioning (SevP) is an effective way in relieving myocardial ischemia/reperfusion (IR) injury, which doesn’t work well in diabetic myocardium unfortunately. Prior studies have noted the importance of increasing oxidative stress in diabetic tissues. Noteworthily, mitochondrial fission mediated by dynamin-related protein 1 (Drp1) is an upstream pathway of reactive oxygen production. Whether Drp1 dependent mitochondrial fission is associated with the ineffectiveness of SevP in diabetic myocardium remains unknown. The aim of this study was to explore the important role of Drp1 in diabetic myocardium and investigate whether Drp1 inhibition could restore the cardioprotective effect of SevP. Methods In the first part, adult male Sprague-Dawley(SD) rats were divided into 6 groups. Rats in diabetic groups were fed with high-fat and high-sugar for 8 weeks, and then received a injection of streptozotocin (35 mg/kg) intraperitoneally. Myocardial IR was induced by 30 min occlusion of left anterior descending branch of coronary artery followed by 120 min reperfusion༎SevP was applied by continuous inhalation of 2.5% sevoflurane 1 min before reperfusion, which lasted for 10 min. In the second part, mdivi-1 was used to investigate whether Drp1 inhibition could restore the cardioprotective effects of SevP in diabetic myocardium against I/R injury. The myocardial infarct size, pathology, mitochondrial ultrastructure, cardiomyocyte apoptosis, total SOD activity, MDA content, and Drp1 expression were detected. Results The diabetic myocardium displayed severer injury with greater infarct size and apoptosis. Up-regulated Drp1 expression concomitant with increased mitochondrial fission and oxidative stress were observed in diabetic myocardium subjected to I/R. The deteriorated changes were alleviated in normal but not in diabetic rats. Importantly, mdivi-1 administration significantly suppressed mitochondrial fission and oxidative stress, and the beneficial effects of SevP were restored by mdivi-1. Conclusions The present study indicates a crucial role of Drp1 dependent mitochondrial fission in diabetic myocardium subjected to IR. Drp1 inhibition may be effective in restoring the effect of SevP in reducing diabetic myocardial IR injury.

scholarly journals Myocardial Ischemia Reperfusion Injury: Apoptotic, Inflammatory and Oxidative Stress Role of Galectin-3

2018 ◽  
Vol 50 (3) ◽  
pp. 1123-1139 ◽  
Author(s):  
Suhail Al-Salam ◽  
Satwat Hashmi
Keyword(s):  
Oxidative Stress ◽  
Reperfusion Injury ◽  
Troponin I ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Enzyme Linked Immunosorbent Assay ◽  
Wild Type ◽  
Galectin 3 ◽  
And Oxidative Stress

Background/Aims: Myocardial reperfusion has the potential to salvage the ischemic myocardium after a period of coronary occlusion. Reperfusion, however, can cause a wide spectrum of deleterious effects. Galectin-3 (GAL-3), a beta galactoside binding lectin, is closely associated with myocardial infarction (MI), myocardial fibrosis and heart failure. In our study, we investigated its role in ischemia-reperfusion injuries (IR) as this phenomenon is extremely relevant to the early intervention after acute MI. Methods: C57B6/J wild type (WT) mice and GAL-3 knockout (KO) mice were used for murine model of IR injury in the heart where a period of 30 minutes ischemia was followed by 24 hours of reperfusion. Heart samples were processed for immunohistochemical and immunofluorescent labeling, morphometric analysis, western blot and enzyme-linked immunosorbent assay to identify the apoptotic, inflammatory and oxidative stress role of GAL-3. Results: Our results show that there was a significant increase in GAL-3 levels in the heart which shows GAL-3 is playing a role in the ischemia reperfusion injury. Troponin I was also significantly higher in GAL-3-KO group than wild type. Our study shows that GAL-3 is associated with an increase in the antioxidant activity in the IR injured myocardium. Antioxidant enzymes superoxide dismutase, glutathione and catalase were found to be significantly raised in the GAL-3 wild type IR as compared to the GAL-3 KO IR group. A significant increase in apoptotic activity is seen in GAL-3 KO IR group as compared with GAL-3 wild IR group. Conclusion: Our study shows that GAL-3 can affect the redox pathways, controlling cell survival and death, and plays a protective role on the myocardium following IR injury.

scholarly journals Role of Platelet Activation and Oxidative Stress in the Evolution of Myocardial Infarction

2019 ◽  
Vol 24 (6) ◽  
pp. 509-520 ◽  
Author(s):  
Eduardo Fuentes ◽  
Rodrigo Moore-Carrasco ◽  
Antonio Marcus de Andrade Paes ◽  
Andres Trostchansky
Keyword(s):  
Oxidative Stress ◽  
Myocardial Infarction ◽  
Reperfusion Injury ◽  
Antiplatelet Therapy ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion Injury ◽  
Coronary Thrombosis ◽  
Ischemia Reperfusion ◽  
Critical Role

Myocardial infarction, commonly known as heart attack, evolves from the rupture of unstable atherosclerotic plaques to coronary thrombosis and myocardial ischemia–reperfusion injury. A body of evidence supports a close relationship between the alterations following an ischemia–reperfusion injury-induced oxidative stress and platelet activity. Through their critical role in thrombogenesis and inflammatory responses, platelets are fully (totally) implicated from atherothrombotic plaque formation to myocardial infarction onset and expansion. However, mere platelet aggregation prevention does not offer full protection, suggesting that other antiplatelet therapy mechanisms may also be involved. Thus, the present review discusses the integrative role of platelets, oxidative stress, and antiplatelet therapy in triggering myocardial infarction pathophysiology.

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