scholarly journals Quercetin Improves Cardiomyocyte Vulnerability to Hypoxia by Regulating SIRT1/TMBIM6-Related Mitophagy and Endoplasmic Reticulum Stress

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Xing Chang ◽  
Tian Zhang ◽  
Qingyan Meng ◽  
ShiyuanWang ◽  
Peizheng Yan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Endoplasmic Reticulum ◽  
Cardiovascular Diseases ◽  
Endoplasmic Reticulum Stress ◽  
Oxygen Species ◽  
Protective Effects ◽  
Hypoxic Injury ◽  
Human Cardiomyocytes ◽  
Stress Damage

Cardiomyocyte apoptosis is an important pathological mechanism underlying cardiovascular diseases and is commonly caused by hypoxia. Moreover, hypoxic injury occurs not only in common cardiovascular diseases but also following various treatments of heart-related conditions. One of the major mechanisms underlying hypoxic injury is oxidative stress. Quercetin has been shown to exert antioxidant stress and vascular protective effects, making it a promising candidate for treating cardiovascular diseases. Therefore, we examined the protective effect of quercetin on human cardiomyocytes subjected to hypoxia-induced oxidative stress damage and its underlying mechanism. Human cardiomyocytes were subjected to hypoxia/reoxygenation (H/R) in vitro with or without quercetin pretreatment; thereafter, flow cytometry, Cell Counting Kit-8 assay, laser scanning confocal microscopy, quantitative PCR, western blotting, and enzyme-linked immunosorbent assay were performed to analyze the effects of quercetin on cardiomyocytes. We found that H/R induced reactive oxygen species overproduction and endoplasmic reticulum stress, as well as inhibited the function of the mitochondria/endoplasmic reticulum and mitophagy, eventually leading to apoptosis and decreasing the viability of human cardiomyocytes. Quercetin pretreatment inhibited H/R-mediated overproduction of reactive oxygen species and damage caused by oxidative stress, increased mitophagy, regulated mRNA and protein expression of transmembrane BAX inhibitor-1 motif-containing 6 (TMBIM6), regulated endoplasmic reticulum stress, and improved the vulnerability of human cardiomyocytes to H/R. Furthermore, transfection with short interfering RNA against silent information regulator protein 1 (SIRT1) counteracted the protective effects of quercetin on cardiomyocytes. Thus, quercetin was predicted to regulate mitophagy and endoplasmic reticulum stress through SIRT1/TMBIM6 and inhibit H/R-induced oxidative stress damage. These findings may be useful for developing treatments for hypoxic injury-induced cardiovascular diseases and further highlight the potential of quercetin for regulating mitochondrial quality control and endoplasmic reticulum function.

scholarly journals Reactive Oxygen Species-Triggered Trophoblast Apoptosis Is Initiated by Endoplasmic Reticulum Stress via Activation of Caspase-12, CHOP, and the JNK Pathway in Toxoplasma gondii Infection in Mice

2012 ◽  
Vol 80 (6) ◽  
pp. 2121-2132 ◽  
Author(s):  
Xiucai Xu ◽  
Tingting Liu ◽  
Aimei Zhang ◽  
Xingxing Huo ◽  
Qingli Luo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Endoplasmic Reticulum ◽  
Toxoplasma Gondii ◽  
Endoplasmic Reticulum Stress ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Jnk Pathway ◽  
Content Type ◽  
Caspase 12

ABSTRACTToxoplasma gondiiinfection in pregnant women may result in abortion or in fetal teratogenesis; however, the underlying mechanisms are still unclear. In this paper, based on a murine model, we showed that maternal infection with RH strainT. gondiitachyzoites induced elevated production of reactive oxygen species (ROS), local oxidative stress, and subsequent apoptosis of placental trophoblasts. PCR array analysis of 84 oxidative stress-related genes demonstrated that 27 genes were upregulated at least 2-fold and that 9 genes were downregulated at least 2-fold in theT. gondiiinfection group compared with levels in the control group. The expression of NADPH oxidase 1 (Nox1) and glutathione peroxidase 6 (Gpx6) increased significantly, about 25-fold. The levels of malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-OHdG) increased significantly withT. gondiiinfection, and levels of glutathione (GSH) decreased rapidly.T. gondiiinfection increased the early expression of endoplasmic reticulum stress (ERS) markers, followed by cleavage of caspase-12, activation of ASK1/JNK, and increased apoptosis of trophoblasts, bothin vivoandin vitro. The apoptosis of trophoblasts, the activation of caspase-12 and the ASK1/JNK pathway, and the production of peroxides were dramatically inhibited by pretreatment withN-acetylcysteine (NAC). The upregulation of Nox1 was contact dependent and preceded the increase in levels of ERS markers and the activation of the proapoptosis cascade. Thus, we concluded that apoptosis in placental trophoblasts was initiated predominantly by ROS-mediated ERS via activation of caspase-12, CHOP, and the JNK pathway in acuteT. gondiiinfection. Elevated ROS production is the central event inT. gondii-induced apoptosis of placental trophoblasts.

scholarly journals hAMSC-CM Attenuates Paraquat-Induced A549 Cell Damage by Reducing Endoplasmic Reticulum Stress and Oxidative Stress

2021 ◽  
Author(s):  
Futuan Liao ◽  
Liming Gong ◽  
Lijing Jia ◽  
Jianhong Wang ◽  
Tongying Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Cell Damage ◽  
Intervention Group ◽  
A549 Cells ◽  
Protective Effects ◽  
Stress Oxidative ◽  
Stress Damage ◽  
And Oxidative Stress

Abstract Acute paraquat (PQ) poisoning results in severe acute lung injury and pulmonary fibrosis, and there is no specific antidote; thus, the mortality rate of PQ poisoning is extremely high. The mechanism of poisoning may be associated with endoplasmic reticulum stress, oxidative stress damage and organ/tissue inflammation. Recent studies have reported that human amnion-derived mesenchymal stem cells (hAMSCs) secrete a variety of cytokines, and that hAMSC-conditioned medium (CM) has anti-inflammatory and immunomodulatory effects. The aim of the present study was to investigate whether hAMSC-CM exerts protective effects against PQ toxicity in A549 cells. The data demonstrated that the activity of A549 cells was decreased after 24 h of PQ exposure and that the cell viability of the hAMSC-CM intervention group was higher compared with the PQ-only group. hAMSC-CM intervention decreased cell damage, apoptosis rates, oxidative stress indexes, Bax/Bcl-2 ratios and CHOP expression levels in poisoned cells by CCK-8 experiment, apoptosis detection, ROS content detection, and Western blot analysis respectively. In conclusion, hAMSC-CM may attenuate the cell damage caused by PQ by reducing endoplasmic reticulum stress and oxidative stress.

scholarly journals Intracellular Sources of ROS/H2O2 in Health and Neurodegeneration: Spotlight on Endoplasmic Reticulum

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 233
Author(s):  
Tasuku Konno ◽  
Eduardo Pinho Melo ◽  
Joseph E. Chambers ◽  
Edward Avezov
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Hydrogen Peroxide ◽  
Endoplasmic Reticulum ◽  
Neurodegenerative Diseases ◽  
Antioxidative Enzymes ◽  
Redox Reactions ◽  
Ros Production ◽  
Oxygen Species ◽  
Specific Target

Reactive oxygen species (ROS) are produced continuously throughout the cell as products of various redox reactions. Yet these products function as important signal messengers, acting through oxidation of specific target factors. Whilst excess ROS production has the potential to induce oxidative stress, physiological roles of ROS are supported by a spatiotemporal equilibrium between ROS producers and scavengers such as antioxidative enzymes. In the endoplasmic reticulum (ER), hydrogen peroxide (H2O2), a non-radical ROS, is produced through the process of oxidative folding. Utilisation and dysregulation of H2O2, in particular that generated in the ER, affects not only cellular homeostasis but also the longevity of organisms. ROS dysregulation has been implicated in various pathologies including dementia and other neurodegenerative diseases, sanctioning a field of research that strives to better understand cell-intrinsic ROS production. Here we review the organelle-specific ROS-generating and consuming pathways, providing evidence that the ER is a major contributing source of potentially pathologic ROS.

scholarly journals Sources of ROS Species an Its Harmful and Benefical Effects on Human Health

2021 ◽  
Author(s):  
Sidra Munir
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Antioxidant Enzymes ◽  
Immune System ◽  
Cardiovascular Diseases ◽  
Partial Oxidation ◽  
Human Body ◽  
Therapeutic Potential ◽  
Oxygen Species ◽  
Essential Function

When the antioxidants in our immune system cannot neutralize or convert Reactive oxygen species into safe molecules at the rate at which it is produced then this imbalance is termed as “oxidative stress”. It is related with a wide array of diseases that includes cancer, diabetes, cardiovascular diseases, hypertension etc. These ROS species however are utmost essential for the proper functioning of human body which are produced as a consequence of partial oxidation of cellular metabolism performing essential functions such as protein phosphorylation, activation of several transcriptional factors, apoptosis, immunity, and differentiation. The sources by which these are produced can be broadly classified are intrinsic and extrinsic sources. There are variety of natural antioxidant enzymes of human body that combat against this oxidative stress. The extrinsic sources of ROS include the use of natural plants, extracted flavonoids and vitamins. In this review we will briefly explain how the sources of ROS, its essential function in human body, its elevation and associated damage to organs and effect on various diseases, and a hope of finding a way of how this oxidative stress can be exploited for therapeutic potential.

scholarly journals Use of Exogenous and Endogenous Photomediators as Efficient ROS Modulation Tools: Results and Perspectives for Therapeutic Purposes

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Maria Rosa Antognazza ◽  
Ilaria Abdel Aziz ◽  
Francesco Lodola
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Cardiovascular Diseases ◽  
Fluorescent Probes ◽  
State Of The Art ◽  
Polymeric Materials ◽  
Living Systems ◽  
Oxygen Species ◽  
Recent Developments ◽  
Long Time

Reactive Oxygen Species (ROS) play an essential dual role in living systems. Healthy levels of ROS modulate several signaling pathways, but at the same time, when they exceed normal physiological amounts, they work in the opposite direction, playing pivotal functions in the pathophysiology of multiple severe medical conditions (i.e., cancer, diabetes, neurodegenerative and cardiovascular diseases, and aging). Therefore, the research for methods to detect their levels via light-sensitive fluorescent probes has been extensively studied over the years. However, this is not the only link between light and ROS. In fact, the modulation of ROS mediated by light has been exploited already for a long time. In this review, we report the state of the art, as well as recent developments, in the field of photostimulation of oxidative stress, from photobiomodulation (PBM) mediated by naturally expressed light-sensitive proteins to the most recent optogenetic approaches, and finally, we describe the main methods of exogenous stimulation, in particular highlighting the new insights based on optically driven ROS modulation mediated by polymeric materials.

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