scholarly journals Idh2 Deficiency Exacerbates Acrolein-Induced Lung Injury through Mitochondrial Redox Environment Deterioration

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Jung Hyun Park ◽  
Hyeong Jun Ku ◽  
Jin Hyup Lee ◽  
Jeen-Woo Park
Keyword(s):  
Oxidative Stress ◽  
Lung Injury ◽  
Knockout Mice ◽  
Cell Injury ◽  
Apoptotic Cell ◽  
Redox Balance ◽  
Redox Status ◽  
Redox Environment ◽  
Protein Thiols

Acrolein is known to be involved in acute lung injury and other pulmonary diseases. A number of studies have suggested that acrolein-induced toxic effects are associated with depletion of antioxidants, such as reduced glutathione and protein thiols, and production of reactive oxygen species. Mitochondrial NADP+-dependent isocitrate dehydrogenase (idh2) regulates mitochondrial redox balance and reduces oxidative stress-induced cell injury via generation of NADPH. Therefore, we evaluated the role of idh2 in acrolein-induced lung injury using idh2 short hairpin RNA- (shRNA-) transfected Lewis lung carcinoma (LLC) cells and idh2-deficient (idh2−/−) mice. Downregulation of idh2 expression increased susceptibility to acrolein via induction of apoptotic cell death due to elevated mitochondrial oxidative stress. Idh2 deficiency also promoted acrolein-induced lung injury in idh2 knockout mice through the disruption of mitochondrial redox status. In addition, acrolein-induced toxicity in idh2 shRNA-transfected LLC cells and in idh2 knockout mice was ameliorated by the antioxidant, N-acetylcysteine, through attenuation of oxidative stress resulting from idh2 deficiency. In conclusion, idh2 deficiency leads to mitochondrial redox environment deterioration, which causes acrolein-mediated apoptosis of LLC cells and acrolein-induced lung injury in idh2−/− mice. The present study supports the central role of idh2 deficiency in inducing oxidative stress resulting from acrolein-induced disruption of mitochondrial redox status in the lung.

scholarly journals SARS-CoV-2 Mediated Endothelial Dysfunction: The Potential Role of Chronic Oxidative Stress

2021 ◽  
Vol 11 ◽  
Author(s):  
Ryan Chang ◽  
Abrar Mamun ◽  
Abishai Dominic ◽  
Nhat-Tu Le
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Lung Injury ◽  
Mitochondrial Dysfunction ◽  
Redox Status ◽  
Feedback Loops ◽  
Chronic Oxidative Stress

Endothelial cells have emerged as key players in SARS-CoV-2 infection and COVID-19 inflammatory pathologies. Dysfunctional endothelial cells can promote chronic inflammation and disease processes like thrombosis, atherosclerosis, and lung injury. In endothelial cells, mitochondria regulate these inflammatory pathways via redox signaling, which is primarily achieved through mitochondrial reactive oxygen species (mtROS). Excess mtROS causes oxidative stress that can initiate and exacerbate senescence, a state that promotes inflammation and chronic endothelial dysfunction. Oxidative stress can also activate feedback loops that perpetuate mitochondrial dysfunction, mtROS overproduction, and inflammation. In this review, we provide an overview of phenotypes mediated by mtROS in endothelial cells – such as mitochondrial dysfunction, inflammation, and senescence – as well as how these chronic states may be initiated by SARS-CoV-2 infection of endothelial cells. We also propose that SARS-CoV-2 activates mtROS-mediated feedback loops that cause long-term changes in host redox status and endothelial function, promoting cardiovascular disease and lung injury after recovery from COVID-19. Finally, we discuss the implications of these proposed pathways on long-term vascular health and potential treatments to address these chronic conditions.

scholarly journals Therapeutic Promise and Principles: Metabotropic Glutamate Receptors

2008 ◽  
Vol 1 (1) ◽  
pp. 1-14 ◽  
Author(s):  
Kenneth Maiese ◽  
Zhao Zhong Chong ◽  
Yan Chen Shang ◽  
Jinling Hou
Keyword(s):  
Oxidative Stress ◽  
Signal Transduction ◽  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Cell Injury ◽  
Apoptotic Cell ◽  
Signal Transduction Pathways ◽  
Metabotropic Glutamate ◽  
Immune System Dysfunction

For a number of disease entities, oxidative stress becomes a significant factor in the etiology and progression of cell dysfunction and injury. Therapeutic strategies that can identify novel signal transduction pathways to ameliorate the toxic effects of oxidative stress may lead to new avenues of treatment for a spectrum of disorders that include diabetes, Alzheimer's disease, Parkinson's disease and immune system dysfunction. In this respect, metabotropic glutamate receptors (mGluRs) may offer exciting prospects for several disorders since these receptors can limit or prevent apoptotic cell injury as well as impact upon cellular development and function. Yet the role of mGluRs is complex in nature and may require specific mGluR modulation for a particular disease entity to maximize clinical efficacy and limit potential disability. Here we discuss the potential clinical translation of mGluRs and highlight the role of novel signal transduction pathways in the metabotropic glutamate system that may be vital for the clinical utility of mGluRs.

scholarly journals Oxidative Stress as a Possible Target in the Treatment of Toxoplasmosis: Perspectives and Ambiguities

2021 ◽  
Vol 22 (11) ◽  
pp. 5705
Author(s):  
Karolina Szewczyk-Golec ◽  
Marta Pawłowska ◽  
Roland Wesołowski ◽  
Marcin Wróblewski ◽  
Celestyna Mila-Kierzenkowska
Keyword(s):  
Oxidative Stress ◽  
Animal Studies ◽  
Treatment Options ◽  
Natural Antioxidants ◽  
Redox Status ◽  
Host Cells ◽  
Common Disease ◽  
Parasite Viability

Toxoplasma gondii is an apicomplexan parasite causing toxoplasmosis, a common disease, which is most typically asymptomatic. However, toxoplasmosis can be severe and even fatal in immunocompromised patients and fetuses. Available treatment options are limited, so there is a strong impetus to develop novel therapeutics. This review focuses on the role of oxidative stress in the pathophysiology and treatment of T. gondii infection. Chemical compounds that modify redox status can reduce the parasite viability and thus be potential anti-Toxoplasma drugs. On the other hand, oxidative stress caused by the activation of the inflammatory response may have some deleterious consequences in host cells. In this respect, the potential use of natural antioxidants is worth considering, including melatonin and some vitamins, as possible novel anti-Toxoplasma therapeutics. Results of in vitro and animal studies are promising. However, supplementation with some antioxidants was found to promote the increase in parasitemia, and the disease was then characterized by a milder course. Undoubtedly, research in this area may have a significant impact on the future prospects of toxoplasmosis therapy.

scholarly journals The Role of Herbal Bioactive Components in Mitochondria Function and Cancer Therapy

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Fangfang Tao ◽  
Yanrong Zhang ◽  
Zhiqian Zhang
Keyword(s):  
Cancer Therapy ◽  
Cancer Cell ◽  
Apoptotic Cell ◽  
Redox Status ◽  
Cancer Therapies ◽  
Bioactive Components ◽  
Atp Production

Mitochondria are highly dynamic double-membrane organelles which play a well-recognized role in ATP production, calcium homeostasis, oxidation-reduction (redox) status, apoptotic cell death, and inflammation. Dysfunction of mitochondria has long been observed in a number of human diseases, including cancer. Targeting mitochondria metabolism in tumors as a cancer therapeutic strategy has attracted much attention for researchers in recent years due to the essential role of mitochondria in cancer cell growth, apoptosis, and progression. On the other hand, a series of studies have indicated that traditional medicinal herbs, including traditional Chinese medicines (TCM), exert their potential anticancer effects as an effective adjunct treatment for alleviating the systemic side effects of conventional cancer therapies, for reducing the risk of recurrence and cancer mortality and for improving the quality of patients’ life. An amazing feature of these structurally diverse bioactive components is that majority of them target mitochondria to provoke cancer cell-specific death program. The aim of this review is to summarize the in vitro and in vivo studies about the role of these herbs, especially their bioactive compounds in the modulation of the disturbed mitochondrial function for cancer therapy.

scholarly journals Potential Role of Epigenetic Mechanism in Manganese Induced Neurotoxicity

2016 ◽  
Vol 2016 ◽  
pp. 1-18 ◽  
Author(s):  
Prashant Tarale ◽  
Tapan Chakrabarti ◽  
Saravanadevi Sivanesan ◽  
Pravin Naoghare ◽  
Amit Bafana ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dna Methyltransferase ◽  
Apoptotic Cell ◽  
Genetic Difference ◽  
Epigenetic Mechanism ◽  
Dna Hypomethylation ◽  
Manganese Neurotoxicity

Manganese is a vital nutrient and is maintained at an optimal level (2.5–5 mg/day) in human body. Chronic exposure to manganese is associated with neurotoxicity and correlated with the development of various neurological disorders such as Parkinson’s disease. Oxidative stress mediated apoptotic cell death has been well established mechanism in manganese induced toxicity. Oxidative stress has a potential to alter the epigenetic mechanism of gene regulation. Epigenetic insight of manganese neurotoxicity in context of its correlation with the development of parkinsonism is poorly understood. Parkinson’s disease is characterized by theα-synuclein aggregation in the form of Lewy bodies in neuronal cells. Recent findings illustrate that manganese can cause overexpression ofα-synuclein.α-Synuclein acts epigenetically via interaction with histone proteins in regulating apoptosis.α-Synuclein also causes global DNA hypomethylation through sequestration of DNA methyltransferase in cytoplasm. An individual genetic difference may also have an influence on epigenetic susceptibility to manganese neurotoxicity and the development of Parkinson’s disease. This review presents the current state of findings in relation to role of epigenetic mechanism in manganese induced neurotoxicity, with a special emphasis on the development of Parkinson’s disease.

The Regulatory Role of MiR-203 in Oxidative Stress induced Cell Injury Through the CBS/H2S Pathway

Nitric Oxide ◽  
2021 ◽  
Author(s):  
Qiuyan Zhang ◽  
Zhuqing Shen ◽  
Yaqi Shen ◽  
Muye Ma ◽  
Hao Jue ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Injury ◽  
Regulatory Role

scholarly journals Nrf2 protects against seawater drowning-induced acute lung injury via inhibiting ferroptosis

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Yu-bao Qiu ◽  
Bin-bin Wan ◽  
Gang Liu ◽  
Ya-xian Wu ◽  
Dan Chen ◽  
...  
Keyword(s):  
Cell Death ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Knockout Mice ◽  
Lipid Peroxide ◽  
Dimethyl Fumarate ◽  
Redox Balance ◽  
Glutathione Depletion ◽  
Stress Injury ◽  
Nrf2 Knockout

Abstract Background Ferroptosis is a new type of nonapoptotic cell death model that was closely related to reactive oxygen species (ROS) accumulation. Seawater drowning-induced acute lung injury (ALI) which is caused by severe oxidative stress injury, has been a major cause of accidental death worldwide. The latest evidences indicate nuclear factor (erythroid-derived 2)-like 2 (Nrf2) suppress ferroptosis and maintain cellular redox balance. Here, we test the hypothesis that activation of Nrf2 pathway attenuates seawater drowning-induced ALI via inhibiting ferroptosis. Methods we performed studies using Nrf2-specific agonist (dimethyl fumarate), Nrf2 inhibitor (ML385), Nrf2-knockout mice and ferroptosis inhibitor (Ferrostatin-1) to investigate the potential roles of Nrf2 on seawater drowning-induced ALI and the underlying mechanisms. Results Our data shows that Nrf2 activator dimethyl fumarate could increase cell viability, reduced the levels of intracellular ROS and lipid ROS, prevented glutathione depletion and lipid peroxide accumulation, increased FTH1 and GPX4 mRNA expression, and maintained mitochondrial membrane potential in MLE-12 cells. However, ML385 promoted cell death and lipid ROS production in MLE-12 cells. Furthermore, the lung injury became more aggravated in the Nrf2-knockout mice than that in WT mice after seawater drowning. Conclusions These results suggested that Nrf2 can inhibit ferroptosis and therefore alleviate ALI induced by seawater drowning. The effectiveness of ferroptosis inhibition by Nrf2 provides a novel therapeutic target for seawater drowning-induced ALI.

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