Redox-based regulation of neural stem cell function and Nrf2

2015 ◽  
Vol 43 (4) ◽  
pp. 627-631 ◽  
Author(s):  
Lalitha Madhavan
Keyword(s):  
Oxidative Stress ◽  
Stress Resistance ◽  
Somatic Mutations ◽  
Cell Function ◽  
Therapeutic Potential ◽  
Redox Status ◽  
Common Theme ◽  
Tissue Microenvironment ◽  
Neural Tissues ◽  
Intracellular Redox Status

Neural stem cells (NSCs) play vital roles in the development and maintenance of brain tissues throughout life. They can also potentially act as powerful sources of regeneration and repair during pathology to replace degenerating cells and counteract deleterious changes in the tissue microenvironment. However, both aging and neurodegeneration involve an up-regulation of processes, such as oxidative stress, inflammation, somatic mutations, and reduction in growth factors in neural tissues, which threaten the robust functioning of NSCs. Nevertheless, recent evidence also indicates that NSCs may possess the intrinsic capability to cope with such stressors in their microenvironment. Whereas the mechanisms governing the responses of NSCs to stress are diverse, a common theme that is emerging suggests that underlying changes in intracellular redox status are crucial. Here we discuss such redox-based regulation of NSCs, particularly in relation to nuclear erythroid factor 2-like 2 (Nrf2), which is a key cellular stress resistance factor, and its implications for successfully harnessing NSC therapeutic potential towards developing cell-based therapeutics for nervous system disorders.

scholarly journals Metabolic Implications of Oxidative Stress and Inflammatory Process in SARS-CoV-2 Pathogenesis: Therapeutic Potential of Natural Antioxidants

2021 ◽  
Vol 11 ◽  
Author(s):  
Gilead Ebiegberi Forcados ◽  
Aliyu Muhammad ◽  
Olusola Olalekan Oladipo ◽  
Sunday Makama ◽  
Clement Adebajo Meseko
Keyword(s):  
Oxidative Stress ◽  
Host Cell ◽  
Conformational Changes ◽  
Viral Entry ◽  
Therapeutic Potential ◽  
Natural Antioxidants ◽  
Redox Status ◽  
Response To Therapy ◽  
Innate Immune ◽  
Multiple Signaling

COVID-19 is a zoonotic disease with devastating economic and public health impacts globally. Being a novel disease, current research is focused on a clearer understanding of the mechanisms involved in its pathogenesis and viable therapeutic strategies. Oxidative stress and inflammation are intertwined processes that play roles in disease progression and response to therapy via interference with multiple signaling pathways. The redox status of a host cell is an important factor in viral entry due to the unique conditions required for the conformational changes that ensure the binding and entry of a virus into the host cell. Upon entry into the airways, viral replication occurs and the innate immune system responds by activating macrophage and dendritic cells which contribute to inflammation. This review examines available literature and proposes mechanisms by which oxidative stress and inflammation could contribute to COVID-19 pathogenesis. Further, certain antioxidants currently undergoing some form of trial in COVID-19 patients and the corresponding required research gaps are highlighted to show how targeting oxidative stress and inflammation could ameliorate COVID-19 severity.

scholarly journals Pancreatic angiotensin-converting enzyme 2 improves glycemia in angiotensin II-infused mice

2013 ◽  
Vol 304 (8) ◽  
pp. E874-E884 ◽  
Author(s):  
Kavaljit H. Chhabra ◽  
Huijing Xia ◽  
Kim Brint Pedersen ◽  
Robert C. Speth ◽  
Eric Lazartigues
Keyword(s):  
Oxidative Stress ◽  
Angiotensin Ii ◽  
Cell Function ◽  
Therapeutic Potential ◽  
Renin Angiotensin System ◽  
Ang Ii ◽  
Β Cell ◽  
Mouse Pancreas ◽  
Β Cell Function ◽  
The Impact

An overactive renin-angiotensin system (RAS) is known to contribute to type 2 diabetes mellitus (T2DM). Although ACE2 overexpression has been shown to be protective against the overactive RAS, a role for pancreatic ACE2, particularly in the islets of Langerhans, in regulating glycemia in response to elevated angiotensin II (Ang II) levels remains to be elucidated. This study examined the role of endogenous pancreatic ACE2 and the impact of elevated Ang II levels on the enzyme's ability to alleviate hyperglycemia in an Ang II infusion mouse model. Male C57bl/6J mice were infused with Ang II or saline for a period of 14 days. On the 7th day of infusion, either an adenovirus encoding human ACE2 (Ad-hACE2) or a control adenovirus (Ad-eGFP) was injected into the mouse pancreas. After an additional 7–8 days, glycemia and plasma insulin levels as well as RAS components expression and oxidative stress were assessed. Ang II-infused mice exhibited hyperglycemia, hyperinsulinemia, and impaired glucose-stimulated insulin secretion from pancreatic islets compared with control mice. This phenotype was associated with decreased ACE2 expression and activity, increased Ang II type 1 receptor (AT1R) expression, and increased oxidative stress in the mouse pancreas. Ad-hACE2 treatment restored pancreatic ACE2 expression and compensatory activity against Ang II-mediated impaired glycemia, thus improving β-cell function. Our data suggest that decreased pancreatic ACE2 is a link between overactive RAS and impaired glycemia in T2DM. Moreover, maintenance of a normal endogenous ACE2 compensatory activity in the pancreas appears critical to avoid β-cell dysfunction, supporting a therapeutic potential for ACE2 in controlling diabetes resulting from an overactive RAS.

scholarly journals AβPP-induced UPR Transcriptomic Signature of Glial Cells to Oxidative Stress as an Adaptive Mechanism to Preserve Cell Function and Survival

2018 ◽  
Vol 15 (7) ◽  
pp. 643-654 ◽  
Author(s):  
Naima Chalour ◽  
Agathe Maoui ◽  
Patrice Rat ◽  
France Massicot ◽  
Melody Dutot ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Er Stress ◽  
Cell Function ◽  
Amyloid Β ◽  
Redox Status ◽  
Age Related Macular Degeneration ◽  
Amyloid Β Protein ◽  
Major Genes ◽  
Age Related ◽  
Induced Apoptosis

Background: Alzheimer's disease (AD) and age-related macular degeneration (AMD) present similarities, particularly with respect to oxidative stress, including production of 4-Hydroxy-2- nonenal (HNE). AMD has been named the AD in the eye. The Müller cells (MC) function as a principal glia of the retina and maintain water/potassium, glutamate homeostasis and redox status. Any MC dysfunction results in retinal neurodegeneration. Objectives: We investigated the effects of HNE in human MC. Results: HNE induced an increase of the reactive oxygen species associated with mitochondrial dysfunction and apoptosis. HNE induced endoplasmic reticulum (ER) stress (upregulation of GRP78/Bip, and the proapoptotic factor, CHOP). HNE also impaired expression of genes controlling potassium homeostasis (KCNJ10), glutamate detoxification (GS), and the visual cycle (RLBP1). MC adaptive response to HNE included upregulation of amyloid-β protein precursor (AβPP). To determine the role of AβPP, we overexpressed AβPP in MC. Overexpression of AβPP induced strong antioxidant and anti-ER stress (PERK downregulation and GADD34 upregulation) responses accompanied by activation of the prosurvival branch of the unfolded protein response. It was also associated with upregulation of major genes involved in MC-controlled retinal homeostasis (KCNJ10, GS, and RLBP1) and protection against HNE-induced apoptosis. Therefore, AβPP is an ER and oxidative stress responsive molecule, and is able to stimulate the transcription of major genes involved in MC functions impaired by HNE. Conclusion: Our study suggests that targeting oxidative and ER stress might be a potential therapeutic strategy against glia impairment in AMD and AD, in light of the common features between the two pathologies.

scholarly journals An Overview on the Anti-inflammatory Potential and Antioxidant Profile of Eugenol

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Joice Nascimento Barboza ◽  
Carlos da Silva Maia Bezerra Filho ◽  
Renan Oliveira Silva ◽  
Jand Venes R. Medeiros ◽  
Damião Pergentino de Sousa
Keyword(s):  
Oxidative Stress ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Antioxidant Properties ◽  
Redox Status ◽  
Inhibitory Effect ◽  
New Drugs ◽  
Inflammatory Processes ◽  
Anti Inflammatory

The bioactive compounds found in foods and medicinal plants are attractive molecules for the development of new drugs with action against several diseases, such as those associated with inflammatory processes, which are commonly related to oxidative stress. Many of these compounds have an appreciable inhibitory effect on oxidative stress and inflammatory response, and may contribute in a preventive way to improve the quality of life through the use of a diet rich in these compounds. Eugenol is a natural compound that has several pharmacological activities, action on the redox status, and applications in the food and pharmaceutical industry. Considering the importance of this compound, the present review discusses its anti-inflammatory and antioxidant properties, demonstrating its mechanisms of action and therapeutic potential for the treatment of inflammatory diseases.

Altered intracellular redox status in Gaucher disease fibroblasts and impairment of adaptive response against oxidative stress

2007 ◽  
Vol 212 (1) ◽  
pp. 223-235 ◽  
Author(s):  
Marta Deganuto ◽  
Maria Gabriela Pittis ◽  
Alex Pines ◽  
Silvia Dominissini ◽  
Mark R. Kelley ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Adaptive Response ◽  
Gaucher Disease ◽  
Redox Status ◽  
Intracellular Redox Status ◽  
Intracellular Redox

Canalicular Mrp2 localization is reversibly regulated by the intracellular redox status

2008 ◽  
Vol 295 (5) ◽  
pp. G1035-G1041 ◽  
Author(s):  
Shuichi Sekine ◽  
Kousei Ito ◽  
Toshiharu Horie
Keyword(s):  
Oxidative Stress ◽  
Rat Hepatocytes ◽  
Redox Status ◽  
Intracellular Camp ◽  
Isolated Rat Hepatocytes ◽  
Tertiary Butyl ◽  
Canalicular Membrane ◽  
Internalization Process ◽  
Intracellular Redox Status ◽  
Intracellular Redox

Oxidative stress is known to be a common feature of cholestatic syndrome. We have described the internalization of multidrug resistance-associated protein 2 (Mrp2), a biliary transporter involved in bile salt-independent bile flow, under acute oxidative stress, and a series of signaling pathways finally leading to the activation of novel protein kinase C were involved in this mechanism; however, it has been unclear whether the internalized Mrp2 localization was relocalized to the canalicular membrane when the intracellular redox status was recovered from oxidative stress. In this study, we demonstrated that decreased canalicular expression of Mrp2 induced by tertiary-butyl hydroperoxide (t-BHP) was recovered to the canalicular membrane by the replenishment of GSH by GSH-ethyl ester, a cell-permeable form of GSH. Moreover, pretreatment of isolated rat hepatocytes with colchicine and PKA inhibitor did not affect the t-BHP-induced Mrp2 internalization process but did prevent the Mrp2 recycling process induced by GSH replenishment. Moreover, intracellular cAMP concentration similarly changed with the change of intracellular GSH content. Taken together, our data clearly indicate that the redox-sensitive balance of PKA/PKC activation regulates the reversible Mrp2 localization in two different pathways, the microtubule-independent internalization pathway and -dependent recycling pathway of Mrp2.

scholarly journals A p53-p66Shc signalling pathway controls intracellular redox status, levels of oxidation-damaged DNA and oxidative stress-induced apoptosis

Oncogene ◽  
2002 ◽  
Vol 21 (24) ◽  
pp. 3872-3878 ◽  
Author(s):  
Mirella Trinei ◽  
Marco Giorgio ◽  
Angelo Cicalese ◽  
Sara Barozzi ◽  
Andrea Ventura ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Redox Status ◽  
Signalling Pathway ◽  
Induced Apoptosis ◽  
And Oxidative Stress ◽  
Intracellular Redox Status ◽  
Intracellular Redox ◽  
Damaged Dna

Therapeutic Potential of Vanillin and its Main Metabolites to Regulate the Inflammatory Response and Oxidative Stress

2019 ◽  
Vol 19 (20) ◽  
pp. 1681-1693 ◽  
Author(s):  
Carlos S.M. Bezerra-Filho ◽  
Joice N. Barboza ◽  
Marilia T.S. Souza ◽  
Peter Sabry ◽  
Nasser S.M. Ismail ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Vanillic Acid ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Treatment Strategies ◽  
Redox Status ◽  
Vanillyl Alcohol ◽  
Anti Inflammatory ◽  
Pharmacologically Active ◽  
Pharmacologically Active Compounds

Many phenolic compounds found in foods and medicinal plants have shown interesting therapeutic potential and have attracted the attention of the pharmaceutical industry as promising pharmacologically active compounds in health promotion and disease prevention. Vanillin is a phenolic aldehyde, widely used as a flavoring agent in the food, pharmaceutical, and cosmetics industries. A variety of pharmacological activities has been attributed to this compound and its main metabolites, vanillic acid and vanillyl alcohol, including their anti-inflammatory ability. The relationship of the anti- inflammatory effects of vanillin, vanillic acid, and vanillyl alcohol and their actions on oxidative stress is well established. Considering that the inflammatory process is related to several pathologies, including new diseases with few therapeutic options, and limited efficiency, the search for effective treatment strategies and discovery of new anti-inflammatory agents capable of modulating inflammation becomes necessary. Therefore, in this review, we discuss the therapeutic potential of vanillin and its main metabolites for the treatment of inflammatory diseases and their actions on redox status. In addition, the molecular docking evaluation of vanillin, its metabolites and isoeugenol were carried out into the phospholipase A2 binding site.

scholarly journals The Onset of Tacrolimus Biosynthesis in Streptomyces tsukubaensis Is Dependent on the Intracellular Redox Status

Antibiotics ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 703
Author(s):  
Sílvia D. S. Pires ◽  
Rute Oliveira ◽  
Pedro Moradas-Ferreira ◽  
Marta V. Mendes
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Metabolic Flux ◽  
Redox Status ◽  
Oxidative Stress Response ◽  
Molecular Response ◽  
Streptomyces Tsukubaensis ◽  
The Impact ◽  
Intracellular Redox Status ◽  
Intracellular Redox

The oxidative stress response is a key mechanism that microorganisms have to adapt to changeling environmental conditions. Adaptation is achieved by a fine-tuned molecular response that extends its influence to primary and secondary metabolism. In the past, the role of the intracellular redox status in the biosynthesis of tacrolimus in Streptomyces tsukubaensis has been briefly acknowledged. Here, we investigate the impact of the oxidative stress response on tacrolimus biosynthesis in S. tsukubaensis. Physiological characterization of S. tsukubaensis showed that the onset of tacrolimus biosynthesis coincided with the induction of catalase activity. In addition, tacrolimus displays antioxidant properties and thus a controlled redox environment would be beneficial for its biosynthesis. In addition, S. tsukubaensis ∆ahpC strain, a strain defective in the H2O2-scavenging enzyme AhpC, showed increased production of tacrolimus. Proteomic and transcriptomic studies revealed that the tacrolimus over-production phenotype was correlated with a metabolic rewiring leading to increased availability of tacrolimus biosynthetic precursors. Altogether, our results suggest that the carbon source, mainly used for cell growth, can trigger the production of tacrolimus by modulating the oxidative metabolism to favour a low oxidizing intracellular environment and redirecting the metabolic flux towards the increase availability of biosynthetic precursors.

Sign in / Sign up

Export Citation Format

Share Document