scholarly journals Sestrins as modulators of aging processes and diseases related to age

2021 ◽  
Vol 75 ◽  
pp. 437-447
Author(s):  
Bożena Gabryel ◽  
Roksana Duszkiewicz
Keyword(s):  
Metabolic Disorders ◽  
Cell Metabolism ◽  
Genotoxic Stress ◽  
Protective Role ◽  
Mechanisms Of Action ◽  
Oxygen Species ◽  
Age Related ◽  
Regulate Cell Growth ◽  
Growth Metabolism ◽  
Amp Activated Protein Kinase

Sestrins are highly conserved proteins that regulate cell growth, metabolism, survival and proliferation under oxidative stress, genotoxic stress, hypoxia or endoplasmic reticulum stress. Sestrins affect cell signaling by inhibiting the production of reactive oxygen species, activating the AMP-activated protein kinase (AMPK), inhibiting the mTOR pathway and acting as a positive regulator of autophagy. Therefore, their protective role against cancer, metabolic disorders, cardiovascular diseases and neurodegeneration is increasingly being postulated. The article describes the mechanisms of action of sestrins and their meaning in aging and age-related diseases. The latest studies indicating their physiological significance and role in key signaling pathways controlling the cell metabolism and survival under stress conditions were also discussed.

scholarly journals Nicotinamide as a Foundation for Treating Neurodegenerative Disease and Metabolic Disorders

2021 ◽  
Vol 17 ◽  
Author(s):  
Kenneth Maiese
Keyword(s):  
Metabolic Disease ◽  
Neurodegenerative Disorders ◽  
Metabolic Disorders ◽  
Lactate Production ◽  
Cellular Protection ◽  
Innovative Strategies ◽  
Forkhead Transcription Factors ◽  
Age Related ◽  
Promising Target ◽  
Amp Activated Protein Kinase

Abstract: Neurodegenerative disorders impact more than one billion individuals worldwide and are intimately tied to metabolic disease that can affect another nine hundred individuals throughput the globe. Nicotinamide is a critical agent that may offer fruitful prospects for neurodegenerative diseases and metabolic disorders, such as diabetes mellitus. Nicotinamide protects against multiple toxic environments that include reactive oxygen species exposure, anoxia, excitotoxicity, ethanolinduced neuronal injury, amyloid (Aß) toxicity, age-related vascular disease, mitochondrial dysfunction, insulin resistance, excess lactate production, and loss of glucose homeostasis with pancreatic β-cell dysfunction. However, nicotinamide offers cellular protection in a specific concentration range with dosing outside of this range leading to detrimental effects. The underlying biological pathways of nicotinamide that involve the silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), the mechanistic target of rapamycin (mTOR), AMP activated protein kinase (AMPK), and mammalian forkhead transcription factors (FoxOs) may offer insight for the clinical translation of nicotinamide into a safe and efficacious therapy through the modulation of oxidative stress, apoptosis, and autophagy. Nicotinamide is a highly promising target for the development of innovative strategies for neurodegenerative disorders and metabolic disease, but the fruits of this foundation depend greatly on gaining further understanding of nicotinamide’s complex biology.

scholarly journals ROS Defense Systems and Terminal Oxidases in Bacteria

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 839
Author(s):  
Vitaliy B. Borisov ◽  
Sergey A. Siletsky ◽  
Martina R. Nastasi ◽  
Elena Forte
Keyword(s):  
Defense Mechanisms ◽  
Protective Role ◽  
Superoxide Dismutases ◽  
Oxygen Species ◽  
Ros Scavenging ◽  
Terminal Oxidases ◽  
Defense Systems ◽  
Respiratory Chains ◽  
Scavenging Enzymes

Reactive oxygen species (ROS) comprise the superoxide anion (O2·−), hydrogen peroxide (H2O2), hydroxyl radical (·OH), and singlet oxygen (1O2). ROS can damage a variety of macromolecules, including DNA, RNA, proteins, and lipids, and compromise cell viability. To prevent or reduce ROS-induced oxidative stress, bacteria utilize different ROS defense mechanisms, of which ROS scavenging enzymes, such as superoxide dismutases, catalases, and peroxidases, are the best characterized. Recently, evidence has been accumulating that some of the terminal oxidases in bacterial respiratory chains may also play a protective role against ROS. The present review covers this role of terminal oxidases in light of recent findings.

scholarly journals Fighting Oxidative Stress with Sulfur: Hydrogen Sulfide in the Renal and Cardiovascular Systems

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 373
Author(s):  
Joshua J. Scammahorn ◽  
Isabel T. N. Nguyen ◽  
Eelke M. Bos ◽  
Harry Van Goor ◽  
Jaap A. Joles
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Sulfide ◽  
Redox Status ◽  
The Body ◽  
Therapeutic Interventions ◽  
Oxygen Species ◽  
Enzymatic Production ◽  
Age Related ◽  
Anti Oxidant ◽  
Enzymatic Pathways

Hydrogen sulfide (H2S) is an essential gaseous signaling molecule. Research on its role in physiological and pathophysiological processes has greatly expanded. Endogenous enzymatic production through the transsulfuration and cysteine catabolism pathways can occur in the kidneys and blood vessels. Furthermore, non-enzymatic pathways are present throughout the body. In the renal and cardiovascular system, H2S plays an important role in maintaining the redox status at safe levels by promoting scavenging of reactive oxygen species (ROS). H2S also modifies cysteine residues on key signaling molecules such as keap1/Nrf2, NFκB, and HIF-1α, thereby promoting anti-oxidant mechanisms. Depletion of H2S is implicated in many age-related and cardiorenal diseases, all having oxidative stress as a major contributor. Current research suggests potential for H2S-based therapies, however, therapeutic interventions have been limited to studies in animal models. Beyond H2S use as direct treatment, it could improve procedures such as transplantation, stem cell therapy, and the safety and efficacy of drugs including NSAIDs and ACE inhibitors. All in all, H2S is a prime subject for further research with potential for clinical use.

scholarly journals Nanoceria Prevents Glucose-Induced Protein Glycation in Eye Lens Cells

Nanomaterials ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1473
Author(s):  
Belal I. Hanafy ◽  
Gareth W. V. Cave ◽  
Yvonne Barnett ◽  
Barbara K. Pierscionek
Keyword(s):  
Protein Glycation ◽  
Human Lens ◽  
Lens Epithelial Cells ◽  
Oxide Nanoparticles ◽  
Lens Protein ◽  
Oxygen Species ◽  
Human Lens Epithelial Cells ◽  
Age Related ◽  
Age Related Changes

Cerium oxide nanoparticles (nanoceria) are generally known for their recyclable antioxidative properties making them an appealing biomaterial for protecting against physiological and pathological age-related changes that are caused by reactive oxygen species (ROS). Cataract is one such pathology that has been associated with oxidation and glycation of the lens proteins (crystallins) leading to aggregation and opacification. A novel coated nanoceria formulation has been previously shown to enter the human lens epithelial cells (HLECs) and protect them from oxidative stress induced by hydrogen peroxide (H2O2). In this work, the mechanism of nanoceria uptake in HLECs is studied and multiple anti-cataractogenic properties are assessed in vitro. Our results show that the nanoceria provide multiple beneficial actions to delay cataract progression by (1) acting as a catalase mimetic in cells with inhibited catalase, (2) improving reduced to oxidised glutathione ratio (GSH/GSSG) in HLECs, and (3) inhibiting the non-enzymatic glucose-induced glycation of the chaperone lens protein α-crystallin. Given the multifactorial nature of cataract progression, the varied actions of nanoceria render them promising candidates for potential non-surgical therapeutic treatment.

scholarly journals Combinatorial Therapeutic Effect of Inhibitors of Aldehyde Dehydrogenase and Mitochondrial Complex I, and the Chemotherapeutic Drug, Temozolomide against Glioblastoma Tumorspheres

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 282
Author(s):  
Hun Ho Park ◽  
Junseong Park ◽  
Hye Joung Cho ◽  
Jin-Kyoung Shim ◽  
Ju Hyung Moon ◽  
...  
Keyword(s):  
Aldehyde Dehydrogenase ◽  
Cell Metabolism ◽  
Dual Therapy ◽  
Mechanisms Of Action ◽  
Therapeutic Effects ◽  
Chemotherapeutic Drug ◽  
Mitochondrial Complex ◽  
Dual Inhibitors ◽  
Dual Inhibition ◽  
Tumor Bioenergetics

Resident cancer cells with stem cell-like features induce drug tolerance, facilitating survival of glioblastoma (GBM). We previously showed that strategies targeting tumor bioenergetics present a novel emerging avenue for treatment of GBM. The objective of this study was to enhance the therapeutic effects of dual inhibition of tumor bioenergetics by combination of gossypol, an aldehyde dehydrogenase inhibitor, and phenformin, a biguanide compound that depletes oxidative phosphorylation, with the chemotherapeutic drug, temozolomide (TMZ), to block proliferation, stemness, and invasiveness of GBM tumorspheres (TSs). Combination therapy with gossypol, phenformin, and TMZ induced a significant reduction in ATP levels, cell viability, stemness, and invasiveness compared to TMZ monotherapy and dual therapy with gossypol and phenformin. Analysis of differentially expressed genes revealed up-regulation of genes involved in programmed cell death, autophagy, and protein metabolism and down-regulation of those associated with cell metabolism, cycle, and adhesion. Combination of TMZ with dual inhibitors of tumor bioenergetics may, therefore, present an effective strategy against GBM by enhancing therapeutic effects through multiple mechanisms of action.

scholarly journals Age-Related Macular Degeneration: Role of Oxidative Stress and Blood Vessels

2021 ◽  
Vol 22 (3) ◽  
pp. 1296
Author(s):  
Yue Ruan ◽  
Subao Jiang ◽  
Adrian Gericke
Keyword(s):  
Oxidative Stress ◽  
Macular Degeneration ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Therapeutic Strategies ◽  
Vision Impairment ◽  
Age Related Macular Degeneration ◽  
Oxygen Species ◽  
Age Related

Age-related macular degeneration (AMD) is a common irreversible ocular disease characterized by vision impairment among older people. Many risk factors are related to AMD and interact with each other in its pathogenesis. Notably, oxidative stress and choroidal vascular dysfunction were suggested to be critically involved in AMD pathogenesis. In this review, we give an overview on the factors contributing to the pathophysiology of this multifactorial disease and discuss the role of reactive oxygen species and vascular function in more detail. Moreover, we give an overview on therapeutic strategies for patients suffering from AMD.

scholarly journals Differential regulation of AMP-activated protein kinase in healthy and cancer cells explains why V-ATPase inhibition selectively kills cancer cells

2019 ◽  
Vol 294 (46) ◽  
pp. 17239-17248
Author(s):  
Karin Bartel ◽  
Rolf Müller ◽  
Karin von Schwarzenberg
Keyword(s):  
Reactive Oxygen Species ◽  
Protein Kinase ◽  
Cancer Cells ◽  
Reactive Oxygen Species Production ◽  
Differential Regulation ◽  
Oxygen Species ◽  
Atpase Inhibitors ◽  
Species Production ◽  
Amp Activated Protein Kinase ◽  
Atpase Inhibition

The cellular energy sensor AMP-activated protein kinase (AMPK) is a metabolic hub regulating various pathways involved in tumor metabolism. Here we report that vacuolar H+-ATPase (V-ATPase) inhibition differentially affects regulation of AMPK in tumor and nontumor cells and that this differential regulation contributes to the selectivity of V-ATPase inhibitors for tumor cells. In nonmalignant cells, the V-ATPase inhibitor archazolid increased phosphorylation and lysosomal localization of AMPK. We noted that AMPK localization has a prosurvival role, as AMPK silencing decreased cellular growth rates. In contrast, in cancer cells, we found that AMPK is constitutively active and that archazolid does not affect its phosphorylation and localization. Moreover, V-ATPase–independent AMPK induction in tumor cells protected them from archazolid-induced cytotoxicity, further underlining the role of AMPK as a prosurvival mediator. These observations indicate that AMPK regulation is uncoupled from V-ATPase activity in cancer cells and that this makes them more susceptible to cell death induction by V-ATPase inhibitors. In both tumor and healthy cells, V-ATPase inhibition induced a distinct metabolic regulatory cascade downstream of AMPK, affecting ATP and NADPH levels, glucose uptake, and reactive oxygen species production. We could attribute the prosurvival effects to AMPK's ability to maintain redox homeostasis by inhibiting reactive oxygen species production and maintaining NADPH levels. In summary, the results of our work indicate that V-ATPase inhibition has differential effects on AMPK-mediated metabolic regulation in cancer and healthy cells and explain the tumor-specific cytotoxicity of V-ATPase inhibition.

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