scholarly journals Drosophila SLC22 Orthologs Related to OATs, OCTs, and OCTNs Regulate Development and Responsiveness to Oxidative Stress

2020 ◽  
Vol 21 (6) ◽  
pp. 2002 ◽  
Author(s):  
Darcy C. Engelhart ◽  
Priti Azad ◽  
Suwayda Ali ◽  
Jeffry C. Granados ◽  
Gabriel G. Haddad ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Drosophila Melanogaster ◽  
Organic Molecules ◽  
Fruit Fly ◽  
Evolutionary Analysis ◽  
Oxygen Species ◽  
Small Organic Molecules ◽  
Evolutionarily Conserved

The SLC22 family of transporters is widely expressed, evolutionarily conserved, and plays a major role in regulating homeostasis by transporting small organic molecules such as metabolites, signaling molecules, and antioxidants. Analysis of transporters in fruit flies provides a simple yet orthologous platform to study the endogenous function of drug transporters in vivo. Evolutionary analysis of Drosophila melanogaster putative SLC22 orthologs reveals that, while many of the 25 SLC22 fruit fly orthologs do not fall within previously established SLC22 subclades, at least four members appear orthologous to mammalian SLC22 members (SLC22A16:CG6356, SLC22A15:CG7458, CG7442 and SLC22A18:CG3168). We functionally evaluated the role of SLC22 transporters in Drosophila melanogaster by knocking down 14 of these genes. Three putative SLC22 ortholog knockdowns—CG3168, CG6356, and CG7442/SLC22A—did not undergo eclosion and were lethal at the pupa stage, indicating the developmental importance of these genes. Additionally, knocking down four SLC22 members increased resistance to oxidative stress via paraquat testing (CG4630: p < 0.05, CG6006: p < 0.05, CG6126: p < 0.01 and CG16727: p < 0.05). Consistent with recent evidence that SLC22 is central to a Remote Sensing and Signaling Network (RSSN) involved in signaling and metabolism, these phenotypes support a key role for SLC22 in handling reactive oxygen species.

scholarly journals FructationIn Vivo: Detrimental and Protective Effects of Fructose

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
H. M. Semchyshyn
Keyword(s):  
Oxidative Stress ◽  
Side Effects ◽  
Experimental Models ◽  
Oxygen Species ◽  
Protective Effects ◽  
Compelling Evidence ◽  
Animal Tissues

There is compelling evidence that long-term intake of excessive fructose can have deleterious side effects in different experimental models. However, the role of fructosein vivoremains controversial, since acute temporary application of fructose is found to protect yeast as well as animal tissues against exogenous oxidative stress. This review suggests the involvement of reactive carbonyl and oxygen species in both the cytotoxic and defensive effects of fructose. Potential mechanisms of the generation of reactive species by fructose in the nonenzymatic reactions, their implication in the detrimental and protective effects of fructose are discussed.

scholarly journals ROS in AgingCaenorhabditis elegans: Damage or Signaling?

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Patricia Back ◽  
Bart P. Braeckman ◽  
Filip Matthijssens
Keyword(s):  
Oxidative Stress ◽  
Aging Process ◽  
Model Organism ◽  
Mechanistic Explanation ◽  
Redox Status ◽  
Oxygen Species ◽  
C Elegans ◽  
Development And Aging

Many insights into the mechanisms and signaling pathways underlying aging have resulted from research on the nematodeCaenorhabditis elegans. In this paper, we discuss the recent findings that emerged using this model organism concerning the role of reactive oxygen species (ROS) in the aging process. The accrual of oxidative stress and damage has been the predominant mechanistic explanation for the process of aging for many years, but reviewing the recent studies inC. eleganscalls this theory into question. Thus, it becomes more and more evident that ROS are not merely toxic byproducts of the oxidative metabolism. Rather it seems more likely that tightly controlled concentrations of ROS and fluctuations in redox potential are important mediators of signaling processes. We therefore discuss some theories that explain how redox signaling may be involved in aging and provide some examples of ROS functions and signaling inC. elegansmetabolism. To understand the role of ROS and the redox status in physiology, stress response, development, and aging, there is a rising need for accurate and reversiblein vivodetection. Therefore, we comment on some methods of ROS and redox detection with emphasis on the implementation of genetically encoded biosensors inC. elegans.

scholarly journals Nutraceutical Strategy to Counteract Eye Neurodegeneration and Oxidative Stress in Drosophila melanogaster Fed with High-Sugar Diet

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1197
Author(s):  
Elisabetta Catalani ◽  
Giuseppina Fanelli ◽  
Federica Silvestri ◽  
Agnese Cherubini ◽  
Simona Del Quondam ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Drosophila Melanogaster ◽  
Antioxidant Properties ◽  
Fruit Fly ◽  
Retinal Cell ◽  
Food Supplementation ◽  
In Vivo Model ◽  
Retinal Neurons ◽  
High Sucrose

Aberrant production of reactive oxygen species (ROS) is a common feature of damaged retinal neurons in diabetic retinopathy, and antioxidants may exert both preventive and therapeutic action. To evaluate the beneficial and antioxidant properties of food supplementation with Lisosan G, a powder of bran and germ of grain (Triticum aestivum) obtained by fermentation with selected lactobacillus and natural yeast strains, we used an in vivo model of hyperglycemia-induced retinal damage, the fruit fly Drosophila melanogaster fed with high-sucrose diet. Lisosan G positively affected the visual system of hyperglycemic flies at structural/functional level, decreased apoptosis, and reactivated protective autophagy at the retina internal network. Also, in high sucrose-fed Drosophila, Lisosan G reduced the levels of brain ROS and retina peroxynitrite. The analysis of oxidative stress-related metabolites suggested 7,8-dihydrofolate, uric acid, dihydroorotate, γ-L-glutamyl-L-cysteine, allantoin, cysteinyl-glycine, and quinolate as key mediators of Lisosan G-induced inhibition of neuronal ROS, along with the upregulation of glutathione system. Of note, Lisosan G may impact oxidative stress and the ensuing retinal cell death, also independently from autophagy, although the autophagy-ROS cross-talk is critical. This study demonstrated that the continuous supplementation with the alimentary integrator Lisosan G exerts a robust and multifaceted antioxidant effect on retinal neurons, thus providing efficacious neuroprotection of hyperglycemic eye.

scholarly journals Efficient multiplexed genome engineering with a polycistronic tRNA and CRISPR guide-RNA reveals an important role of detonator in reproduction of Drosophila melanogaster

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0245454
Author(s):  
Cristin Chon ◽  
Grace Chon ◽  
Yurika Matsui ◽  
Huiqing Zeng ◽  
Zhi-Chun Lai ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Genome Engineering ◽  
Transmembrane Protein ◽  
Association Studies ◽  
Fruit Fly ◽  
Loss Of Function ◽  
Guide Rna ◽  
Genome Association

Genome association studies in human and genetic studies in mouse implicated members of the transmembrane protein 132 (TMEM132) family in multiple conditions including panic disorder, hearing loss, limb and kidney malformation. However, the presence of five TMEM132 paralogs in mammalian genomes makes it extremely challenging to reveal the full requirement for these proteins in vivo. In contrast, there is only one TMEM132 homolog, detonator (dtn), in the genome of fruit fly Drosophila melanogaster, enabling straightforward research into its in vivo function. In the current study, we generate multiple loss-of-function dtn mutant fly strains through a polycistronic tRNA-gRNA approach, and show that most embryos lacking both maternal and paternal dtn fail to hatch into larvae, indicating an essential role of dtn in Drosophila reproduction.

scholarly journals BRCA1 interacts with Nrf2 to regulate antioxidant signaling and cell survival

2013 ◽  
Vol 210 (8) ◽  
pp. 1529-1544 ◽  
Author(s):  
Chiara Gorrini ◽  
Pegah S. Baniasadi ◽  
Isaac S. Harris ◽  
Jennifer Silvester ◽  
Satoshi Inoue ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mammary Epithelial Cells ◽  
Antioxidant Response ◽  
Mammary Epithelial ◽  
Oxygen Species ◽  
Nrf2 Activation ◽  
The Impact ◽  
Low Expression

Oxidative stress plays an important role in cancer development and treatment. Recent data implicate the tumor suppressor BRCA1 in regulating oxidative stress, but the molecular mechanism and the impact in BRCA1-associated tumorigenesis remain unclear. Here, we show that BRCA1 regulates Nrf2-dependent antioxidant signaling by physically interacting with Nrf2 and promoting its stability and activation. BRCA1-deficient mouse primary mammary epithelial cells show low expression of Nrf2-regulated antioxidant enzymes and accumulate reactive oxygen species (ROS) that impair survival in vivo. Increased Nrf2 activation rescues survival and ROS levels in BRCA1-null cells. Interestingly, 53BP1 inactivation, which has been shown to alleviate several defects associated with BRCA1 loss, rescues survival of BRCA1-null cells without restoring ROS levels. We demonstrate that estrogen treatment partially restores Nrf2 levels in the absence of BRCA1. Our data suggest that Nrf2-regulated antioxidant response plays a crucial role in controlling survival downstream of BRCA1 loss. The ability of estrogen to induce Nrf2 posits an involvement of an estrogen-Nrf2 connection in BRCA1 tumor suppression. Lastly, BRCA1-mutated tumors retain a defective antioxidant response that increases the sensitivity to oxidative stress. In conclusion, the role of BRCA1 in regulating Nrf2 activity suggests important implications for both the etiology and treatment of BRCA1-related cancers.

Microbial Bioconversion: A Regio-specific Method for Novel Drug Design and Toxicological Study of Metabolites

2019 ◽  
Vol 20 (14) ◽  
pp. 1156-1162
Author(s):  
Maria Yousuf ◽  
Waqas Jamil ◽  
Khayala Mammadova
Keyword(s):  
Microbial Transformation ◽  
Specific Method ◽  
Reaction Conditions ◽  
Small Organic Molecules ◽  
Toxicological Studies ◽  
Drug Designing ◽  
Transformation Methods ◽  
Novel Drug

The methods of chemical structural alteration of small organic molecules by using microbes (fungi, bacteria, yeast, etc.) are gaining tremendous attention to obtain structurally novel and therapeutically potential leads. The regiospecific mild environmental friendly reaction conditions with the ability of novel chemical structural modification in compounds categorize this technique; a distinguished and unique way to obtain medicinally important drugs and their in vivo mimic metabolites with costeffective and timely manner. This review article shortly addresses the immense pharmaceutical importance of microbial transformation methods in drug designing and development as well as the role of CYP450 enzymes in fungi to obtain in vivo drug metabolites for toxicological studies.

scholarly journals Targeting Autophagy to Counteract Obesity-Associated Oxidative Stress

Antioxidants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 102
Author(s):  
Federico Pietrocola ◽  
José Manuel Bravo-San Pedro
Keyword(s):  
Oxidative Stress ◽  
Oxygen Species ◽  
Alcoholic Fatty Liver ◽  
Redox Biology ◽  
Obesity Therapy ◽  
Treatment Of Obesity ◽  
Novel Therapeutic Strategies ◽  
Alcoholic Fatty Liver Disease ◽  
Shed Light

Reactive oxygen species (ROS) operate as key regulators of cellular homeostasis within a physiological range of concentrations, yet they turn into cytotoxic entities when their levels exceed a threshold limit. Accordingly, ROS are an important etiological cue for obesity, which in turn represents a major risk factor for multiple diseases, including diabetes, cardiovascular disorders, non-alcoholic fatty liver disease, and cancer. Therefore, the implementation of novel therapeutic strategies to improve the obese phenotype by targeting oxidative stress is of great interest for the scientific community. To this end, it is of high importance to shed light on the mechanisms through which cells curtail ROS production or limit their toxic effects, in order to harness them in anti-obesity therapy. In this review, we specifically discuss the role of autophagy in redox biology, focusing on its implication in the pathogenesis of obesity. Because autophagy is specifically triggered in response to redox imbalance as a quintessential cytoprotective mechanism, maneuvers based on the activation of autophagy hold promises of efficacy for the prevention and treatment of obesity and obesity-related morbidities.

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 Mitochondrion-Dependent Cell Death in TDP-43 Proteinopathies

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 376
Author(s):  
Chantal B. Lucini ◽  
Ralf J. Braun
Keyword(s):  
Cell Death ◽  
Oxygen Species ◽  
In Vivo Models ◽  
Dependent Cell ◽  
Cell Death Mechanisms ◽  
Sting Pathway ◽  
Mitochondrial Membrane Permeabilization

In the last decade, pieces of evidence for TDP-43-mediated mitochondrial dysfunction in neurodegenerative diseases have accumulated. In patient samples, in vitro and in vivo models have shown mitochondrial accumulation of TDP-43, concomitantly with hallmarks of mitochondrial destabilization, such as increased production of reactive oxygen species (ROS), reduced level of oxidative phosphorylation (OXPHOS), and mitochondrial membrane permeabilization. Incidences of TDP-43-dependent cell death, which depends on mitochondrial DNA (mtDNA) content, is increased upon ageing. However, the molecular pathways behind mitochondrion-dependent cell death in TDP-43 proteinopathies remained unclear. In this review, we discuss the role of TDP-43 in mitochondria, as well as in mitochondrion-dependent cell death. This review includes the recent discovery of the TDP-43-dependent activation of the innate immunity cyclic GMP-AMP synthase/stimulator of interferon genes (cGAS/STING) pathway. Unravelling cell death mechanisms upon TDP-43 accumulation in mitochondria may open up new opportunities in TDP-43 proteinopathy research.

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