scholarly journals Kluyveromyces lactis: A Suitable Yeast Model to Study Cellular Defense Mechanisms against Hypoxia-Induced Oxidative Stress

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
M. Isabel González Siso ◽  
M. Esperanza Cerdán
Keyword(s):  
Oxidative Stress ◽  
Defense Mechanisms ◽  
Molecular Mechanisms ◽  
Kluyveromyces Lactis ◽  
Oxidative Stress Response ◽  
Unicellular Eukaryote ◽  
Extended Model ◽  
Cellular Defense ◽  
Health Disorders ◽  
Fermentative Yeast

Studies about hypoxia-induced oxidative stress in human health disorders take advantage from the use of unicellular eukaryote models. A widely extended model is the fermentative yeastSaccharomyces cerevisiae. In this paper, we describe an overview of the molecular mechanisms induced by a decrease in oxygen availability and their interrelationship with the oxidative stress response in yeast. We focus on the differential characteristics betweenS. cerevisiaeand the respiratory yeastKluyveromyces lactis, a complementary emerging model, in reference to multicellular eukaryotes.

The role of corneal crystallins in the cellular defense mechanisms against oxidative stress

2008 ◽  
Vol 19 (2) ◽  
pp. 100-112 ◽  
Author(s):  
Natalie Lassen ◽  
William J. Black ◽  
Tia Estey ◽  
Vasilis Vasiliou
Keyword(s):  
Oxidative Stress ◽  
Defense Mechanisms ◽  
Cellular Defense

scholarly journals Functional crosstalk between myeloid Foxo1–β-catenin axis and Hedgehog/Gli1 signaling in oxidative stress response

2020 ◽  
Author(s):  
Changyong Li ◽  
Mingwei Sheng ◽  
Yuanbang Lin ◽  
Dongwei Xu ◽  
Yizhu Tian ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Cell Metabolism ◽  
Ischemia Reperfusion ◽  
Neutrophil Infiltration ◽  
Oxidative Stress Response ◽  
Proinflammatory Mediators ◽  
Hepatocellular Damage

AbstractFoxo1 transcription factor is an evolutionarily conserved regulator of cell metabolism, oxidative stress, inflammation, and apoptosis. Activation of Hedgehog/Gli signaling is known to regulate cell growth, differentiation, and immune function. However, the molecular mechanisms by which interactive cell signaling networks restrain oxidative stress response and necroptosis are still poorly understood. Here, we report that myeloid-specific Foxo1 knockout (Foxo1M-KO) mice were resistant to oxidative stress-induced hepatocellular damage with reduced macrophage/neutrophil infiltration, and proinflammatory mediators in liver ischemia/reperfusion injury (IRI). Foxo1M-KO enhanced β-catenin-mediated Gli1/Snail activity, and reduced receptor-interacting protein kinase 3 (RIPK3) and NIMA-related kinase 7 (NEK7)/NLRP3 expression in IR-stressed livers. Disruption of Gli1 in Foxo1M-KO livers deteriorated liver function, diminished Snail, and augmented RIPK3 and NEK7/NLRP3. Mechanistically, macrophage Foxo1 and β-catenin colocalized in the nucleus, whereby the Foxo1 competed with T-cell factor (TCF) for interaction with β-catenin under inflammatory conditions. Disruption of the Foxo1–β-catenin axis by Foxo1 deletion enhanced β-catenin/TCF binding, activated Gli1/Snail signaling, leading to inhibited RIPK3 and NEK7/NLRP3. Furthermore, macrophage Gli1 or Snail knockout activated RIPK3 and increased hepatocyte necroptosis, while macrophage RIPK3 ablation diminished NEK7/NLRP3-driven inflammatory response. Our findings underscore a novel molecular mechanism of the myeloid Foxo1–β-catenin axis in regulating Hedgehog/Gli1 function that is key in oxidative stress-induced liver inflammation and necroptosis.

scholarly journals Antioxidants: Pharmacothearapeutic Boon for Diabetes

2021 ◽  
Author(s):  
Varuna Suresh ◽  
Amala Reddy ◽  
Pavithra Muthukumar ◽  
Thendarl Selvam
Keyword(s):  
Oxidative Stress ◽  
Defense Mechanisms ◽  
Cellular Response ◽  
Cell Function ◽  
Glucose Variability ◽  
Diabetic Rats ◽  
Long Term Effects ◽  
Free Radical Damage ◽  
Cellular Defense ◽  
Elevated Glucose

Glucose-induced oxidative stress can be found related to “glucose variability” and “glucose memory”. The irregular low and elevated glucose conditions cause damage to endothelial cell function than a steady, constant rise in level of glucose. Activation of PKC, NADPH oxidases, and mitochondrial oxidants are some of the pathways exhibited as a result of this aggravated cellular response. Regarding glucose memory, long after the normalization elevated level of glucose in the endothelial cells of diabetic rats and culture, a existance or ‘memory’ of induced basement membrane mRNA is expressed. This demonstrates that glucose causes dangerous long-term effects beyond the hyperglycemia period. Oxidative stress give rise to glucotoxicity and lipotoxicity which are phenomena’s related to diabetes. Following the pathogenesis of diabetes, hyperglycemia and hyperlipidemia exerts a supplementary toxic effect on the beta-cells. So, hyperglycemia can be considered as a requirement for the destructive effects of lipotoxicity. Thus glucolipotoxicity can be considered as a substitute for lipotoxicity which relates the detrimental correlation between lipids and beta-cell function. Generally, the antioxidant pharmacotherapy can be coupled with drugs to boost the natural cellular defense mechanisms as the naturally existing antioxidant components, which neutralizes free radical damage. This considers antioxidant a boon tool for pharmacotherapeutic agent.

scholarly journals Discovery of a Highly Selective MC1R Agonists Pentapeptide to Be Used as a Skin Pigmentation Enhancer and with Potential Anti-Aging Properties

2019 ◽  
Vol 20 (24) ◽  
pp. 6143 ◽  
Author(s):  
Eileen Jackson ◽  
Marc Heidl ◽  
Dominik Imfeld ◽  
Laurent Meeus ◽  
Rolf Schuetz ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Defense Mechanisms ◽  
Ex Vivo ◽  
Skin Pigmentation ◽  
Oxidative Stress Response ◽  
Melanocortin 1 Receptor ◽  
Melanocyte Stimulating Hormone ◽  
Uva Irradiation

One of the first lines of cutaneous defense against photoaging is (a) the synthesis of melanin and (b) the initiation of an oxidative stress response to protect skin against the harmful effects of solar radiation. Safe and selective means to stimulate epidermal pigmentation associated with oxidative stress defense are; however, scarce. Activation of the melanocortin-1 receptor (MC1R) on epidermal melanocytes represents a key step in cutaneous pigmentation initiation and, additionally, it regulates cellular defense mechanisms like oxidative stress and DNA-repair. Thus, making the activation of MC1R an attractive strategy for modulating skin pigmentation and oxidative stress. In this context, we designed and synthesized pentapeptides that act as MC1R agonists. These peptides bound, with high potency, to MC1R and activated cAMP synthesis in CHO cells expressing human MC1R. Using one lead pentapeptide, we could show that this activation of MC1R was specific as testing the activation of other G-protein coupled receptors, including the MC-receptor family, was negative. In vitro efficacy on mouse melanoma cells showed similar potency as for the synthetic MC1R agonist alpha-melanocyte stimulating hormone (NDP-alpha-MSH). Moreover, we could reproduce this activity in human skin tissue culture. The lead pentapeptide was able to induce ex-vivo protein expression of key melanogenesis markers melanocyte inducing transcription factor (MITF), tyrosinase (TYR), and tyrosinase-related protein 1 (TYRP-1). Concerning oxidative stress response, we found that the pentapeptide enhanced the activation of Nrf2 after UVA-irradiation. Our results make this pentapeptide an ideal candidate as a skin pigmentation enhancer that mimics alpha-MSH and may also have anti-photoaging effects on the skin.

scholarly journals 4-PHENYLBUTYRATE: MOLECULAR MECHANISMS AND AGING INTERVENTION POTENTIAL

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S101-S101
Author(s):  
Michael R Bene ◽  
Kevin Thyne ◽  
Jonathan Dorigatti ◽  
Adam B Salmon
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Molecular Mechanisms ◽  
Oxidative Stress Response ◽  
Chemical Chaperone ◽  
Mouse Muscle ◽  
Age Related ◽  
Primary Mouse ◽  
Wide Range

Abstract 4-Phenylbutyrate (PBA) is a FDA approved drug for treating patients with urea cycle disorders. Additionally, PBA acts upon several pathways thought of as important modifiers of aging including: histone deacetylation, proteostasis as a chemical chaperone, and stress resistance by regulating expression of oxidative stress response proteins. PBA has also been shown to extend lifespan and improve markers of age-related health in Drosophila. Due to its wide range of effects PBA has been investigated for use in numerous age-related disorders including neurodegenerative and cardiovascular diseases. To better understand the effects of PBA on the molecular level, we used both in cellulo and in vivo studies. Treatment of primary mouse fibroblasts, C2C12 mouse muscle cells, and NCTC 1469 mouse liver cells with PBA demonstrated differential responses among cell lines to upregulation of oxidative stress response and histone acetylation. Specifically, upregulation of the oxidative stress response protein DJ-1 by PBA was found to have a corresponding dose response curve to histone H3 acetylation in primary fibroblasts. To study effects of PBA in vivo, four cohorts of HET3 mice were treated with PBA at different doses in drinking water for 4 weeks. PBA was well tolerated and led to different effects on body composition dependent on the sex of mice. We are currently investigating the molecular effects of PBA treatment in multiple tissues samples from these mice. The potential of PBA to alter many fundamental pathways, and specifically those related to stress responses, make it an attractive prospect for treatment of many age-related disorders.

scholarly journals p62/SQSTM1-droplet serves as a platform for autophagosome formation and anti-oxidative stress response

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shun Kageyama ◽  
Sigurdur Runar Gudmundsson ◽  
Yu-Shin Sou ◽  
Yoshinobu Ichimura ◽  
Naoki Tamura ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Oxidative Stress Response ◽  
Liquid Droplets ◽  
Autophagosome Formation ◽  
Selective Autophagy ◽  
Selective Degradation ◽  
Physiological Relevance ◽  
Related Proteins

AbstractAutophagy contributes to the selective degradation of liquid droplets, including the P-Granule, Ape1-complex and p62/SQSTM1-body, although the molecular mechanisms and physiological relevance of selective degradation remain unclear. In this report, we describe the properties of endogenous p62-bodies, the effect of autophagosome biogenesis on these bodies, and the in vivo significance of their turnover. p62-bodies are low-liquidity gels containing ubiquitin and core autophagy-related proteins. Multiple autophagosomes form on the p62-gels, and the interaction of autophagosome-localizing Atg8-proteins with p62 directs autophagosome formation toward the p62-gel. Keap1 also reversibly translocates to the p62-gels in a p62-binding dependent fashion to activate the transcription factor Nrf2. Mice deficient for Atg8-interaction-dependent selective autophagy show that impaired turnover of p62-gels leads to Nrf2 hyperactivation in vivo. These results indicate that p62-gels are not simple substrates for autophagy but serve as platforms for both autophagosome formation and anti-oxidative stress.

scholarly journals Molecular Responses of Lactobacilli to Plant Phenolic Compounds: A Comparative Review of the Mechanisms Involved

Antioxidants ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 18
Author(s):  
Félix López de Felipe ◽  
Blanca de las Rivas ◽  
Rosario Muñoz
Keyword(s):  
Oxidative Stress ◽  
Phenolic Compounds ◽  
Molecular Mechanisms ◽  
Antimicrobial Agents ◽  
Oxidative Stress Response ◽  
Molecular Responses ◽  
Selective Pressures ◽  
Comparative Review ◽  
Bacterial Groups ◽  
Lactobacillus Spp

Lactobacilli are well-studied bacteria that can undergo oxidative selective pressures by plant phenolic compounds (PPCs) in plants, during some food fermentations or in the gastrointestinal tract of animals via dietary inputs. Lactobacilli are known to be more tolerant to PPCs than other bacterial groups and, therefore, must have mechanisms to cope with the effects of these metabolites. In this review, we intend to present what is currently known about the basics beyond the responses of Lactobacillus spp. to individual PPCs. We review the molecular mechanisms that are engaged in the PPC-modulated responses studied to date in these bacteria that have been mainly characterized by system-based strategies, and we discuss their differences and similarities. A wide variety of mechanisms are induced to increase the oxidative stress response highlighting the antimicrobial nature of PPCs. However other uncovered mechanisms that are involved in the response to these compounds are reviewed, including the capacity of PPCs to modulate the expression of molecular functions used by lactobacilli to adapt to host environments. This shows that these phytochemicals can act as more than just antimicrobial agents in the dual interaction with lactobacilli.

scholarly journals TXNIP Links Innate Host Defense Mechanisms to Oxidative Stress and Inflammation in Retinal Muller Glia under Chronic Hyperglycemia: Implications for Diabetic Retinopathy

2012 ◽  
Vol 2012 ◽  
pp. 1-19 ◽  
Author(s):  
Takhellambam S. Devi ◽  
Icksoo Lee ◽  
Maik Hüttemann ◽  
Ashok Kumar ◽  
Kwaku D. Nantwi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Retinopathy ◽  
Er Stress ◽  
Host Defense ◽  
Defense Mechanisms ◽  
Immune Response Gene ◽  
Ros Generation ◽  
Muller Glia ◽  
Müller Glia ◽  
Cellular Defense

Thioredoxin Interacting Protein (TXNIP) mediates retinal inflammation, gliosis, and apoptosis in experimental diabetes. Here, we investigate the temporal response of Muller glia to high glucose (HG) and TXNIP expression using a rat Muller cell line (rMC1) in culture. We examined if HG-induced TXNIP expression evokes host defense mechanisms in rMC1 in response to metabolic abnormalities. HG causes sustained up-regulation of TXNIP (2 h to 5 days), ROS generation, ATP depletion, ER stress, and inflammation. Various cellular defense mechanisms are activated by HG: (i) NLRP3 inflammasome, (ii) ER stress response (sXBP1), (iii) hypoxic-like HIF-1αinduction, (iv) autophagy/mitophagy, and (v) apoptosis. We also foundin vivothat streptozocin-induced diabetic rats have higher retinal TXNIP and innate immune response gene expression than normal rats. Knock down of TXNIP by intravitreal siRNA reduces inflammation (IL-1β) and gliosis (GFAP) in the diabetic retina. TXNIP ablationin vitroprevents ROS generation, restores ATP level and autophagic LC3B induction in rMC1. Thus, our results show that HG sustains TXNIP up-regulation in Muller glia and evokes a program of cellular defense/survival mechanisms that ultimately lead to oxidative stress, ER stress/inflammation, autophagy and apoptosis. TXNIP is a potential target to ameliorate blinding ocular complications of diabetic retinopathy.

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