Aging reduces responsiveness to BSO- and heat stress-induced perturbations of glutathione and antioxidant enzymes

2005 ◽  
Vol 289 (4) ◽  
pp. R1035-R1041 ◽  
Author(s):  
Joanna P. Morrison ◽  
Mitchell C. Coleman ◽  
Elizabeth S. Aunan ◽  
Susan A. Walsh ◽  
Douglas R. Spitz ◽  
...  
Keyword(s):  
Antioxidant Enzymes ◽  
Heat Stress ◽  
Redox Homeostasis ◽  
Buthionine Sulfoximine ◽  
Sod Activity ◽  
Glutamate Cysteine Ligase ◽  
Age Related ◽  
Rate Limiting ◽  
And Oxidative Stress

Aging alters cellular responses to both heat and oxidative stress. Thiol-mediated metabolism of reactive oxygen species (ROS) is believed to be important in aging. To begin to determine the role of thiols in aging and heat stress, we depleted liver glutathione (GSH) by administering l-buthionine sulfoximine (BSO) in young (6 mo) and old (24 mo) Fisher 344 rats before heat stress. Animals were given BSO (4 mmol/kg ip) or saline (1 ml ip) 2 h before heat stress and subsequently heated to a core temperature of 41°C over a 90-min period. Liver tissue was collected before and 0, 30, and 60 min after heat stress. BSO inhibited glutamate cysteine ligase (GCL, the rate-limiting enzyme in GSH synthesis) catalytic activity and resulted in a decline in liver GSH and GSSG that was more pronounced in young compared with old animals. Catalase activity did not change between groups until 60 min after heat stress in young BSO-treated rats. Young animals experienced a substantial and persistent reduction in Cu,Zn-SOD activity with BSO treatment. Mn-SOD activity increased with BSO but declined after heat stress. The differences in thiol depletion observed between young and old animals with BSO treatment may be indicative of age-related differences in GSH compartmentalization that could have an impact on maintenance of redox homeostasis and antioxidant balance immediately after a physiologically relevant stress. The significant changes in antioxidant enzyme activity after GSH depletion suggest that thiol status can influence the regulation of other antioxidant enzymes.

Involvement of Heme Oxygenase-1 in Neuropsychiatric and Neurodegenerative Diseases

2018 ◽  
Vol 24 (20) ◽  
pp. 2283-2302 ◽  
Author(s):  
Vivian B. Neis ◽  
Priscila B. Rosa ◽  
Morgana Moretti ◽  
Ana Lucia S. Rodrigues
Keyword(s):  
Neurodegenerative Diseases ◽  
Heme Oxygenase ◽  
Therapeutic Potential ◽  
Redox Homeostasis ◽  
Antioxidant Defenses ◽  
Heme Oxygenase 1 ◽  
Physiological Conditions ◽  
And Oxidative Stress ◽  
Defensive Mechanism

Heme oxygenase (HO) family catalyzes the conversion of heme into free iron, carbon monoxide and biliverdin. It possesses two well-characterized isoforms: HO-1 and HO-2. Under brain physiological conditions, the expression of HO-2 is constitutive, abundant and ubiquitous, whereas HO-1 mRNA and protein are restricted to small populations of neurons and neuroglia. HO-1 is an inducible enzyme that has been shown to participate as an essential defensive mechanism for neurons exposed to oxidant challenges, being related to antioxidant defenses in certain neuropathological conditions. Considering that neurodegenerative diseases (Alzheimer’s Disease (AD), Parkinson’s Disease (PD) and Multiple Sclerosis (MS)) and neuropsychiatric disorders (depression, anxiety, Bipolar Disorder (BD) and schizophrenia) are associated with increased inflammatory markers, impaired redox homeostasis and oxidative stress, conditions that may be associated with alterations in HO-levels/activity, the purpose of this review is to present evidence on the possible role of HO-1 in these Central Nervous System (CNS) diseases. In addition, the possible therapeutic potential of targeting brain HO-1 is explored in this review.

scholarly journals P0981ANTIDIABETIC AND RENOPROTECTIVE ROLE OF METFORMIN ON METABOLIC PARAMETERS IN KIDNEY OF DIABETIC AGING RATS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Pardeep Kumar ◽  
Najma Baquer
Keyword(s):  
Renal Function ◽  
Antioxidant Enzymes ◽  
Membrane Fluidity ◽  
Renin Angiotensin System ◽  
Glucose Transporters ◽  
Dna Degradation ◽  
Female Rats ◽  
Aging Rats ◽  
Age Related

Abstract Background and Aims The objective of this study was to investigate renoprotective effects of metformin on renal function, mitochondrial and antioxidant enzymes, oxidative stress biomarker, DNA degradation and expression of glucose transporters in of diabetic aging female rats. Method Young (3 months) adult (12 months) and aged (24 months) rats will be diabetic by using alloxan monohydrate. Metformin was administered i.p. at a dose of 200 mg/kg/day for 30 days to both control and diabetic aging rats. A detailed study was carried on membrane fluidity, lipofuscin, antioxidant enzymes and DNA degradation to identify the antidiabetic and antiaging role of metformin using biochemical ,molecular and histiochemical study. Renal function was assessed by measuring proteinuria, enzymuria, expression of glucose transporters, renin-angiotensin system, and activities of polyol pathway enzymes. Results Present study shows that there was a similar pattern of increased lipid peroxidation, lipofuscin, DNA degradation and glucose transporters expression with upregulation of renal angiotensin-converting enzyme and a decrease in membrane fluidity, glutamate dehydrogenase, Na+ K+ ATPse, antixodant enzymes activities in both aging and diabetes. Metformin treatment helped to reverse the age related changes studied, to normal levels, elucidating an anti-aging, antidiabetic and renoprotective action. Metformin effectively countered the diabetes-induced structural abnormalities of renal tissue of aging rats. Conclusion Metformin was found to be an effective treatment in stabilizing and normalizing the renal functions; therefore this therapy can be considered an alternative to be explored further as a means of diabetic and aged related disorders control. The results of this study will be useful for pharmacological modification of the aging process and applying new strategies for control of age related disorders including metabolic syndrome.

scholarly journals The Role of Free Radicals in Autophagy Regulation: Implications for Ageing

2018 ◽  
Vol 2018 ◽  
pp. 1-19 ◽  
Author(s):  
M. Pajares ◽  
A. Cuadrado ◽  
N. Engedal ◽  
Z. Jirsova ◽  
M. Cahova
Keyword(s):  
Control Systems ◽  
Redox Homeostasis ◽  
Biological Macromolecules ◽  
Complex Relationship ◽  
Cellular Functions ◽  
Related Disorder ◽  
Redox Signalling ◽  
Age Related ◽  
Integral Role

Reactive oxygen and nitrogen species (ROS and RNS, resp.) have been traditionally perceived solely as detrimental, leading to oxidative damage of biological macromolecules and organelles, cellular demise, and ageing. However, recent data suggest that ROS/RNS also plays an integral role in intracellular signalling and redox homeostasis (redoxtasis), which are necessary for the maintenance of cellular functions. There is a complex relationship between cellular ROS/RNS content and autophagy, which represents one of the major quality control systems in the cell. In this review, we focus on redox signalling and autophagy regulation with a special interest on ageing-associated changes. In the last section, we describe the role of autophagy and redox signalling in the context of Alzheimer’s disease as an example of a prevalent age-related disorder.

scholarly journals ROLE OF INSULIN IN BRAIN: DELVE INTO THE MOLECULAR MECHANISMS

2021 ◽  
Author(s):  
Sofia Khanam
Keyword(s):  
Molecular Mechanisms ◽  
Insulin Signalling ◽  
Diabetic Patients ◽  
Functional Activities ◽  
Mitochondrial Alterations ◽  
Age Related ◽  
The Brain ◽  
And Oxidative Stress

We have learned over the last several decades that the brain is an important target for insulin action. In central nervous system (CNS) it mainly affects feeding behaviour and various aspects of memory and cognition. Insulin signalling in CNS has emerged as a novel field of research since decreases brain insulin levels and signalling were associated to impaired learning, memory and age-related neurodegenerative diseases. Alterations of these functional activities may contribute to the manifestation of several clinical entities, such as central insulin resistance, type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD). A close alliance between T2DM and AD has been reported, to the extent that AD is twice more frequent in diabetic patients. There are links between T2DM and AD through mitochondrial alterations and oxidative stress, altered energy and glucose metabolism, cholesterol modifications, dysfunctional protein O-GlcNAcylation, formation of amyloid plaques, altered Aβ metabolism and tau hyperphosphorylation. Herewith, we aim to integrate the metabolic, neuromodulatory, and neuroprotective roles of insulin in two age-related pathologies: T2DM and AD, both in terms of intracellular signalling and potential therapeutic approach.

scholarly journals Hydrostatic Pressure Regulates Oxidative Stress through microRNA in Human Osteoarthritic Chondrocytes

2020 ◽  
Vol 21 (10) ◽  
pp. 3653
Author(s):  
Sara Cheleschi ◽  
Marcella Barbarino ◽  
Ines Gallo ◽  
Sara Tenti ◽  
Maria Bottaro ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Hydrostatic Pressure ◽  
B Cell Lymphoma ◽  
Type Ii Collagen ◽  
Mrna Levels ◽  
Osteoarthritic Chondrocytes ◽  
The Relationship ◽  
And Oxidative Stress

Hydrostatic pressure (HP) modulates chondrocytes metabolism, however, its ability to regulate oxidative stress and microRNAs (miRNA) has not been clarified. The aim of this study was to investigate the role of miR-34a, miR-146a, and miR-181a as possible mediators of HP effects on oxidative stress in human osteoarthritis (OA) chondrocytes. Chondrocytes were exposed to cyclic low HP (1–5 MPa) and continuous static HP (10 MPa) for 3~h. Metalloproteinases (MMPs), disintegrin and metalloproteinase with thrombospondin motif (ADAMTS)-5, type II collagen (Col2a1), miR-34a, miR-146a, miR-181a, antioxidant enzymes, and B-cell lymphoma 2 (BCL2) were evaluated by quantitative real-time polymerase chain reaction qRT-PCR, apoptosis and reactive oxygen species ROS production by cytometry, and β-catenin by immunofluorescence. The relationship among HP, the studied miRNA, and oxidative stress was assessed by transfection with miRNA specific inhibitors. Low cyclical HP significantly reduced apoptosis, the gene expression of MMP-13, ADAMTS5, miRNA, the production of superoxide anion, and mRNA levels of antioxidant enzymes. Conversely, an increased Col2a1 and BCL2 genes was observed. β-catenin protein expression was reduced in cells exposed to HP 1–5 MPa. Opposite results were obtained following continuous static HP application. Finally, miRNA silencing enhanced low HP and suppressed continuous HP-induced effects. Our data suggest miRNA as one of the mechanisms by which HP regulates chondrocyte metabolism and oxidative stress, via Wnt/β-catenin pathway.

scholarly journals New Insights in the Pathogenesis of HPV Infection and the Associated Carcinogenic Processes: The Role of Chronic Inflammation and Oxidative Stress

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Simona Roxana Georgescu ◽  
Cristina Iulia Mitran ◽  
Madalina Irina Mitran ◽  
Constantin Caruntu ◽  
Maria Isabela Sarbu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Inflammation ◽  
Cell Damage ◽  
Redox Homeostasis ◽  
Harmful Effect ◽  
Hpv Infection ◽  
Host Cells ◽  
E6 And E7 ◽  
And Oxidative Stress

Human papillomavirus (HPV) is a small double-stranded DNA virus with tropism for epithelial cells. To this date, over 150 genotypes are known and are classified into two major groups, low-risk and high-risk strains, depending on the ability of the virus to induce malignant transformation. The host’s immunity plays a central role in the course of the infection; therefore, it may not be clinically manifest or may produce various benign or malignant lesions. The pathogenic mechanisms are complex and incompletely elucidated. Recent research suggests the role of chronic inflammation and oxidative stress (OS) in the pathogenesis of HPV infection and the associated carcinogenic processes. Chronic inflammation induces OS, which in turn promotes the perpetuation of the inflammatory process resulting in the release of numerous molecules which cause cell damage. Reactive oxygen species exert a harmful effect on proteins, lipids, and nucleic acids. Viral oncogenes E5, E6, and E7 are involved in the development of chronic inflammation through various mechanisms. In addition, HPV may interfere with redox homeostasis of host cells, inducing OS which may be involved in the persistence of the infection and play a certain role in viral integration and promotion of carcinogenesis. Knowledge regarding the interplay between chronic inflammation and OS in the pathogenesis of HPV infection and HPV-induced carcinogenesis has important consequences on the development of new therapeutic strategies.

scholarly journals The Amelioration of N-Acetyl-p-Benzoquinone Imine Toxicity by Ginsenoside Rg3: The Role of Nrf2-Mediated Detoxification and Mrp1/Mrp3 Transports

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Sang Il Gum ◽  
Min Kyung Cho
Keyword(s):  
Mrna Levels ◽  
Ginsenoside Rg3 ◽  
Korean Red Ginseng ◽  
Metabolic Intermediate ◽  
Glutamate Cysteine Ligase ◽  
Benzoquinone Imine ◽  
H4iie Cells ◽  
Rate Limiting ◽  
Gene Regulations

Previously, we found that Korean red ginseng suppressed acetaminophen (APAP)-induced hepatotoxicity via alteration of its metabolic profile involving GSTA2 induction and that ginsenoside Rg3 was a major component of this gene induction. In the present study, therefore, we assessed the protective effect of Rg3 against N-acetyl-p-benzoquinone imine (NAPQI), a toxic metabolic intermediate of APAP. Excess NAPQI resulted in GSH depletion with increases in the ALT and AST activities in H4IIE cells. Rg3 pretreatment reversed GSH depletion by NAPQI. Rg3 resulted in increased mRNA levels of the catalytic and modulatory subunit of glutamate cysteine ligase (GCL), the rate-limiting steps in GSH synthesis and subsequently increased GSH content. Rg3 increased levels of nuclear Nrf2, an essential transcriptional factor of these genes. The knockdown or knockout of the Nrf2 gene abrogated the inductions of mRNA and protein by Rg3. Abolishment of the reversal of GSH depletion by Rg3 against NAPQI was observed in Nrf2-deficient cells. Rg3 induced multidrug resistance-associated protein (Mrp) 1 and Mrp3 mRNA levels, but not in Nrf2-deficient cells. Taken together, these results demonstrate that Rg3 is efficacious in protecting hepatocytes against NAPQI insult, due to GSH repletion and coordinated gene regulations of GSH synthesis and Mrp family genes by Nrf2.

Sign in / Sign up

Export Citation Format

Share Document