scholarly journals Cyclin A2 promotes DNA repair in the brain during both development and aging

Aging ◽  
2016 ◽  
Vol 8 (7) ◽  
pp. 1540-1570 ◽  
Author(s):  
Patrick E. Gygli ◽  
Joshua C. Chang ◽  
Hamza N. Gokozan ◽  
Fay P. Catacutan ◽  
Theresa A. Schmidt ◽  
...  
Keyword(s):  
Dna Repair ◽  
Cyclin A2 ◽  
Development And Aging ◽  
The Brain

scholarly journals Endogenous formaldehyde scavenges cellular glutathione resulting in cytotoxic redox disruption

2020 ◽  
Author(s):  
Carla Umansky ◽  
Agustín Morellato ◽  
Marco Scheidegger ◽  
Matthias Rieckher ◽  
Manuela R. Martinefski ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Repair ◽  
Fanconi Anemia ◽  
Redox Homeostasis ◽  
Thiol Group ◽  
Cellular Damage ◽  
Repair Pathway ◽  
Cellular Redox ◽  
Redox Active ◽  
Development And Aging

AbstractFormaldehyde (FA) is a ubiquitous endogenous and environmental metabolite that is thought to exert cytotoxicity through DNA and DNA-protein crosslinking. We show here that FA can cause cellular damage beyond genotoxicity by triggering oxidative stress, which is prevented by the enzyme alcohol dehydrogenase 5 (ADH5/GSNOR). Mechanistically, we determine that endogenous FA reacts with the redox-active thiol group of glutathione (GSH) forming S-hydroxymethyl-GSH, which is metabolized by ADH5 yielding reduced GSH thus preventing redox disruption. We identify the ADH5-ortholog gene in Caenorhabditis elegans and show that oxidative stress also underlies FA toxicity in nematodes. Moreover, we show that endogenous GSH can protect cells lacking the Fanconi Anemia DNA repair pathway from FA, which might have broad implications for Fanconi Anemia patients and for healthy BRCA2-mutation carriers. We thus establish a highly conserved mechanism through which endogenous FA disrupts the GSH-regulated cellular redox homeostasis that is critical during development and aging.

scholarly journals MKP1 phosphatase is recruited by CXCL12 in glioblastoma cells and plays a role in DNA strand breaks repair

2019 ◽  
Vol 41 (4) ◽  
pp. 417-429
Author(s):  
Matthias Dedobbeleer ◽  
Estelle Willems ◽  
Jeremy Lambert ◽  
Arnaud Lombard ◽  
Marina Digregorio ◽  
...  
Keyword(s):  
Dna Repair ◽  
Map Kinases ◽  
Strand Breaks ◽  
Repair Protein ◽  
Map Kinase Phosphatase ◽  
Dna Repair Protein ◽  
The Central Nervous System ◽  
Subventricular Zones ◽  
Dna Strand ◽  
The Brain

Abstract Glioblastoma (GBM) is the most frequent and aggressive primary tumor in the central nervous system. Previously, the secretion of CXCL12 in the brain subventricular zones has been shown to attract GBM cells and protect against irradiation. However, the exact molecular mechanism behind this radioprotection is still unknown. Here, we demonstrate that CXCL12 modulates the phosphorylation of MAP kinases and their regulator, the nuclear MAP kinase phosphatase 1 (MKP1). We further show that MKP1 is able to decrease GBM cell death and promote DNA repair after irradiation by regulating major apoptotic players, such as Jun-N-terminal kinase, and by stabilizing the DNA repair protein RAD51. Increases in MKP1 levels caused by different corticoid treatments should be reexamined for GBM patients, particularly during their radiotherapy sessions, in order to prevent or to delay the relapses of this tumor.

scholarly journals The Development and Decay of the Circadian Clock in Drosophila melanogaster

2019 ◽  
Vol 1 (4) ◽  
pp. 489-500
Author(s):  
Jia Zhao ◽  
Guy Warman ◽  
James Cheeseman
Keyword(s):  
Circadian Clock ◽  
Clock Genes ◽  
Firefly Luciferase ◽  
Whole Body ◽  
Drosophila Model ◽  
Central Clock ◽  
Development And Aging ◽  
Central Oscillator ◽  
The Brain ◽  
Insight Into

The way in which the circadian clock mechanism develops and decays throughout life is interesting for a number of reasons and may give us insight into the process of aging itself. The Drosophila model has been proven invaluable for the study of the circadian clock and development and aging. Here we review the evidence for how the Drosophila clock develops and changes throughout life, and present a new conceptual model based on the results of our recent work. Firefly luciferase lines faithfully report the output of known clock genes at the central clock level in the brain and peripherally throughout the whole body. Our results show that the clock is functioning in embryogenesis far earlier than previously thought. This central clock in the fly remains robust throughout the life of the animal and only degrades immediately prior to death. However, at the peripheral (non-central oscillator level) the clock shows weakened output as the animal ages, suggesting the possibility of the breakdown in the cohesion of the circadian network.

scholarly journals The effect of early-life nutrition on DNA repair and DNA methylation in the brain of newborn piglets

2010 ◽  
Vol 69 (OCE6) ◽  
Author(s):  
S. A. S. Langie ◽  
B. Tomaszewski ◽  
P. Kowalczyk ◽  
R. W. L. Godschalk ◽  
B. Tudek ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Dna Repair ◽  
Early Life ◽  
Newborn Piglets ◽  
The Brain

scholarly journals Vitamin C deficiency in weanling guinea pigs: differential expression of oxidative stress and DNA repair in liver and brain

2007 ◽  
Vol 98 (6) ◽  
pp. 1116-1119 ◽  
Author(s):  
Jens Lykkesfeldt ◽  
Gilberto Perez Trueba ◽  
Henrik E. Poulsen ◽  
Stephan Christen
Keyword(s):  
Oxidative Stress ◽  
Dna Repair ◽  
Vitamin C ◽  
Lipid Oxidation ◽  
Protein Oxidation ◽  
Guinea Pigs ◽  
Vitamin C Deficiency ◽  
Markers Of Oxidative Stress ◽  
Selective Preservation ◽  
The Brain

Neonates are particularly susceptible to malnutrition due to their limited reserves of micronutrients and their rapid growth. In the present study, we examined the effect of vitamin C deficiency on markers of oxidative stress in plasma, liver and brain of weanling guinea pigs. Vitamin C deficiency caused rapid and significant depletion of ascorbate (P < 0·001), tocopherols (P < 0·001) and glutathione (P < 0·001), and a decrease in superoxide dismutase activity (P = 0·005) in the liver, while protein oxidation was significantly increased (P = 0·011). No changes in lipid oxidation or oxidatively damaged DNA were observed in this tissue. In the brain, the pattern was markedly different. Of the measured antioxidants, only ascorbate was significantly depleted (P < 0·001), but in contrast to the liver, ascorbate oxidation (P = 0·034), lipid oxidation (P < 0·001), DNA oxidation (P = 0·13) and DNA incision repair (P = 0·014) were all increased, while protein oxidation decreased (P = 0·003). The results show that the selective preservation of brain ascorbate and induction of DNA repair in vitamin C-deficient weanling guinea pigs is not sufficient to prevent oxidative damage. Vitamin C deficiency may therefore be particularly adverse during the neonatal period.

Effect of androgens on the brain and other organs during development and aging

1992 ◽  
Vol 17 (4) ◽  
pp. 375-383 ◽  
Author(s):  
Ronald S. Swerdloff ◽  
Christina Wang ◽  
Melissa Hines ◽  
Roger Gorski
Keyword(s):  
Development And Aging ◽  
The Brain

scholarly journals The Role of Gut Microbiota in an Ischemic Stroke

2021 ◽  
Vol 22 (2) ◽  
pp. 915
Author(s):  
Ryszard Pluta ◽  
Sławomir Januszewski ◽  
Stanisław J. Czuczwar
Keyword(s):  
Ischemic Stroke ◽  
Intestinal Microflora ◽  
Intestinal Bacteria ◽  
Intestinal Microbiome ◽  
Gut Dysfunction ◽  
Development And Aging ◽  
Host Metabolism ◽  
The Impact ◽  
The Brain

The intestinal microbiome, the largest reservoir of microorganisms in the human body, plays an important role in neurological development and aging as well as in brain disorders such as an ischemic stroke. Increasing knowledge about mediators and triggered pathways has contributed to a better understanding of the interaction between the gut-brain axis and the brain-gut axis. Intestinal bacteria produce neuroactive compounds and can modulate neuronal function, which affects behavior after an ischemic stroke. In addition, intestinal microorganisms affect host metabolism and immune status, which in turn affects the neuronal network in the ischemic brain. Here we discuss the latest results of animal and human research on two-way communication along the gut-brain axis in an ischemic stroke. Moreover, several reports have revealed the impact of an ischemic stroke on gut dysfunction and intestinal dysbiosis, highlighting the delicate play between the brain, intestines and microbiome after this acute brain injury. Despite our growing knowledge of intestinal microflora in shaping brain health, host metabolism, the immune system and disease progression, its therapeutic options in an ischemic stroke have not yet been fully utilized. This review shows the role of the gut microflora-brain axis in an ischemic stroke and assesses the potential role of intestinal microflora in the onset, progression and recovery post-stroke.

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