scholarly journals Chronic Variable Stress Is Responsible for Lipid and DNA Oxidative Disorders and Activation of Oxidative Stress Response Genes in the Brain of Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Mariola Herbet ◽  
Agnieszka Korga ◽  
Monika Gawrońska-Grzywacz ◽  
Magdalena Izdebska ◽  
Iwona Piątkowska-Chmiel ◽  
...  

Chronic environmental stress is associated with reactive oxygen species (ROS) overproduction and the pathogenesis of depression. The purpose of this study was to evaluate biochemical and molecular changes associated with ROS generation in the brains of rats submitted to chronic variable stress. Male Wistar rats (50–55 days old, weighing 200–250 g) were divided in two groups (n=10): control and stressed. Rats in the stressed group were exposed to stress conditions for 40 days. The animals were decapitated and the brain samples were collected. In prefrontal cortex, we measured the following biochemical parameters: lipid peroxidation and concentration of glutathione—GSH, GSSG, GSH/GSSG ratio, glutathione peroxidase, and glutathione reductase activities. In the hippocampus marker of DNA, oxidative damage and expression of DNA-repairing genes (Ogg1,MsrA) and gene-encoding antioxidative transcriptional factor (Nrf2) were determined. The results demonstrate indirect evidence of ROS overproduction and presence of oxidative stress. They also reveal disruption of oxidative defense systems (decreased GR activity, diminished GSH/GSSG ratio, and decreasedNrf2expression) and activation of the oxidative DNA repair system (increasedOgg1andMsrAexpression). Together, the presented data suggest that independent activation of oxidative stress response genes occurs in chronic variable stress conditions.

Oncotarget ◽  
2013 ◽  
Vol 4 (12) ◽  
pp. 2577-2590 ◽  
Author(s):  
Barak Rotblat ◽  
Thomas G. P. Grunewald ◽  
Gabriel Leprivier ◽  
Gerry Melino ◽  
Richard A. Knight

2019 ◽  
Author(s):  
Zhuo Ma ◽  
Kayla King ◽  
Maha Alqahtani ◽  
Madeline Worden ◽  
Parthasarthy Muthuraman ◽  
...  

AbstractFrancisella tularensis is a Gram-negative bacterium responsible for causing tularemia in the northern hemisphere. F. tularensis has long been developed as a biological weapon due to its ability to cause severe illness upon inhalation of as few as ten organisms and based on its potential to be used as a bioterror agent is now classified as a Tier 1 Category A select agent by the CDC. The stringent response facilitates bacterial survival under nutritionally challenging starvation conditions. The hallmark of stringent response is the accumulation of the effector molecules ppGpp and (p)ppGpp known as stress alarmones. The relA and spoT gene products generate alarmones in several Gram-negative bacterial pathogens. RelA is a ribosome-associated ppGpp synthetase that gets activated under amino acid starvation conditions whereas, SpoT is a bifunctional enzyme with both ppGpp synthetase and ppGpp hydrolase activities. Francisella encodes a monofunctional RelA and a bifunctional SpoT enzyme. Previous studies have demonstrated that stringent response under nutritional stresses increases expression of virulence-associated genes encoded on Francisella Pathogenicity Island. This study investigated how stringent response governs the oxidative stress response of F. tularensis. We demonstrate that RelA/SpoT-mediated ppGpp production alters global gene transcriptional profile of F. tularensis in the presence of oxidative stress. The lack of stringent response in relA/spoT gene deletion mutants of F. tularensis makes bacteria more susceptible to oxidants, attenuates survival in macrophages, and virulence in mice. Mechanistically, we provide evidence that the stringent response in Francisella contributes to oxidative stress resistance by enhancing the production of antioxidant enzymes.ImportanceThe unique intracellular life cycle of Francisella in addition to nutritional stress also exposes the bacteria to oxidative stress conditions upon its brief residence in the phagosomes, and escape into the cytosol where replication takes place. However, the contribution of the stringent response in gene regulation and management of the oxidative stress response when Francisella is experiencing oxidative stress conditions is not known. Our results provide a link between the stringent and oxidative stress responses. This study further improves our understanding of the intracellular survival mechanisms of F. tularensis.


2008 ◽  
Vol 40 (Supplement) ◽  
pp. S476 ◽  
Author(s):  
Kimberly A. Sewright ◽  
Maria L. Urso ◽  
Paul D. Thompson ◽  
Cherie Bilbe ◽  
Yi-Wen Chen ◽  
...  

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