scholarly journals Decrease in Manganese Superoxide Dismutase Leads to Reduced Root Growth and Affects Tricarboxylic Acid Cycle Flux and Mitochondrial Redox Homeostasis

2008 ◽  
Vol 147 (1) ◽  
pp. 101-114 ◽  
Author(s):  
Megan J. Morgan ◽  
Martin Lehmann ◽  
Markus Schwarzländer ◽  
Charles J. Baxter ◽  
Agata Sienkiewicz-Porzucek ◽  
...  
2020 ◽  
Author(s):  
Mario L. Arrieta-Ortiz ◽  
Min Pan ◽  
Amardeep Kaur ◽  
Vivek Srinivas ◽  
Ananya Dash ◽  
...  

ABSTRACTThere is an urgent need for strategies to discover secondary drugs to prevent or disrupt antimicrobial resistance (AMR), which is causing >700,000 deaths annually. Here, we demonstrate that tetracycline resistant (TetR) Escherichia coli undergoes global transcriptional and metabolic remodeling, including down-regulation of tricarboxylic acid cycle and disruption of redox homeostasis, to support consumption of the proton motive force for tetracycline efflux. Targeted knockout of ArcA, identified by network analysis as a master regulator among 25 transcription factors of this new compensatory physiological state, significantly increased the susceptibility of TetRE. coli to tetracycline treatment. A drug, sertraline, which generated a similar metabolome profile as the arcA knockout strain also synergistically re-sensitized TetRE. coli to tetracycline. The potentiating effect of sertraline was eliminated upon knocking out arcA, demonstrating that the mechanism of synergy was through action of sertraline on the tetracycline-induced ArcA network in the TetR strain. Our findings demonstrate that targeting mechanistic drivers of compensatory physiological states could be a generalizable strategy to re-sensitize AMR pathogens to lost antibiotics.


2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Chang Li ◽  
Hai-Meng Zhou

Antioxidant enzymes maintain cellular redox homeostasis. Manganese superoxide dismutase (MnSOD), an enzyme located in mitochondria, is the key enzyme that protects the energy-generating mitochondria from oxidative damage. Levels of MnSOD are reduced in many diseases, including cancer, neurodegenerative diseases, and psoriasis. Overexpression of MnSOD in tumor cells can significantly attenuate the malignant phenotype. Past studies have reported that this enzyme has the potential to be used as an anti-inflammatory agent because of its superoxide anion scavenging ability. Superoxide anions have a proinflammatory role in many diseases. Treatment of a rat model of lung pleurisy with the MnSOD mimetic MnTBAP suppressed the inflammatory response in a dose-dependent manner. In this paper, the mechanisms underlying the suppressive effects of MnSOD in inflammatory diseases are studied, and the potential applications of this enzyme and its mimetics as anti-inflammatory agents are discussed.


2010 ◽  
Vol 153 (2) ◽  
pp. 611-621 ◽  
Author(s):  
Margaretha J. van der Merwe ◽  
Sonia Osorio ◽  
Wagner L. Araújo ◽  
Ilse Balbo ◽  
Adriano Nunes-Nesi ◽  
...  

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yiyong Wei ◽  
Donghang Zhang ◽  
Jin Liu ◽  
Mengchan Ou ◽  
Peng Liang ◽  
...  

Abstract Background Metabolic status can be impacted by general anesthesia and surgery. However, the exact effects of general anesthesia and surgery on systemic metabolome remain unclear, which might contribute to postoperative outcomes. Methods Five hundred patients who underwent abdominal surgery were included. General anesthesia was mainly maintained with sevoflurane. The end-tidal sevoflurane concentration (ETsevo) was adjusted to maintain BIS (Bispectral index) value between 40 and 60. The mean ETsevo from 20 min after endotracheal intubation to 2 h after the beginning of surgery was calculated for each patient. The patients were further divided into low ETsevo group (mean − SD) and high ETsevo group (mean + SD) to investigate the possible metabolic changes relevant to the amount of sevoflurane exposure. Results The mean ETsevo of the 500 patients was 1.60% ± 0.34%. Patients with low ETsevo (n = 55) and high ETsevo (n = 59) were selected for metabolomic analysis (1.06% ± 0.13% vs. 2.17% ± 0.16%, P < 0.001). Sevoflurane and abdominal surgery disturbed the tricarboxylic acid cycle as identified by increased citrate and cis-aconitate levels and impacted glycometabolism as identified by increased sucrose and D-glucose levels in these 114 patients. Glutamate metabolism was also impacted by sevoflurane and abdominal surgery in all the patients. In the patients with high ETsevo, levels of L-glutamine, pyroglutamic acid, sphinganine and L-selenocysteine after sevoflurane anesthesia and abdominal surgery were significantly higher than those of the patients with low ETsevo, suggesting that these metabolic changes might be relevant to the amount of sevoflurane exposure. Conclusions Sevoflurane anesthesia and abdominal surgery can impact principal metabolic pathways in clinical patients including tricarboxylic acid cycle, glycometabolism and glutamate metabolism. This study may provide a resource data for future studies about metabolism relevant to general anaesthesia and surgeries. Trial registration www.chictr.org.cn. identifier: ChiCTR1800014327.


Sign in / Sign up

Export Citation Format

Share Document