scholarly journals High intensity muscle stimulation activates a systemic Nrf2-mediated redox stress response

Author(s):  
Ethan L. Ostrom ◽  
Ana P. Valencia ◽  
David J. Marcinek ◽  
Tinna Traustadóttir
2021 ◽  
Author(s):  
Ethan L. Ostrom ◽  
Ana P. Valencia ◽  
David J. Marcinek ◽  
Tinna Traustadóttir

ABSTRACTIntroductionHigh intensity exercise is an increasingly popular mode of exercise to elicit similar or greater adaptive responses compared to traditional moderate intensity continuous exercise. However, the molecular mechanisms underlying these adaptive responses are still unclear. The purpose of this pilot study was to compare high and low intensity contractile stimulus on the Nrf2-mediated redox stress response in mouse skeletal muscle.MethodsAn intra-animal design was used to control for variations in individual responses to muscle stimulation by using a stimulated limb (STIM) and comparing to the contralateral unstimulated control limb (CON). High Intensity (HI – 100Hz), Low Intensity (LI – 50Hz), and Naïve Control (NC – Mock stimulation vs CON) groups were used to compare these effects on Nrf2-ARE binding, Keap1 protein content, and downstream gene and protein expression of Nrf2 target genes.ResultsMuscle stimulation significantly increased Nrf2-ARE binding in LI-STIM compared to LI-CON (p = 0.0098), while Nrf2-ARE binding was elevated in both HI-CON and HI-STIM compared to NC (p = 0.0007). The Nrf2-ARE results were mirrored in the downregulation of Keap1, where Keap1 expression in HI-CON and HI-STIM were both significantly lower than NC (p = 0.008) and decreased in LI-STIM compared to LI-CON (p = 0.015). In addition, stimulation increased NQO1 protein compared to contralateral control regardless of stimulation intensity (p = 0.019).ConclusionsTaken together, these data suggest a systemic redox signaling exerkine is activating Nrf2-ARE binding and is intensity gated, where Nrf2-ARE activation in contralateral control limbs were only seen in the HI group. Other research in exercise induced Nrf2 signaling support the general finding that Nrf2 is activated in peripheral tissues in response to exercise, however the specific exerkine responsible for the systemic signaling effects is not known. Future work should aim to delineate these redox sensitive systemic signaling mechanisms.


2011 ◽  
Vol 43 (Suppl 1) ◽  
pp. 905-906
Author(s):  
Michael J. Ormsbee ◽  
Amber W. Kinsey ◽  
Minwook Chong ◽  
Heather S. Friedman ◽  
Tonya Dodge ◽  
...  

2014 ◽  
Vol 197 (5) ◽  
pp. 913-923 ◽  
Author(s):  
François Daigle ◽  
Sylvain Lerat ◽  
Giselda Bucca ◽  
Édith Sanssouci ◽  
Colin P. Smith ◽  
...  

AlthoughStreptomyces coelicoloris not resistant to tellurite, it possesses several TerD domain-encoding (tdd) genes of unknown function. To elucidate the function oftdd8, the transcriptomes ofS. coelicolorstrain M145 and of atdd8deletion mutant derivative (the Δtdd8strain) were compared. Several orthologs ofMycobacterium tuberculosisgenes involved in dormancy survival were upregulated in the deletion mutant at the visual onset of prodiginine production. These genes are organized in a putative redox stress response cluster comprising two large loci. A binding motif similar to the dormancy survival regulator (DosR) binding site ofM. tuberculosishas been identified in the upstream sequences of most genes in these loci. A predicted role for these genes in the redox stress response is supported by the low NAD+/NADH ratio in the Δtdd8strain. ThisS. coelicolorgene cluster was shown to be induced by hypoxia and NO stress. While thetdd8deletion mutant (the Δtdd8strain) was unable to maintain calcium homeostasis in a calcium-depleted medium, the addition of Ca2+in Δtdd8culture medium reduced the expression of several genes of the redox stress response cluster. The results shown in this work are consistent with Tdd8 playing a significant role in calcium homeostasis and redox stress adaptation.


2021 ◽  
Author(s):  
Harsh Goar ◽  
Partha Paul ◽  
Hina Khan ◽  
Dibyendu SARKAR

The main purpose of this study is to understand how mycobacteria can sense numerous stress conditions and mount an appropriate stress response. Recent studies suggest that at low pH M. tuberculosis encounters reductive stress, and in response, modulates redox homeostasis by utilizing the phoPR regulatory system. However, the mechanism of integrated regulation of stress response remains unknown. To probe how PhoP contributes to redox stress response, we find that a PhoP-depleted M. tuberculosis shows a significantly enhanced susceptibility to redox stress relative to the WT bacilli. In keeping with these results, PhoP was shown to contribute to mycothiol redox state. Because SigH, one of the alternative sigma factors of mycobacteria, is known to control expression of redox inducible genes, we probed whether previously-reported PhoP-SigH interaction accounts for mycobacterial redox stress response. We had shown that under acidic conditions PhoP functions in maintaining pH homeostasis via its interaction with SigE. In striking contrast, here we show that under redox stress, direct recruitment of SigH, but not PhoP-SigH interaction, controls expression of mycobacterial thioredoxin genes, a major mycobacterial anti-oxidant system. Together, these unexpected results uncover novel stress-specific enhanced or reduced interaction events of sigma factors and PhoP, as the underlying mechanisms of an adaptive programme, which couples low pH conditions and mycobacterial thiol redox homeostasis.


PLoS ONE ◽  
2014 ◽  
Vol 9 (1) ◽  
pp. e87506 ◽  
Author(s):  
Alessandra Vezzoli ◽  
Lorenzo Pugliese ◽  
Mauro Marzorati ◽  
Fabio Rubens Serpiello ◽  
Antonio La Torre ◽  
...  

PLoS ONE ◽  
2017 ◽  
Vol 12 (1) ◽  
pp. e0171247 ◽  
Author(s):  
Andrzej Kochanowicz ◽  
Stanisław Sawczyn ◽  
Bartłomiej Niespodziński ◽  
Jan Mieszkowski ◽  
Kazimierz Kochanowicz ◽  
...  

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